Sample records for active muscle fibers

  1. Functional characteristics of the rat jaw muscles: daily muscle activity and fiber type composition.

    PubMed

    Kawai, Nobuhiko; Sano, Ryota; Korfage, Joannes A M; Nakamura, Saika; Tanaka, Eiji; van Wessel, Tim; Langenbach, Geerling E J; Tanne, Kazuo

    2009-12-01

    Skeletal muscles have a heterogeneous fiber type composition, which reflects their functional demand. The daily muscle use and the percentage of slow-type fibers have been shown to be positively correlated in skeletal muscles of larger animals but for smaller animals there is no information. The examination of this relationship in adult rats was the purpose of this study. We hypothesized a positive relationship between the percentage of fatigue-resistant fibers in each muscle and its total duration of use per day. Fourteen Wistar strain male rats (410-450 g) were used. A radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter, deep masseter, anterior belly of digastric and anterior temporalis muscles. The degree of daily muscle use was quantified by the total duration of muscle activity per day (duty time) exceeding specified levels of the peak activity (2, 5, 20 and 50%). The fiber type composition of the muscles was examined by the myosin heavy chain content of the fibers by means of immunohistochemical staining. At lower activity levels (exceeding 2 and 5% of the peak activity), the duty time of the anterior belly of digastric muscle was significantly (P < 0.01) longer than those of the other muscles. The anterior belly of digastric muscle also contained the highest percentage of slow-type fibers (type I fiber and hybrid fiber co-expressing myosin heavy chain I + IIA) (ca. 11%; P < 0.05). By regression analysis for all four muscles, an inter-muscular comparison showed a positive relationship between the duty time (exceeding 50% of the peak activity) and the percentage of type IIX fibers (P < 0.05), which demonstrate intermediate physiological properties relative to type IIA and IIB fibers. For the jaw muscles of adult male rats, the variations of fiber type composition and muscle use suggest that the muscle containing the largest amounts of slow-type fibers (the anterior belly of digastric muscle) is mainly

  2. Effect of altering starting length and activation timing of muscle on fiber strain and muscle damage.

    PubMed

    Butterfield, Timothy A; Herzog, Walter

    2006-05-01

    Muscle strain injuries are some of the most frequent injuries in sports and command a great deal of attention in an effort to understand their etiology. These injuries may be the culmination of a series of subcellular events accumulated through repetitive lengthening (eccentric) contractions during exercise, and they may be influenced by a variety of variables including fiber strain magnitude, peak joint torque, and starting muscle length. To assess the influence of these variables on muscle injury magnitude in vivo, we measured fiber dynamics and joint torque production during repeated stretch-shortening cycles in the rabbit tibialis anterior muscle, at short and long muscle lengths, while varying the timing of activation before muscle stretch. We found that a muscle subjected to repeated stretch-shortening cycles of constant muscle-tendon unit excursion exhibits significantly different joint torque and fiber strains when the timing of activation or starting muscle length is changed. In particular, measures of fiber strain and muscle injury were significantly increased by altering activation timing and increasing the starting length of the muscle. However, we observed differential effects on peak joint torque during the cyclic stretch-shortening exercise, as increasing the starting length of the muscle did not increase torque production. We conclude that altering activation timing and muscle length before stretch may influence muscle injury by significantly increasing fiber strain magnitude and that fiber dynamics is a more important variable than muscle-tendon unit dynamics and torque production in influencing the magnitude of muscle injury.

  3. Muscle Activation During Peripheral Nerve Field Stimulation Occurs Due to Recruitment of Efferent Nerve Fibers, Not Direct Muscle Activation.

    PubMed

    Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

    2016-08-01

    Peripheral nerve field stimulation (PNFS) is a potential treatment for chronic low-back pain. Pain relief using PNFS is dependent on activation of non-nociceptive Aβ-fibers. However, PNFS may also activate muscles, causing twitches and discomfort. In this study, we developed a mathematical model, to investigate the activation of sensory and motor nerves, as well as direct muscle fiber activation. The extracellular field was estimated using a finite element model based on the geometry of CT scanned lumbar vertebrae. The electrode was modeled as being implanted to a depth of 10-15 mm. Three implant directions were modeled; horizontally, vertically, and diagonally. Both single electrode and "between-lead" stimulation between contralateral electrodes were modeled. The extracellular field was combined with models of sensory Aβ-nerves, motor neurons and muscle fibers to estimate their activation thresholds. The model showed that sensory Aβ fibers could be activated with thresholds down to 0.563 V, and the lowest threshold for motor nerve activation was 7.19 V using between-lead stimulation with the cathode located closest to the nerves. All thresholds for direct muscle activation were above 500 V. The results suggest that direct muscle activation does not occur during PNFS, and concomitant motor and sensory nerve fiber activation are only likely to occur when using between-lead configuration. Thus, it may be relevant to investigate the location of the innervation zone of the low-back muscles prior to electrode implantation to avoid muscle activation. © 2016 International Neuromodulation Society.

  4. Is fast fiber innervation responsible for increased acetylcholinesterase activity in reinnervating soleus muscles?

    NASA Technical Reports Server (NTRS)

    Misulis, K. E.; Dettbarn, W. D.

    1985-01-01

    An investigation was conducted as to whether the predominantly slow SOL, which is low in AChE activity, is initially reinnervated by axons that originally innervated fast muscle fibers with high AChE activity, such as those of the EDL. Local denervation of the SOL in the guinea pig was performed because this muscle is composed solely of slow (type I) fibers; thereby virtually eliminating the possibility of homologous muscle fast fiber innervation. The overshoot in this preparation was qualitatively similar to that seen with distal denervation in the guinea pig and local and distal denervation in the rat. Thus, initial fast fiber innvervation is not responsible for the patterns of change in AChE activity seen with reinnervation in the SOL. It is concluded that the neural control of AChe is different in these two muscles and may reflect specific differences in the characteristics of AChE regulation in fast and slow muscle.

  5. Modulation of skeletal muscle fiber type by mitogen-activated protein kinase signaling.

    PubMed

    Shi, Hao; Scheffler, Jason M; Pleitner, Jonathan M; Zeng, Caiyun; Park, Sungkwon; Hannon, Kevin M; Grant, Alan L; Gerrard, David E

    2008-08-01

    Skeletal muscle is composed of diverse fiber types, yet the underlying molecular mechanisms responsible for this diversification remain unclear. Herein, we report that the extracellular signal-regulated kinase (ERK) 1/2 pathway, but not p38 or c-Jun NH(2)-terminal kinase (JNK), is preferentially activated in fast-twitch muscles. Pharmacological blocking of ERK1/2 pathway increased slow-twitch fiber type-specific reporter activity and repressed those associated with the fast-twitch fiber phenotype in vitro. Overexpression of a constitutively active ERK2 had an opposite effect. Inhibition of ERK signaling in cultured myotubes increased slow-twitch fiber-specific protein accumulation while repressing those characteristic of fast-twitch fibers. Overexpression of MAP kinase phosphatase-1 (MKP1) in mouse and rat muscle fibers containing almost exclusively type IIb or IIx fast myosin heavy chain (MyHC) isoforms induced de novo synthesis of the slower, more oxidative type IIa and I MyHCs in a time-dependent manner. Conversion to the slower phenotype was confirmed by up-regulation of slow reporter gene activity and down-regulation of fast reporter activities in response to forced MKP1 expression in vivo. In addition, activation of ERK2 signaling induced up-regulation of fast-twitch fiber program in soleus. These data suggest that the MAPK signaling, most likely the ERK1/2 pathway, is necessary to preserve the fast-twitch fiber phenotype with a concomitant repression of slow-twitch fiber program.

  6. Age-related changes in rat intrinsic laryngeal muscles: analysis of muscle fibers, muscle fiber proteins, and subneural apparatuses.

    PubMed

    Nishida, Naoya; Taguchi, Aki; Motoyoshi, Kazumi; Hyodo, Masamitsu; Gyo, Kiyofumi; Desaki, Junzo

    2013-03-01

    We compared age-related changes in the intrinsic laryngeal muscles of aged and young adult rats by determining the number and diameter of muscle fibers, contractile muscle protein (myosin heavy chain isoforms, MHC) composition, and the morphology of the subneural apparatuses. In aged rats, both the numbers and the diameters of muscle fibers decreased in the cricothyroid (CT) muscle. The number of fibers, but not diameter, decreased in the thyroarytenoid (TA) muscle. In the posterior cricoarytenoid (PCA) muscle, neither the number nor the diameter of fibers changed significantly. Aging was associated with a decrease in type IIB and an increase in type IIA MHC isoform levels in CT muscle, but no such changes were observed in the TA or PCA muscles. Morphological examination of primary synaptic clefts of the subneural apparatus revealed that aging resulted in decreased labyrinthine and increased depression types in only the CT muscle. In the aged group, morphologically immature subneural apparatuses were found infrequently in the CT muscle, indicating continued tissue remodeling. We suggest, therefore, that age-related changes in the intrinsic laryngeal muscles primarily involve the CT muscle, whereas the structures of the TA and PCA muscles may better resist aging processes and therefore are less vulnerable to functional impairment. This may reflect differences in their roles; the CT muscle controls the tone of the vocal folds, while the TA and PCA muscles play an essential role in vital activities such as respiration and swallowing.

  7. Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.

    PubMed

    Mendias, Christopher L; Schwartz, Andrew J; Grekin, Jeremy A; Gumucio, Jonathan P; Sugg, Kristoffer B

    2017-03-01

    Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sF o ), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point. NEW & NOTEWORTHY This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic

  8. Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy

    PubMed Central

    Schwartz, Andrew J.; Grekin, Jeremy A.; Gumucio, Jonathan P.; Sugg, Kristoffer B.

    2017-01-01

    Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7, and 28 days after induction of hypertrophy, and nonoverloaded rats served as controls. Muscle fiber specific force (sFo), which is the maximum isometric force normalized to cross-sectional area, was reduced 3 and 7 days after the onset of mechanical overload, but returned to control levels by 28 days. Collagen abundance displayed a similar pattern of change. Nearly a quarter of the transcriptome changed over the course of overload, as well as the activation of signaling pathways related to hypertrophy and atrophy. Overall, this study provides insight into fundamental mechanisms of muscle and ECM growth, and indicates that although muscle fibers appear to have completed remodeling and regeneration 1 mo after synergist ablation, the ECM continues to be actively remodeling at this time point. NEW & NOTEWORTHY This study utilized a rat synergist ablation model to integrate changes in single muscle fiber contractility, extracellular matrix composition, activation of important signaling pathways in muscle adaption, and corresponding changes in the muscle transcriptome to provide novel insight into the basic

  9. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy

    PubMed Central

    Reed, Sarah A.; Sandesara, Pooja B.; Senf, Sarah M.; Judge, Andrew R.

    2012-01-01

    Cachexia is characterized by inexorable muscle wasting that significantly affects patient prognosis and increases mortality. Therefore, understanding the molecular basis of this muscle wasting is of significant importance. Recent work showed that components of the forkhead box O (FoxO) pathway are increased in skeletal muscle during cachexia. In the current study, we tested the physiological significance of FoxO activation in the progression of muscle atrophy associated with cachexia. FoxO-DNA binding dependent transcription was blocked in the muscles of mice through injection of a dominant negative (DN) FoxO expression plasmid prior to inoculation with Lewis lung carcinoma cells or the induction of sepsis. Expression of DN FoxO inhibited the increased mRNA levels of atrogin-1, MuRF1, cathepsin L, and/or Bnip3 and inhibited muscle fiber atrophy during cancer cachexia and sepsis. Interestingly, during control conditions, expression of DN FoxO decreased myostatin expression, increased MyoD expression and satellite cell proliferation, and induced fiber hypertrophy, which required de novo protein synthesis. Collectively, these data show that FoxO-DNA binding-dependent transcription is necessary for normal muscle fiber atrophy during cancer cachexia and sepsis, and further suggest that basal levels of FoxO play an important role during normal conditions to depress satellite cell activation and limit muscle growth.—Reed, S. A., Sandesara, P. B., Senf, S. F., Judge, A. R. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. PMID:22102632

  10. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy

    PubMed Central

    Fry, Christopher S.; Lee, Jonah D.; Jackson, Janna R.; Kirby, Tyler J.; Stasko, Shawn A.; Liu, Honglu; Dupont-Versteegden, Esther E.; McCarthy, John J.; Peterson, Charlotte A.

    2014-01-01

    Our aim in the current study was to determine the necessity of satellite cells for long-term muscle growth and maintenance. We utilized a transgenic Pax7-DTA mouse model, allowing for the conditional depletion of > 90% of satellite cells with tamoxifen treatment. Synergist ablation surgery, where removal of synergist muscles places functional overload on the plantaris, was used to stimulate robust hypertrophy. Following 8 wk of overload, satellite cell-depleted muscle demonstrated an accumulation of extracellular matrix (ECM) and fibroblast expansion that resulted in reduced specific force of the plantaris. Although the early growth response was normal, an attenuation of hypertrophy measured by both muscle wet weight and fiber cross-sectional area occurred in satellite cell-depleted muscle. Isolated primary myogenic progenitor cells (MPCs) negatively regulated fibroblast ECM mRNA expression in vitro, suggesting a novel role for activated satellite cells/MPCs in muscle adaptation. These results provide evidence that satellite cells regulate the muscle environment during growth.—Fry, C. S., Lee, J. D., Jackson, J. R., Kirby, T. J., Stasko, S. A., Liu, H., Dupont-Versteegden, E. E., McCarthy, J. J., Peterson, C. A. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy. PMID:24376025

  11. Single muscle fiber adaptations with marathon training.

    PubMed

    Trappe, Scott; Harber, Matthew; Creer, Andrew; Gallagher, Philip; Slivka, Dustin; Minchev, Kiril; Whitsett, David

    2006-09-01

    The purpose of this investigation was to characterize the effects of marathon training on single muscle fiber contractile function in a group of recreational runners. Muscle biopsies were obtained from the gastrocnemius muscle of seven individuals (22 +/- 1 yr, 177 +/- 3 cm, and 68 +/- 2 kg) before, after 13 wk of run training, and after 3 wk of taper. Slow-twitch myosin heavy chain [(MHC) I] and fast-twitch (MHC IIa) muscle fibers were analyzed for size, strength (P(o)), speed (V(o)), and power. The run training program led to the successful completion of a marathon (range 3 h 56 min to 5 h 35 min). Oxygen uptake during submaximal running and citrate synthase activity were improved (P < 0.05) with the training program. Muscle fiber size declined (P < 0.05) by approximately 20% in both fiber types after training. P(o) was maintained in both fiber types with training and increased (P < 0.05) by 18% in the MHC IIa fibers after taper. This resulted in >60% increase (P < 0.05) in force per cross-sectional area in both fiber types. Fiber V(o) increased (P < 0.05) by 28% in MHC I fibers with training and was unchanged in MHC IIa fibers. Peak power increased (P < 0.05) in MHC I and IIa fibers after training with a further increase (P < 0.05) in MHC IIa fiber power after taper. These data show that marathon training decreased slow-twitch and fast-twitch muscle fiber size but that it maintained or improved the functional profile of these fibers. A taper period before the marathon further improved the functional profile of the muscle, which was targeted to the fast-twitch muscle fibers.

  12. Muscle fiber-type conversion in the transgenic pigs with overexpression of PGC1α gene in muscle.

    PubMed

    Ying, Fei; Zhang, Liang; Bu, Guowei; Xiong, Yuanzhu; Zuo, Bo

    2016-11-25

    The peroxisome proliferator-activated receptor gamma, co-activator 1 alpha(PGC1α) effectively induced the biosynthesis of the mitochondria and the energy metabolism, and also regulated the muscle fiber-type shift. Overexpression of PGC1α gene in mice led to higher oxidative muscle fiber composition in muscle. However, no researches about the significant differences of muscle fiber phenotype in pigs after PGC1α overexpression had been reported. The composition of muscle fiber-types which were distinguished by four myosin heavy chain(MYHC) isoforms, can significantly affect the muscle functions. In our study, we generated the transgenic pigs to investigate the effect of overexpression of PGC1α gene on muscle fiber-type conversion. The results showed that the number of oxidative muscle fiber(type1 muscle fiber) was increased and the number of glycolytic muscle fiber(type2b muscle fiber) was decreased in the transgenic pigs. Furthermore, we found that PGC1α overexpression up-regulated the expression of MYHC1 and MYHC2a and down-regulated the expression of MYHC2b.The analysis of genes expression demonstrated the main differentially expressed genes were MSTN, Myog and FOXO1. In conclusion, the overexpression of PGC1α gene can promote the glycolytic muscle fiber transform to the oxidative muscle fiber in pigs. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Muscle fiber-type conversion in the transgenic pigs with overexpression of PGC1α gene in muscle

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ying, Fei; Zhang, Liang; Bu, Guowei

    The peroxisome proliferator-activated receptor gamma, co-activator 1 alpha(PGC1α) effectively induced the biosynthesis of the mitochondria and the energy metabolism, and also regulated the muscle fiber-type shift. Overexpression of PGC1α gene in mice led to higher oxidative muscle fiber composition in muscle. However, no researches about the significant differences of muscle fiber phenotype in pigs after PGC1α overexpression had been reported. The composition of muscle fiber-types which were distinguished by four myosin heavy chain(MYHC) isoforms, can significantly affect the muscle functions. In our study, we generated the transgenic pigs to investigate the effect of overexpression of PGC1α gene on muscle fiber-typemore » conversion. The results showed that the number of oxidative muscle fiber(type1 muscle fiber) was increased and the number of glycolytic muscle fiber(type2b muscle fiber) was decreased in the transgenic pigs. Furthermore, we found that PGC1α overexpression up-regulated the expression of MYHC1 and MYHC2a and down-regulated the expression of MYHC2b.The analysis of genes expression demonstrated the main differentially expressed genes were MSTN, Myog and FOXO1. In conclusion, the overexpression of PGC1α gene can promote the glycolytic muscle fiber transform to the oxidative muscle fiber in pigs.« less

  14. Muscle Fiber Types and Training.

    ERIC Educational Resources Information Center

    Karp, Jason R.

    2001-01-01

    The specific types of fibers that make up individual muscles greatly influence how people will adapt to their training programs. This paper explains the complexities of skeletal muscles, focusing on types of muscle fibers (slow-twitch and fast-twitch), recruitment of muscle fibers to perform a motor task, and determining fiber type. Implications…

  15. Cycle Training Increased GLUT4 and Activation of mTOR in Fast Twitch Muscle Fibers

    PubMed Central

    Stuart, Charles A.; Howell, Mary E.A.; Baker, Jonathan D.; Dykes, Rhesa J.; Duffourc, Michelle M.; Ramsey, Michael W.; Stone, Michael H.

    2009-01-01

    Purpose To determine if cycle training of sedentary subjects would increase the expression of the principle muscle glucose transporters, six volunteers completed six weeks of progressively increasing intensity stationary cycle cycling. Methods In vastus lateralis muscle biopsies, changes in expression of GLUT1, GLUT4, GLUT5, and GLUT12 were compared using quantitative immunoblots with specific protein standards. Regulatory pathway components were evaluated by immunoblots of muscle homogenates and immunohistochemistry of microscopic sections. Results GLUT1 was unchanged, GLUT4 increased 66%, GLUT12 increased 104%, and GLUT5 decreased 72%. A mitochondrial marker (cytochrome c) and regulators of mitochondrial biogenesis (PGC-1α and phospho-AMPK) were unchanged, but the muscle hypertrophy pathway component, phospho-mTOR increased 83% after the exercise program. In baseline biopsies, GLUT4 by immunohistochemical techniques was 37% greater in Type I (slow twitch, red) muscle fibers, but the exercise training increased GLUT4 expression in Type II (fast twitch, white) fibers by 50%, achieving parity with the Type I fibers. Baseline phospho-mTOR expression was 50% higher in Type II fibers and increased more in Type II fibers (62%) with training, but also increased in Type I fibers (34%). Conclusion Progressive intensity stationary cycle training of previously sedentary subjects increased muscle insulin-responsive glucose transporters (GLUT4 and GLUT12) and decreased the fructose transporter (GLUT5). The increase in GLUT4 occurred primarily in Type II muscle fibers and this coincided with activation of the mTOR muscle hypertrophy pathway. There was little impact on Type I fiber GLUT4 expression and no evidence of change in mitochondrial biogenesis. PMID:20010125

  16. Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

    NASA Technical Reports Server (NTRS)

    Rosenthal, Nadia A.

    1999-01-01

    The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as

  17. Adaptations of human skeletal muscle fibers to spaceflight

    NASA Technical Reports Server (NTRS)

    Day, M. Kathleen; Allen, David L.; Mohajerani, Laleh; Greenisen, Michael C.; Roy, Roland R.; Edgerton, V. Reggie

    1995-01-01

    Human skeletal muscle fibers seem to share most of the same interrelationships among myosin ATPase activity, myosin heavy chain (MHC) phenotype, mitochondrial enzyme activities, glycolytic enzyme activities, and cross-sectional area (CSA) as found in rat, cat, and other species. One difference seems to be that fast fibers with high mitochrondrial content occur less frequently in humans than in the rat or cat. Recently, we have reported that the type of MHC expressed and the size of the muscle fibers in humans that have spent 11 days in space change significantly. Specifically, about 8% more fibers express fast MHCs and all phenotypes atrophy in the vastus lateralis (VL) post compared to preflight. In the present paper we examine the relationships among the population of myonuclei, MHC type, and CSA of single human muscle fibers before and after spaceflight. These are the first data that define the relationship among the types of MHC expressed, myonuclei number, and myonuclei domain of single fibers in human muscle. We then compare these data to similar measures in the cat. In addition, the maximal torque that can be generated by the knee extensors and their fatigability before and after spaceflight are examined. These data provide some indication of the potential physiologica consequences of the muscle adaptations that occur in humans in response to spaceflight.

  18. Thixotropy and Rheopexy of Muscle Fibers Probed Using Sinusoidal Oscillations

    PubMed Central

    Altman, David; Minozzo, Fabio C.; Rassier, Dilson E.

    2015-01-01

    Length changes of muscle fibers have previously been shown to result in a temporary reduction in fiber stiffness that is referred to as thixotropy. Understanding the mechanism of this thixotropy is important to our understanding of muscle function since there are many instances in which muscle is subjected to repeated patterns of lengthening and shortening. By applying sinusoidal length changes to one end of single permeabilized muscle fibers and measuring the force response at the opposite end, we studied the history-dependent stiffness of both relaxed and activated muscle fibers. For length change oscillations greater than 1 Hz, we observed thixotropic behavior of activated fibers. Treatment of these fibers with EDTA and blebbistatin, which inhibits myosin-actin interactions, quashed this effect, suggesting that the mechanism of muscle fiber thixotropy is cross-bridge dependent. We modeled a half-sarcomere experiencing sinusoidal length changes, and our simulations suggest that thixotropy could arise from force-dependent cross-bridge kinetics. Surprisingly, we also observed that, for length change oscillations less than 1 Hz, the muscle fiber exhibited rheopexy. In other words, the stiffness of the fiber increased in response to the length changes. Blebbistatin and EDTA did not disrupt the rheopectic behavior, suggesting that a non-cross-bridge mechanism contributes to this phenomenon. PMID:25880774

  19. Composition of Muscle Fiber Types in Rat Rotator Cuff Muscles.

    PubMed

    Rui, Yongjun; Pan, Feng; Mi, Jingyi

    2016-10-01

    The rat is a suitable model to study human rotator cuff pathology owing to the similarities in morphological anatomy structure. However, few studies have reported the composition muscle fiber types of rotator cuff muscles in the rat. In this study, the myosin heavy chain (MyHC) isoforms were stained by immunofluorescence to show the muscle fiber types composition and distribution in rotator cuff muscles of the rat. It was found that rotator cuff muscles in the rat were of mixed fiber type composition. The majority of rotator cuff fibers labeled positively for MyHCII. Moreover, the rat rotator cuff muscles contained hybrid fibers. So, compared with human rotator cuff muscles composed partly of slow-twitch fibers, the majority of fast-twitch fibers in rat rotator cuff muscles should be considered when the rat model study focus on the pathological process of rotator cuff muscles after injury. Gaining greater insight into muscle fiber types in rotator cuff muscles of the rat may contribute to elucidate the mechanism of pathological change in rotator cuff muscles-related diseases. Anat Rec, 299:1397-1401, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Preferential type II muscle fiber damage from plyometric exercise.

    PubMed

    Macaluso, Filippo; Isaacs, Ashwin W; Myburgh, Kathryn H

    2012-01-01

    Plyometric training has been successfully used in different sporting contexts. Studies that investigated the effect of plyometric training on muscle morphology are limited, and results are controversial with regard to which muscle fiber type is mainly affected. To analyze the skeletal muscle structural and ultrastructural change induced by an acute bout of plyometric exercise to determine which type of muscle fibers is predominantly damaged. Descriptive laboratory study. Research laboratory. Eight healthy, untrained individuals (age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg). Participants completed an acute bout of plyometric exercise (10 sets of 10 squat-jumps with a 1-minute rest between sets). Blood samples were collected 9 days and immediately before and 6 hours and 1, 2, and 3 days after the acute intervention. Muscle samples were collected 9 days before and 3 days after the exercise intervention. Blood samples were analyzed for creatine kinase activity. Muscle biopsies were analyzed for damage using fluorescent and electron transmission microscopy. Creatine kinase activity peaked 1 day after the exercise bout (529.0 ± 317.8 U/L). Immunofluorescence revealed sarcolemmal damage in 155 of 1616 fibers analyzed. Mainly fast-twitch fibers were damaged. Within subgroups, 7.6% of type I fibers, 10.3% of type IIa fibers, and 14.3% of type IIx fibers were damaged as assessed by losses in dystrophin staining. Similar damage was prevalent in IIx and IIa fibers. Electron microscopy revealed clearly distinguishable moderate and severe sarcomere damage, with damage quantifiably predominant in type II muscle fibers of both the glycolytic and oxidative subtypes (86% and 84%, respectively, versus only 27% of slow-twitch fibers). We provide direct evidence that a single bout of plyometric exercise affected mainly type II muscle fibers.

  1. Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers

    NASA Technical Reports Server (NTRS)

    Tseng, B. S.; Kasper, C. E.; Edgerton, V. R.

    1994-01-01

    The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n = 54; 9 +/- 3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabeled with fast and slow myosin heavy chain monoclonal antibodies. Mean +/- S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112 +/- 69 vs. 34 +/- 21 x 10(3) microns3) than fast and slow soleus fibers (40 +/- 20 vs. 30 +/- 14 x 10(3) microns3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (< 70 microns) fast soleus and plantaris fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (> 70 microns) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116 +/- 51 vs. 55 +/- 22 and 44 +/- 23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability.

  2. The muscle fiber type–fiber size paradox: hypertrophy or oxidative metabolism?

    PubMed Central

    van Wessel, T.; de Haan, A.; van der Laarse, W. J.

    2010-01-01

    An inverse relationship exists between striated muscle fiber size and its oxidative capacity. This relationship implies that muscle fibers, which are triggered to simultaneously increase their mass/strength (hypertrophy) and fatigue resistance (oxidative capacity), increase these properties (strength or fatigue resistance) to a lesser extent compared to fibers increasing either of these alone. Muscle fiber size and oxidative capacity are determined by the balance between myofibrillar protein synthesis, mitochondrial biosynthesis and degradation. New experimental data and an inventory of critical stimuli and state of activation of the signaling pathways involved in regulating contractile and metabolic protein turnover reveal: (1) higher capacity for protein synthesis in high compared to low oxidative fibers; (2) competition between signaling pathways for synthesis of myofibrillar proteins and proteins associated with oxidative metabolism; i.e., increased mitochondrial biogenesis via AMP-activated protein kinase attenuates the rate of protein synthesis; (3) relatively higher expression levels of E3-ligases and proteasome-mediated protein degradation in high oxidative fibers. These observations could explain the fiber type–fiber size paradox that despite the high capacity for protein synthesis in high oxidative fibers, these fibers remain relatively small. However, it remains challenging to understand the mechanisms by which contractile activity, mechanical loading, cellular energy status and cellular oxygen tension affect regulation of fiber size. Therefore, one needs to know the relative contribution of the signaling pathways to protein turnover in high and low oxidative fibers. The outcome and ideas presented are relevant to optimizing treatment and training in the fields of sports, cardiology, oncology, pulmonology and rehabilitation medicine. Electronic supplementary material The online version of this article (doi:10.1007/s00421-010-1545-0) contains

  3. From single muscle fiber to whole muscle mechanics: a finite element model of a muscle bundle with fast and slow fibers.

    PubMed

    Marcucci, Lorenzo; Reggiani, Carlo; Natali, Arturo N; Pavan, Piero G

    2017-12-01

    Muscles exhibit highly complex, multi-scale architecture with thousands of muscle fibers, each with different properties, interacting with each other and surrounding connective structures. Consequently, the results of single-fiber experiments are scarcely linked to the macroscopic or whole muscle behavior. This is especially true for human muscles where it would be important to understand of how skeletal muscles disorders affect patients' life. In this work, we developed a mathematical model to study how fast and slow muscle fibers, well characterized in single-fiber experiments, work and generate together force and displacement in muscle bundles. We characterized the parameters of a Hill-type model, using experimental data on fast and slow single human muscle fibers, and comparing experimental data with numerical simulations obtained from finite element (FE) models of single fibers. Then, we developed a FE model of a bundle of 19 fibers, based on an immunohistochemically stained cross section of human diaphragm and including the corresponding properties of each slow or fast fiber. Simulations of isotonic contractions of the bundle model allowed the generation of its apparent force-velocity relationship. Although close to the average of the force-velocity curves of fast and slow fibers, the bundle curve deviates substantially toward the fast fibers at low loads. We believe that the present model and the characterization of the force-velocity curve of a fiber bundle represents the starting point to link the single-fiber properties to those of whole muscle with FE application in phenomenological models of human muscles.

  4. Fiber typing in aging muscle.

    PubMed

    Purves-Smith, Fennigje M; Sgarioto, Nicolas; Hepple, Russell T

    2014-04-01

    It is accepted widely that fast-twitch muscle fibers are preferentially impacted in aging muscle, yet we hypothesize that this is not valid when aging muscle atrophy becomes severe. In this review, we summarize the evidence of fiber type-specific effect in aging muscle and the potential confounding roles of fibers coexpressing multiple myosin heavy-chain isoforms and their histochemical identification.

  5. Skeletal muscle fiber, nerve, and blood vessel breakdown in space-flown rats

    NASA Technical Reports Server (NTRS)

    Riley, D. A.; Ilyina-Kakueva, E. I.; Ellis, S.; Bain, J. L.; Slocum, G. R.; Sedlak, F. R.

    1990-01-01

    Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non-weight-bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule-rich mast cells were diminished in flight AL muscles compared with controls, indicating the mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation.

  6. Chronic low-frequency stimulation transforms cat masticatory muscle fibers into jaw-slow fibers.

    PubMed

    Kang, Lucia H D; Hoh, Joseph F Y

    2011-09-01

    Cat masticatory muscle during regeneration expresses masticatory-specific myofibrillar proteins upon innervation by a fast muscle nerve but acquires the jaw-slow phenotype when innervated by a slow muscle nerve. Here, we test the hypothesis that chronic low-frequency stimulation simulating impulses from the slow nerve can result in masticatory-to-slow fiber-type transformation. In six cats, the temporalis muscle was continuously stimulated directly at 10 Hz for up to 12 weeks using a stimulator affixed to the skull. Stimulated muscles were analyzed by immunohistochemistry using, among others, monoclonal antibodies against masticatory-specific myosin heavy chain (MyHC), myosin binding protein-C, and tropomyosins. Under the electrodes, stimulation induced muscle regeneration, which generated slow fibers. Deep to the electrodes, at two to three weeks, two distinct populations of masticatory fibers began to express slow MyHC: 1) evenly distributed fibers that completely suppressed masticatory-specific proteins but transiently co-expressed fetal MyHCs, and 2) incompletely transformed fibers that express slow and masticatory but not fetal MyHCs. SDS-PAGE confirmed de novo expression of slow MyHC and β-tropomyosin in the stimulated muscles. We conclude that chronic low-frequency stimulation induces masticatory-to-slow fiber-type conversion. The two populations of transforming masticatory fibers may differ in their mode of activation or lineage of their myogenic cells.

  7. Human Muscle Fiber

    NASA Technical Reports Server (NTRS)

    2003-01-01

    The stimulus of gravity affects RNA production, which helps maintain the strength of human muscles on Earth (top), as seen in this section of muscle fiber taken from an astronaut before spaceflight. Astronauts in orbit and patients on Earth fighting muscle-wasting diseases need countermeasures to prevent muscle atrophy, indicated here with white lipid droplets (bottom) in the muscle sample taken from the same astronaut after spaceflight. Kerneth Baldwin of the University of California, Irvine, is conducting research on how reducing the stimulus of gravity affects production of the RNA that the body uses as a blueprint for making muscle proteins. Muscle proteins are what give muscles their strength, so when the RNA blueprints aren't available for producing new proteins to replace old ones -- a situation that occurs in microgravity -- the muscles atrophy. When the skeletal muscle system is exposed to microgravity during spaceflight, the muscles undergo a reduced mass that translates to a reduction in strength. When this happens, muscle endurance decreases and the muscles are more prone to injury, so individuals could have problems in performing extravehicular activity [space walks] or emergency egress because their bodies are functionally compromised.

  8. Preferential Type II Muscle Fiber Damage From Plyometric Exercise

    PubMed Central

    Macaluso, Filippo; Isaacs, Ashwin W.; Myburgh, Kathryn H.

    2012-01-01

    Context Plyometric training has been successfully used in different sporting contexts. Studies that investigated the effect of plyometric training on muscle morphology are limited, and results are controversial with regard to which muscle fiber type is mainly affected. Objective To analyze the skeletal muscle structural and ultrastructural change induced by an acute bout of plyometric exercise to determine which type of muscle fibers is predominantly damaged. Design Descriptive laboratory study. Setting Research laboratory. Patients or Other Participants Eight healthy, untrained individuals (age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg). Intervention(s) Participants completed an acute bout of plyometric exercise (10 sets of 10 squat-jumps with a 1-minute rest between sets). Main Outcome Measure(s) Blood samples were collected 9 days and immediately before and 6 hours and 1, 2, and 3 days after the acute intervention. Muscle samples were collected 9 days before and 3 days after the exercise intervention. Blood samples were analyzed for creatine kinase activity. Muscle biopsies were analyzed for damage using fluorescent and electron transmission microscopy. Results Creatine kinase activity peaked 1 day after the exercise bout (529.0 ± 317.8 U/L). Immunofluorescence revealed sarcolemmal damage in 155 of 1616 fibers analyzed. Mainly fast-twitch fibers were damaged. Within subgroups, 7.6% of type I fibers, 10.3% of type IIa fibers, and 14.3% of type IIx fibers were damaged as assessed by losses in dystrophin staining. Similar damage was prevalent in IIx and IIa fibers. Electron microscopy revealed clearly distinguishable moderate and severe sarcomere damage, with damage quantifiably predominant in type II muscle fibers of both the glycolytic and oxidative subtypes (86% and 84%, respectively, versus only 27% of slow-twitch fibers). Conclusions We provide direct evidence that a single bout of plyometric exercise affected mainly type II muscle

  9. Muscle fiber type specific induction of slow myosin heavy chain 2 gene expression by electrical stimulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Crew, Jennifer R.; Falzari, Kanakeshwari; DiMario, Joseph X., E-mail: joseph.dimario@rosalindfranklin.edu

    Vertebrate skeletal muscle fiber types are defined by a broad array of differentially expressed contractile and metabolic protein genes. The mechanisms that establish and maintain these different fiber types vary throughout development and with changing functional demand. Chicken skeletal muscle fibers can be generally categorized as fast and fast/slow based on expression of the slow myosin heavy chain 2 (MyHC2) gene in fast/slow muscle fibers. To investigate the cellular and molecular mechanisms that control fiber type formation in secondary or fetal muscle fibers, myoblasts from the fast pectoralis major (PM) and fast/slow medial adductor (MA) muscles were isolated, allowed tomore » differentiate in vitro, and electrically stimulated. MA muscle fibers were induced to express the slow MyHC2 gene by electrical stimulation, whereas PM muscle fibers did not express the slow MyHC2 gene under identical stimulation conditions. However, PM muscle fibers did express the slow MyHC2 gene when electrical stimulation was combined with inhibition of inositol triphosphate receptor (IP3R) activity. Electrical stimulation was sufficient to increase nuclear localization of expressed nuclear-factor-of-activated-T-cells (NFAT), NFAT-mediated transcription, and slow MyHC2 promoter activity in MA muscle fibers. In contrast, both electrical stimulation and inhibitors of IP3R activity were required for these effects in PM muscle fibers. Electrical stimulation also increased levels of peroxisome-proliferator-activated receptor-{gamma} co-activator-1 (PGC-1{alpha}) protein in PM and MA muscle fibers. These results indicate that MA muscle fibers can be induced by electrical stimulation to express the slow MyHC2 gene and that fast PM muscle fibers are refractory to stimulation-induced slow MyHC2 gene expression due to fast PM muscle fiber specific cellular mechanisms involving IP3R activity.« less

  10. Distinct muscle apoptotic pathways are activated in muscles with different fiber types in a rat model of critical illness myopathy.

    PubMed

    Barnes, Benjamin T; Confides, Amy L; Rich, Mark M; Dupont-Versteegden, Esther E

    2015-06-01

    Critical illness myopathy (CIM) is associated with severe muscle atrophy and fatigue in affected patients. Apoptotic signaling is involved in atrophy and is elevated in muscles from patients with CIM. In this study we investigated underlying mechanisms of apoptosis-related pathways in muscles with different fiber type composition in a rat model of CIM using denervation and glucocorticoid administration (denervation and steroid-induced myopathy, DSIM). Soleus and tibialis anterior (TA) muscles showed severe muscle atrophy (40-60% of control muscle weight) and significant apoptosis in interstitial as well as myofiber nuclei that was similar between the two muscles with DSIM. Caspase-3 and -8 activities, but not caspase-9 and -12, were elevated in TA and not in soleus muscle, while the caspase-independent proteins endonuclease G (EndoG) and apoptosis inducing factor (AIF) were not changed in abundance nor differentially localized in either muscle. Anti-apoptotic proteins HSP70, -27, and apoptosis repressor with a caspase recruitment domain (ARC) were elevated in soleus compared to TA muscle and ARC was significantly decreased with induction of DSIM in soleus. Results indicate that apoptosis is a significant process associated with DSIM in both soleus and TA muscles, and that apoptosis-associated processes are differentially regulated in muscles of different function and fiber type undergoing atrophy due to DSIM. We conclude that interventions combating apoptosis with CIM may need to be directed towards inhibiting caspase-dependent as well as -independent mechanisms to be able to affect muscles of all fiber types.

  11. A study of the effect of pregnancy on muscle fibers of the rectus abdominis muscle of the rat.

    PubMed

    Martin, W D

    1979-11-01

    Samples of the rectus abdominis muscle were taken from Sprague-Dawley rats at 0, 3, 6, 6, 12, 15, 18, and 21 days of pregnancy, and at 1, 3, 6, 9, 12, and 15 days of postpartum. Sections were incubated for actomyosin adenosine triphosphatase activity following preincubation at a basic pH. Muscle fibers within a unit area of each sample were identified as to fiber type according to their enzyme activity, and the population of each type counted. The proportion of each fiber type was calculated and the diameter of 24 fibers of each type measured. No changes were noted in the muscle fiber proportions through the course of the experiment. Differential changes in muscle fiber diameters were noted in each of the three muscle fiber types. Slow oxidative fibers underwent an increase in diameter through the last half of pregnancy. The diameter was further increased as stretch of the muscle was released after birth, and did not decrease in the postpartum period. Fast glycolytic fibers decreased in diameter during the last half of pregnancy, but returned to the prepregnancy diameter in the first postpartum day. The diameter of the fast oxidative glycolytic fibers remained unchanged through the course of pregnacy and in the postpartum period.

  12. Reduced fiber size, capillary supply and mitochondrial activity in constitutional thinness' skeletal muscle.

    PubMed

    Galusca, Bogdan; Verney, Julien; Meugnier, Emmanuelle; Ling, Yiin; Edouard, Pascal; Feasson, Leonard; Ravelojaona, Marion; Vidal, Hubert; Estour, Bruno; Germain, Natacha

    2018-05-13

    Constitutional thinness (CT) is a rare condition of natural low bodyweight, with no psychological issues, no marker of undernutrition and a resistance to weight gain. This study evaluated the skeletal muscle phenotype of CT women by comparison to a normal BMI control group. 10 CT women (BMI< 17.5 kg/m2) and 10 female controls (BMI: 18.5-25 kg/m2) underwent metabolic and hormonal assessment along with muscle biopsies to analyse the skeletal muscular fibers pattern, capillarity, enzymes activities and transcriptomics. CTs displayed similar energy balance metabolic and hormonal profile to controls. CTs presented with lower mean area of all the skeletal muscular fibers (-24%, p= 0.01) and percentage of slow-twitch type I fibers (-25%, p=0.02, respectively). Significant down regulation of the mRNA expression of several mitochondrial related genes and triglycerides metabolism was found along with low Cytochrome C Oxydase (COX) activity and capillary network in type I fibers. Pre and post mitochondrial respiratory chain enzymes levels were found similar to controls. Transcriptomics also revealed downregulation of cytoskeletal related genes. Diminished type I fibers, decreased mitochondrial and metabolic activity suggested by these results are discordant with normal resting metabolic rate of CT subjects. Downregulated genes related to cytoskeletal proteins and myocyte differentiation could account for CT's resistance to weight gain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Measurement of Maximum Isometric Force Generated by Permeabilized Skeletal Muscle Fibers.

    PubMed

    Roche, Stuart M; Gumucio, Jonathan P; Brooks, Susan V; Mendias, Christopher L; Claflin, Dennis R

    2015-06-16

    Analysis of the contractile properties of chemically skinned, or permeabilized, skeletal muscle fibers offers a powerful means by which to assess muscle function at the level of the single muscle cell. Single muscle fiber studies are useful in both basic science and clinical studies. For basic studies, single muscle fiber contractility measurements allow investigation of fundamental mechanisms of force production, and analysis of muscle function in the context of genetic manipulations. Clinically, single muscle fiber studies provide useful insight into the impact of injury and disease on muscle function, and may be used to guide the understanding of muscular pathologies. In this video article we outline the steps required to prepare and isolate an individual skeletal muscle fiber segment, attach it to force-measuring apparatus, activate it to produce maximum isometric force, and estimate its cross-sectional area for the purpose of normalizing the force produced.

  14. The Regulation of Skeletal Muscle Active Hyperemia: The Differential Role of Adenosine in Muscles of Varied Fiber Types

    DTIC Science & Technology

    1986-04-21

    Role of Adenosine in Muscles of Varied Fiber Types 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...Role of Adenosine in Muscles of Varied Fiber Types Name of Candidate: Lisa M. Schwartz Doctor of Philosophy Degree Ap r i 1 21 , 1 9 8 6 Thesis and...adenosine in muscles of varied fiber types Lisa M. Schwartz, Doctor of Philosophy, 1986 Dissertation Directed by: Jack E. McKenzie, Associate

  15. Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen

    PubMed Central

    Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

    2016-01-01

    Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active

  16. Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen.

    PubMed

    Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

    2016-09-15

    Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active

  17. An evaluation of the reliability of muscle fiber cross-sectional area and fiber number measurements in rat skeletal muscle

    USDA-ARS?s Scientific Manuscript database

    Background: The reliability of estimating muscle fiber cross-sectional area (measure of muscle fiber size) and fiber number from only a subset of fibers in rat hindlimb muscle cross-sections has not been systematically evaluated. This study examined the variability in mean estimates of fiber cross-s...

  18. Intermuscular relationship of human muscle fiber type proportions: slow leg muscles predict slow neck muscles.

    PubMed

    Vikne, Harald; Gundersen, Kristian; Liestøl, Knut; Maelen, Jan; Vøllestad, Nina

    2012-04-01

    Our aim in this study was to examine whether the muscle fiber type proportions in different muscles from the same individual are interrelated. Samples were excised from five skeletal muscles in each of 12 human autopsy cases, and the fiber type proportions were determined by immunohistochemistry. We further examined the intermuscular relationship in fiber type proportion by reanalyzing three previously published data sets involving other muscles. Subjects demonstrated a predominantly high or low proportion of type 1 fibers in all examined muscles, and the overall difference between individuals was statistically significant (P < 0.001). Accordingly, the type 1 fiber proportions in most muscles were positively correlated (median r = 0.42, range -0.03-0.80). Similar results were also obtained from the three reanalyzed data sets. We suggest the existence of an across-muscle phenotype with respect to fiber type proportions; some individuals display generally faster muscles and some individuals slower muscles when compared with others. Copyright © 2011 Wiley Periodicals, Inc.

  19. Mechanical properties and fiber type composition of chronically inactive muscles

    NASA Technical Reports Server (NTRS)

    Roy, R. R.; Zhong, H.; Monti, R. J.; Vallance, K. A.; Kim, J. A.; Edgerton, V. R.

    2000-01-01

    A role for neuromuscular activity in the maintenance of skeletal muscle properties has been well established. However, the role of activity-independent factors is more difficult to evaluate. We have used the spinal cord isolation model to study the effects of chronic inactivity on the mechanical properties of the hindlimb musculature in cats and rats. This model maintains the connectivity between the motoneurons and the muscle fibers they innervate, but the muscle unit is electrically "silent". Consequently, the measured muscle properties are activity-independent and thus the advantage of using this model is that it provides a baseline level (zero activity) from which regulatory factors that affect muscle cell homeostasis can be defined. In the present paper, we will present a brief review of our findings using the spinal cord isolation model related to muscle mechanical and fiber type properties.

  20. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure.

    PubMed

    Delp, M D; Duan, C; Mattson, J P; Musch, T I

    1997-10-01

    One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls (n = 13) and rats with moderate (n = 10) and severe (n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations (P < 0.05) in left ventricular end-diastolic pressure (sham, 5 +/- 1 mmHg; moderate LVD, 11 +/- 1 mmHg; severe LVD, 25 +/- 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and beta-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

  1. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

    NASA Technical Reports Server (NTRS)

    Delp, M. D.; Duan, C.; Mattson, J. P.; Musch, T. I.

    1997-01-01

    One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls (n = 13) and rats with moderate (n = 10) and severe (n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations (P < 0.05) in left ventricular end-diastolic pressure (sham, 5 +/- 1 mmHg; moderate LVD, 11 +/- 1 mmHg; severe LVD, 25 +/- 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and beta-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

  2. Effects of divergent selection for 8-week body weight on postnatal enzyme activity pattern of 3 fiber types in fast muscles of male broilers (Gallus gallus domesticus).

    PubMed

    Dahmane Gosnak, R; Erzen, I; Holcman, A; Skorjanc, D

    2010-12-01

    A divergent selection experiment was conducted for 8-wk BW in chickens. At 3, 6, 9, and 12 wk of age, samples of pectoralis profundus (PP) and biceps femoris (BF) muscles from fast-growing and slow-growing lines were used to estimate the enzyme activities and muscle fiber diameter. Microphotometric measurements made in situ of succinate dehydrogenase (SDH, EC 1.3.99.1) and glycerol-3-phosphate dehydrogenase (GPDH, EC 1.1.99.5) were completed on serial sections of PP and BF muscles from male chickens, in order to examine the ratio of SDH:GPDH activity in single fibers. On the basis of the SDH:GPDH activity ratios, muscle fibers were divided using cluster analysis into 3 populations of different fiber types (O = oxidative, OG = oxidative-glycolytic, and G = glycolytic). Cockerels of the SGL attained an 8.1-fold increase and those of the FGL a 6.8-fold increase in BW at 12 wk compared with that at 3 wk of age. The O, OG, and G type fibers of the BF muscles of the SGL had significantly (P ≤ 0.001) lower SDH:GPDH activity ratios than those of the FGL. A step decrease in the SDH:GPDH activity of O, OG, and G fibers in the PP of both lines occurred, and this differed significantly between SGL and FGL (P ≤ 0.001). Age and line effects influenced the diameter of the 3 fiber types in the BF muscle only. In contrast to this response, all 3 fiber types of the PP muscles reached similar diameters in both lines during the growth process from wk 3 to 12. From the results of this study, we concluded that the activities of metabolic enzymes in skeletal muscle fibers are under the influence of muscle type, age, and selection pressure. Microphotometry is a suitable method for the evaluation of enzyme activity measured in a single muscle fiber. The method enables precise estimation of enzyme activities, especially in muscles composed of populations of different metabolic fiber types.

  3. Mechanisms of nascent fiber formation during avian skeletal muscle hypertrophy

    NASA Technical Reports Server (NTRS)

    McCormick, K. M.; Schultz, E.

    1992-01-01

    This study examined two putative mechanisms of new fiber formation in postnatal skeletal muscle, namely longitudinal fragmentation of existing fibers and de novo formation. The relative contributions of these two mechanisms to fiber formation in hypertrophying anterior latissimus dorsi (ALD) muscle were assessed by quantitative analysis of their nuclear populations. Muscle hypertrophy was induced by wing-weighting for 1 week. All nuclei formed during the weighting period were labeled by continuous infusion of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analog, and embryonic-like fibers were identified using an antibody to ventricular-like embryonic (V-EMB) myosin. The number of BrdU-labeled and unlabeled nuclei in V-EMB-positive fibers were counted. Wing-weighting resulted in significant muscle enlargement and the appearance of many V-EMB+ fibers. The majority of V-EMB+ fibers were completely independent of mature fibers and had a nuclear density characteristics of developing fibers. Furthermore, nearly 100% of the nuclei in independent V-EMB+ fibers were labeled. These findings strongly suggest that most V-EMB+ fibers were nascent fibers formed de novo during the weighting period by satellite cell activation and fusion. Nascent fibers were found primarily in the space between fascicles where they formed a complex anastomosing network of fibers running at angles to one another. Although wing-weighting induced an increase in the number of branched fibers, there was no evidence that V-EMB+ fibers were formed by longitudinal fragmentation. The location of newly formed fibers in wing-weighted and regenerating ALD muscle was compared to determine whether satellite cells in the ALD muscle were unusual in that, if stimulated to divide, they would form fibers in the inter- and intrafascicular space. In contrast to wing-weighted muscle, nascent fibers were always found closely associated with necrotic fibers. These results suggest that wing-weighting is not simply another

  4. Fiber-type differences in muscle mitochondrial profiles.

    PubMed

    Leary, S C; Lyons, C N; Rosenberger, A G; Ballantyne, J S; Stillman, J; Moyes, C D

    2003-10-01

    Although striated muscles differ in mitochondrial content, the extent of fiber-type specific mitochondrial specializations is not well known. To address this issue, we compared mitochondrial structural and functional properties in red muscle (RM), white muscle (WM), and cardiac muscle of rainbow trout. Overall preservation of the basic relationships between oxidative phosphorylation complexes among fiber types was confirmed by kinetic analyses, immunoblotting of native holoproteins, and spectroscopic measurements of cytochrome content. Fiber-type differences in mitochondrial properties were apparent when parameters were expressed per milligram mitochondrial protein. However, the differences diminished when expressed relative to cytochrome oxidase (COX), possibly a more meaningful denominator than mitochondrial protein. Expressed relative to COX, there were no differences in oxidative phosphorylation enzyme activities, pyruvate-based respiratory rates, H2O2 production, or state 4 proton leak respiration. These data suggest most mitochondrial qualitative properties are conserved across fiber types. However, there remained modest differences ( approximately 50%) in stoichiometries of selected enzymes of the Krebs cycle, beta-oxidation, and antioxidant enzymes. There were clear differences in membrane fluidity (RM > cardiac, WM) and proton conductance (H+/min/mV/U COX: WM > RM > cardiac). The pronounced differences in mitochondrial content between fiber types could be attributed to a combination of differences in myonuclear domain and modest effects on the expression of nuclear- and mitochondrially encoded respiratory genes. Collectively, these studies suggest constitutive pathways that transcend fiber types are primarily responsible for determining most quantitative and qualitative properties of mitochondria.

  5. Beef extract supplementation increases leg muscle mass and modifies skeletal muscle fiber types in rats.

    PubMed

    Yoshihara, Hiroyuki; Wakamatsu, Jun-Ichiro; Kawabata, Fuminori; Mori, Sunao; Haruno, Atsushi; Hayashi, Toshiya; Sekiguchi, Takeshi; Mizunoya, Wataru; Tatsumi, Ryuichi; Ito, Tatsumi; Ikeuchi, Yoshihide

    2006-06-01

    The objective of this research was to investigate the effects of beef extract on fat metabolism, muscle mass and muscle fiber types in rats. We also investigated the synergetic effect of endurance exercise. Twenty-four male rats weighing about 270 g were assigned to two diets containing 0 or 6% beef extract (BE). Half the rats fed each diet were subjected to compulsory exercise (CE) for 30 min every other day. After 4 weeks feeding, the blood was collected and various organs were dissected. The muscle fiber type of the soleus and extensor digitorum longus (EDL) muscles were evaluated by histochemical and electrophoretical analyses. Rats supplemented with BE showed a decrease in fat content in liver and abdomen and an increase in the activity of carnitine palmitoyl transferase II in liver. BE as well as exercise increased the relative weights of both soleus and EDL. BE alone and BE plus CE did not affect the distribution of muscle fiber types in soleus. BE without exercise decreased in type IIb of EDL from 54% to 44% with compensatory increase in type IIa from 41% to 49% and type I from 5% to 7% compared with the nonsupplemented, nonexercised control group. No synergetic effect on a fast to slow fiber conversion due to the combination of BE and CE was detected. Thus, BE supplement increased muscle mass and slow type fiber in EDL. The effects of BE supplement on muscle characteristics were similar to those of exercise. beef extract, fat metabolism, muscle fiber type, muscle mass, L-carnitine

  6. Selective recruitment of the lower fibers of the trapezius muscle.

    PubMed

    Arlotta, Melissa; Lovasco, Gina; McLean, Linda

    2011-06-01

    We aimed to determine the effectiveness of five isometric exercises at maximally activating the lower trapezius muscle in healthy subjects. Surface electromyography data were recorded from the upper, middle, and lower fibers of the trapezius muscle bilaterally while 18 healthy subjects performed five different exercises: Latissimus Pull-down, Prone Row, Prone V-Raise, Posterior Fly and Modified Prone Cobra. The peak activation was determined from the rectified and smoothed data to determine which exercise generated the highest amount of lower trapezius activity, and to determine which exercise best resulted in activation of the lower fibers of trapezius while minimizing activation of the upper and middle fibers of trapezius. Males and females demonstrated different patterns of lower trapezius recruitment and therefore the data were analyzed separately for each sex. For the males, the Prone Row exercise (2.84 ± 1.67 mV), the Posterior Fly (2.23 ± 1.00 mV) and the Modified Prone Cobra (2.26 ± 1.19 mV) exercises generated the highest EMG activity in the lower trapezius muscle. For the females, the Modified Prone Cobra (2.40 ± 1.32 mV) and the Prone Row (2.37 ± 1.14 mV) exercises generated higher activation than the Latissimus Pull Down (1.04 ± 0.56 mV), the Posterior Fly (1.62 ± 1.044 mV) and the Prone V-Raise (1.32 ± 1.07 mV). In both sexes, the Modified Prone Cobra, the Prone Row and the Latissimus Pull Down outperformed the other exercises in terms of maximizing lower trapezius activation while minimizing activation of the upper and middle fibers of trapezius. The Modified Prone Cobra showed lower relative activation of the upper trapezius muscle than did the Prone Row exercise. The Modified Prone Cobra and Prone Row exercises are the most effective exercises for targeted strengthening of the lower trapezius muscle in both sexes. The Modified Prone Cobra is somewhat better than the Prone Row due to the low activation of the upper trapezius muscle during

  7. ROS-mediated decline in maximum Ca2+-activated force in rat skeletal muscle fibers following in vitro and in vivo stimulation.

    PubMed

    Dutka, Travis L; Verburg, Esther; Larkins, Noni; Hortemo, Kristin H; Lunde, Per K; Sejersted, Ole M; Lamb, Graham D

    2012-01-01

    We hypothesised that normal skeletal muscle stimulated intensely either in vitro or in situ would exhibit reactive oxygen species (ROS)-mediated contractile apparatus changes common to many pathophysiological conditions. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat were bubbled with 95% O(2) and stimulated in vitro at 31°C to give isometric tetani (50 Hz for 0.5 s every 2 s) until maximum force declined to ≤30%. Skinned superficial slow-twitch fibers from the SOL muscles displayed a large reduction (∼41%) in maximum Ca(2+)-activated specific force (F(max)), with Ca(2+)-sensitivity unchanged. Fibers from EDL muscles were less affected. The decrease in F(max) in SOL fibers was evidently due to oxidation effects on cysteine residues because it was reversed if the reducing agent DTT was applied prior to activating the fiber. The GSH:GSSG ratio was ∼3-fold lower in the cytoplasm of superficial fibers from stimulated muscle compared to control, confirming increased oxidant levels. The presence of Tempol and L-NAME during in vitro stimulation prevented reduction in F(max). Skinned fibers from SOL muscles stimulated in vivo at 37°C with intact blood supply also displayed reduction in F(max), though to a much smaller extent (∼12%). Thus, fibers from muscles stimulated even with putatively adequate O(2) supply display a reversible oxidation-induced decrease in F(max) without change in Ca(2+)-sensitivity, consistent with action of peroxynitrite (or possibly superoxide) on cysteine residues of the contractile apparatus. Significantly, the changes closely resemble the contractile deficits observed in a range of pathophysiological conditions. These findings highlight how readily muscle experiences ROS-related deficits, and also point to potential difficulties when defining muscle performance and fatigue.

  8. ROS-Mediated Decline in Maximum Ca2+-Activated Force in Rat Skeletal Muscle Fibers following In Vitro and In Vivo Stimulation

    PubMed Central

    Dutka, Travis L.; Verburg, Esther; Larkins, Noni; Hortemo, Kristin H.; Lunde, Per K.; Sejersted, Ole M.; Lamb, Graham D.

    2012-01-01

    We hypothesised that normal skeletal muscle stimulated intensely either in vitro or in situ would exhibit reactive oxygen species (ROS)-mediated contractile apparatus changes common to many pathophysiological conditions. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat were bubbled with 95% O2 and stimulated in vitro at 31°C to give isometric tetani (50 Hz for 0.5 s every 2 s) until maximum force declined to ≤30%. Skinned superficial slow-twitch fibers from the SOL muscles displayed a large reduction (∼41%) in maximum Ca2+-activated specific force (Fmax), with Ca2+-sensitivity unchanged. Fibers from EDL muscles were less affected. The decrease in Fmax in SOL fibers was evidently due to oxidation effects on cysteine residues because it was reversed if the reducing agent DTT was applied prior to activating the fiber. The GSH∶GSSG ratio was ∼3-fold lower in the cytoplasm of superficial fibers from stimulated muscle compared to control, confirming increased oxidant levels. The presence of Tempol and L-NAME during in vitro stimulation prevented reduction in Fmax. Skinned fibers from SOL muscles stimulated in vivo at 37°C with intact blood supply also displayed reduction in Fmax, though to a much smaller extent (∼12%). Thus, fibers from muscles stimulated even with putatively adequate O2 supply display a reversible oxidation-induced decrease in Fmax without change in Ca2+-sensitivity, consistent with action of peroxynitrite (or possibly superoxide) on cysteine residues of the contractile apparatus. Significantly, the changes closely resemble the contractile deficits observed in a range of pathophysiological conditions. These findings highlight how readily muscle experiences ROS-related deficits, and also point to potential difficulties when defining muscle performance and fatigue. PMID:22629297

  9. Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension

    PubMed Central

    Manders, Emmy; Bonta, Peter I.; Kloek, Jaap J.; Symersky, Petr; Bogaard, Harm-Jan; Hooijman, Pleuni E.; Jasper, Jeff R.; Malik, Fady I.; Stienen, Ger J. M.; Vonk-Noordegraaf, Anton; de Man, Frances S.

    2016-01-01

    Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients (N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls (N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast-twitch muscle fibers of CTEPH patients, resulting in a ∼40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 μM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients. PMID:27190061

  10. Restricting calcium currents is required for correct fiber type specification in skeletal muscle

    PubMed Central

    Sultana, Nasreen; Dienes, Beatrix; Benedetti, Ariane; Tuluc, Petronel; Szentesi, Peter; Sztretye, Monika; Rainer, Johannes; Hess, Michael W.; Schwarzer, Christoph; Obermair, Gerald J.; Csernoch, Laszlo

    2016-01-01

    ABSTRACT Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel CaV1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental CaV1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted CaV1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental CaV1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease. PMID:26965373

  11. Gravitational unloading effects on muscle fiber size, phenotype and myonuclear number

    NASA Technical Reports Server (NTRS)

    Ohira, Y.; Yoshinaga, T.; Nomura, T.; Kawano, F.; Ishihara, A.; Nonaka, I.; Roy, R. R.; Edgerton, V. R.

    2002-01-01

    The effects of gravitational unloading with or without intact neural activity and/or tension development on myosin heavy chain (MHC) composition, cross-sectional area (CSA), number of myonuclei, and myonuclear domain (cytoplasmic volume per myonucleus ratio) in single fibers of both slow and fast muscles of rat hindlimbs are reviewed briefly. The atrophic response to unloading is generally graded as follows: slow extensors > fast extensors > fast flexors. Reduction of CSA is usually greater in the most predominant fiber type of that muscle. The percentage of fibers expressing fast MHC isoforms increases in unloaded slow but not fast muscles. Myonuclear number per mm of fiber length and myonuclear domain is decreased in the fibers of the unloaded predominantly slow soleus muscle, but not in the predominantly fast plantaris. Decreases in myonuclear number and domain, however, are observed in plantaris fibers when tenotomy, denervation, or both are combined with hindlimb unloading. All of these results are consistent with the view that a major factor for fiber atrophy is an inhibition or reduction of loading of the hindlimbs. These data also indicate that predominantly slow muscles are more responsive to unloading than predominantly fast muscles. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  12. Architecture and fiber type of the pyramidalis muscle.

    PubMed

    Lovering, Richard M; Anderson, Larry D

    2008-12-01

    The paired pyramidalis muscles are small triangular-shaped muscles that lie between the anterior surface of the rectus abdominus and the posterior surface of the rectus sheath. The precise function of pyramidalis muscles is unclear, but together the muscles are thought to tense the linea alba. The muscles are not always present, or are often unilateral, and vary greatly in size. Their wider inferior margins attach to the pubic symphyses and pubic crests, whereas their narrow superior margins attach to the linea alba. The gross anatomy and innervation of the pyramidalis muscles has been described by others, but their architecture and fiber type have not been determined in previous publications. The purpose of the present paper was therefore to investigate these parameters and place the findings into context for the literature available on this muscle. An example of bilateral pyramidalis muscles was recently encountered in a male cadaver that provided ample tissue for an analysis of its architecture and fiber type. The muscle mass, muscle length, fiber length, and pennation angle of muscle fibers were measured to ascertain physiological cross-sectional area and thereby estimate force production. Fiber type composition was also examined using immunofluorescent labeling. The results show that this is a muscle of mixed fiber type composition, similar to the rectus abdominus, and that the estimated forces generated by this muscle are relatively small.

  13. Poultry Meat Quality in Relation to Muscle Growth and Muscle Fiber Characteristics

    PubMed Central

    Ismail, Ishamri; Joo, Seon-Tea

    2017-01-01

    Variations in the definition of poultry meat quality exist because the quality traits are not solely based on intrinsic and extrinsic factors but also consumers’ preference. Appearance quality traits (AQT), eating quality traits (EQT), and reliance quality traits (RQT) are the major factors focused by the consumer before buying good quality of poultry meat. AQT and EQT of poultry meat are controlled by physical and biochemical characteristics of muscle fibers which can be categorized into a total number of fibers (TNF), cross-sectional area of fibers (CSAF), and fiber type composition (FTC). In poultry meat, it has been shown that muscle fiber properties play a key role in meat quality because numerous studies have reported the relationships between quality traits and fiber characteristics. Despite intensive research has been carried out to manipulate the muscle fiber to improve poultry meat quality, demand in a rapid growth of poultry muscle has correlated to the deterioration in the meat quality. The present paper reviews the definition of poultry meat quality, meat quality traits, and variations of meat quality. Also, this review presents recent knowledge underlying the relationship between poultry meat quality traits and muscle fiber characteristics. PMID:29725209

  14. How muscle fiber lengths and velocities affect muscle force generation as humans walk and run at different speeds

    PubMed Central

    Arnold, Edith M.; Hamner, Samuel R.; Seth, Ajay; Millard, Matthew; Delp, Scott L.

    2013-01-01

    SUMMARY The lengths and velocities of muscle fibers have a dramatic effect on muscle force generation. It is unknown, however, whether the lengths and velocities of lower limb muscle fibers substantially affect the ability of muscles to generate force during walking and running. We examined this issue by developing simulations of muscle–tendon dynamics to calculate the lengths and velocities of muscle fibers from electromyographic recordings of 11 lower limb muscles and kinematic measurements of the hip, knee and ankle made as five subjects walked at speeds of 1.0–1.75 m s−1 and ran at speeds of 2.0–5.0 m s−1. We analyzed the simulated fiber lengths, fiber velocities and forces to evaluate the influence of force–length and force–velocity properties on force generation at different walking and running speeds. The simulations revealed that force generation ability (i.e. the force generated per unit of activation) of eight of the 11 muscles was significantly affected by walking or running speed. Soleus force generation ability decreased with increasing walking speed, but the transition from walking to running increased the force generation ability by reducing fiber velocities. Our results demonstrate the influence of soleus muscle architecture on the walk-to-run transition and the effects of muscle–tendon compliance on the plantarflexors' ability to generate ankle moment and power. The study presents data that permit lower limb muscles to be studied in unprecedented detail by relating muscle fiber dynamics and force generation to the mechanical demands of walking and running. PMID:23470656

  15. Masticatory myosin unveiled: first determination of contractile parameters of muscle fibers from carnivore jaw muscles.

    PubMed

    Toniolo, Luana; Cancellara, Pasqua; Maccatrozzo, Lisa; Patruno, Marco; Mascarello, Francesco; Reggiani, Carlo

    2008-12-01

    Masticatory myosin heavy chain (M MyHC) is a myosin subunit isoform with expression restricted to muscles derived from the first branchial arch, such as jaw-closer muscles, with pronounced interspecies variability. Only sparse information is available on the contractile properties of muscle fibers expressing M MyHC (M fibers). In this study, we characterized M fibers isolated from the jaw-closer muscles (temporalis and masseter) of two species of domestic carnivores, the cat and the dog, compared with fibers expressing slow or fast (2A, 2X, and 2B) isoforms. In each fiber, during maximally calcium-activated contractions at 12 degrees C, we determined isometric-specific tension (P(o)), unloaded shortening velocity (v(o)) with the slack test protocol, and the rate constant of tension redevelopment (K(TR)) after a fast shortening-relengthening cycle. At the end of the mechanical experiment, we identified MyHC isoform composition of each fiber with gel electrophoresis. Electrophoretic migration rate of M MyHC was similar in both species. We found that in both species the kinetic parameters v(o) and K(TR) of M fibers were similar to those of 2A fibers, whereas P(o) values were significantly greater than in any other fiber types. The similarity between 2A and M fibers and the greater tension development of M fibers were confirmed also in mechanical experiments performed at 24 degrees C. Myosin concentration was determined in single fibers and found not different in M fibers compared with slow and fast fibers, suggesting that the higher tension developed by M fibers does not find an explanation in a greater number of force generators. The specific mechanical characteristics of M fibers might be attributed to a diversity in cross-bridge kinetics.

  16. Regionalizing muscle activity causes changes to the magnitude and direction of the force from whole muscles-a modeling study.

    PubMed

    Rahemi, Hadi; Nigam, Nilima; Wakeling, James M

    2014-01-01

    Skeletal muscle can contain neuromuscular compartments that are spatially distinct regions that can receive relatively independent levels of activation. This study tested how the magnitude and direction of the force developed by a whole muscle would change when the muscle activity was regionalized within the muscle. A 3D finite element model of a muscle with its bounding aponeurosis was developed for the lateral gastrocnemius, and isometric contractions were simulated for a series of conditions with either a uniform activation pattern, or regionally distinct activation patterns: in all cases the mean activation from all fibers within the muscle reached 10%. The models showed emergent features of the fiber geometry that matched physiological characteristics: with fibers shortening, rotating to greater pennation, adopting curved trajectories in 3D and changes in the thickness and width of the muscle belly. Simulations were repeated for muscle with compliant, normal and stiff aponeurosis and the aponeurosis stiffness affected the changes to the fiber geometry and the resultant muscle force. Changing the regionalization of the activity resulted to changes in the magnitude, direction and center of the force vector from the whole muscle. Regionalizing the muscle activity resulted in greater muscle force than the simulation with uniform activity across the muscle belly. The study shows how the force from a muscle depends on the complex interactions between the muscle fibers and connective tissues and the region of muscle that is active.

  17. Muscle organizers in Drosophila: the role of persistent larval fibers in adult flight muscle development

    NASA Technical Reports Server (NTRS)

    Farrell, E. R.; Fernandes, J.; Keshishian, H.

    1996-01-01

    In many organisms muscle formation depends on specialized cells that prefigure the pattern of the musculature and serve as templates for myoblast organization and fusion. These include muscle pioneers in insects and muscle organizing cells in leech. In Drosophila, muscle founder cells have been proposed to play a similar role in organizing larval muscle development during embryogenesis. During metamorphosis in Drosophila, following histolysis of most of the larval musculature, there is a second round of myogenesis that gives rise to the adult muscles. It is not known whether muscle founder cells organize the development of these muscles. However, in the thorax specific larval muscle fibers do not histolyze at the onset of metamorphosis, but instead serve as templates for the formation of a subset of adult muscles, the dorsal longitudinal flight muscles (DLMs). Because these persistent larval muscle fibers appear to be functioning in many respects like muscle founder cells, we investigated whether they were necessary for DLM development by using a microbeam laser to ablate them singly and in combination. We found that, in the absence of the larval muscle fibers, DLMs nonetheless develop. Our results show that the persistent larval muscle fibers are not required to initiate myoblast fusion, to determine DLM identity, to locate the DLMs in the thorax, or to specify the total DLM fiber volume. However, they are required to regulate the number of DLM fibers generated. Thus, while the persistent larval muscle fibers are not obligatory for DLM fiber formation and differentiation, they are necessary to ensure the development of the correct number of fibers.

  18. Influence of botulinum toxin on rabbit jaw muscle activity and anatomy.

    PubMed

    Korfage, J A M; Wang, Jeffrey; Lie, S H J T J; Langenbach, Geerling E J

    2012-05-01

    Muscles can adapt their fiber properties to accommodate to new conditions. We investigated the extent to which a decrease in muscle activation can cause an adaptation of fiber properties in synergistic and antagonistic jaw muscles. Three months after the injection of botulinum toxin type A in one masseter (anterior or posterior) muscle changes in fiber type composition and fiber cross-sectional areas in jaw muscles were studied at the microscopic level. The injected masseter showed a steep increase in myosin type IIX fibers, whereas fast fibers decreased by about 50% in size. Depending on the injection site, both synergistic and antagonistic muscles showed a significant increase in the size of their fast IIA fibers, sometimes combined with an increased number of IIX fibers. Silencing the activity in the masseter not only causes changes in the fibers of the injected muscle but also leads to changes in other jaw muscles. Copyright © 2012 Wiley Periodicals, Inc.

  19. Comparison of behavior in muscle fiber regeneration after bupivacaine hydrochloride- and acid anhydride-induced myonecrosis.

    PubMed

    Akiyama, C; Kobayashi, S; Nonaka, I

    1992-01-01

    We compared the morphologic characteristics of muscle fiber necrosis and subsequent regeneration after injury induced by intramuscular injections of bupivacaine hydrochloride (BPVC) and a variety of solutions at acid and alkaline pH (acetic anhydride, citric acid buffer, and sodium carbonate buffer). After BPVC injection the necrotic muscle fibers were rapidly invaded by phagocytic cells, followed by active regeneration and very little fibrous scar formation. The regenerating muscle fibers increased rapidly in size and attained complete fiber type differentiation and regained their initial fiber diameter within 1 month. Both alkaline and acid solutions induced muscle fiber necrosis followed by regeneration. Fiber necrosis induced by alkaline buffers and acetic anhydride solutions above pH 5.0 produced changes quite similar to that induced by BPVC. However, injection with 0.1 M acetic anhydride at pH below 4.0 resulted in coagulative necrosis of the injured muscle with very little phagocytic infiltration with poor regenerative activity and dense fibrous tissue scarring. Thus, pH 4.0 appears to be the critical pH determining the type of muscle injury and subsequent poor phagocytic and regenerative activities. This model of acidic acetic anhydride injury may lead to the identification of factors which interfere with regeneration and cause fibrous tissue scarring in human muscular dystrophy.

  20. Evidence for ACTN3 as a Speed Gene in Isolated Human Muscle Fibers.

    PubMed

    Broos, Siacia; Malisoux, Laurent; Theisen, Daniel; van Thienen, Ruud; Ramaekers, Monique; Jamart, Cécile; Deldicque, Louise; Thomis, Martine A; Francaux, Marc

    2016-01-01

    To examine the effect of α-actinin-3 deficiency due to homozygosity for the ACTN3 577X-allele on contractile and morphological properties of fast muscle fibers in non-athletic young men. A biopsy was taken from the vastus lateralis of 4 RR and 4 XX individuals to test for differences in morphologic and contractile properties of single muscle fibers. The cross-sectional area of the fiber and muscle fiber composition was determined using standard immunohistochemistry analyses. Skinned single muscle fibers were subjected to active tests to determine peak normalized force (P0), maximal unloading velocity (V0) and peak power. A passive stretch test was performed to calculate Young's Modulus and hysteresis to assess fiber visco-elasticity. No differences were found in muscle fiber composition. The cross-sectional area of type IIa and IIx fibers was larger in RR compared to XX individuals (P<0.001). P0 was similar in both groups over all fiber types. A higher V0 was observed in type IIa fibers of RR genotypes (P<0.001) but not in type I fibers. The visco-elasticity as determined by Young's Modulus and hysteresis was unaffected by fiber type or genotype. The greater V0 and the larger fast fiber CSA in RR compared to XX genotypes likely contribute to enhanced whole muscle performance during high velocity contractions.

  1. Size and metabolic properties of fibers in rat fast-twitch muscles after hindlimb suspension

    NASA Technical Reports Server (NTRS)

    Roy, Roland R.; Bello, Maureen A.; Bouissou, Phillip; Edgerton, V. Reggie

    1987-01-01

    The effect of hind-limb suspension (HS) on single fibers of the medial gastrocnemius (MG) and the tibialis anterior (TA) muscles were studied in rats. Fiber area and the activities of succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPD) were determined in tissue sections using an image analysis system. After 28 days of HS, the MG atrophied 28 percent, whereas the TA weight was maintained. Both dark- and light-ATPase fibers in the deep region of the MG had decreased cross-sectional areas following HS, with the atrophic response being twice as great in the light-ATPase fibers than in the dark-ATPase fibers. Following HS, mean SDH activities of both fiber types were significantly lower in the MG and TA than in the CON; by contrast, mean GPD activities were either maintained at the CON level or were higher in both MG and TA muscles. The data suggest an independence of the mechanisms determining the muscle fiber size and the metabolic adaptations associated with HS.

  2. Muscle Fiber Orientation Angle Dependence of the Tensile Fracture Behavior of Frozen Fish Muscle

    NASA Astrophysics Data System (ADS)

    Hagura, Yoshio; Okamoto, Kiyoshi; Suzuki, Kanichi; Kubota, Kiyoshi

    We have proposed a new cutting method for frozen fish named "cryo-cutting". This method applied tensile fracture force or bending fracture force to the frozen fish at appropriate low temperatures. In this paper, to clarify cryo-cutting mechanism, we analyzed tensile fracture behavior of the frozen fish muscle. In the analysis, the frozen fish muscle was considered unidirectionally fiber-reinforced composite material which consisted of fiber (muscle fiber) and matrix (connective tissue). Fracture criteria (maximum stress criterion, Tsai-Hill criterion) for the unidirectionally fiber-reinforced composite material were used. The following results were obtained: (1) By using Tsai-Hill criterion, muscle fiber orientation angle dependence of the tensile fracture stress could be calculated. (2) By using the maximum stress theory jointly with Tsai-Hill criterion, muscle fiber orientation angle dependence of the fracture mode of the frozen fish muscle could be estimated.

  3. Unilateral Muscle Overuse Causes Bilateral Changes in Muscle Fiber Composition and Vascular Supply

    PubMed Central

    Song, Yafeng; Forsgren, Sture; Liu, Jing-Xia; Yu, Ji-Guo; Stål, Per

    2014-01-01

    Unilateral strength training can cause cross-transfer strength effects to the homologous contralateral muscles. However, the impact of the cross-over effects on the muscle tissue is unclear. To test the hypothesis that unilateral muscle overuse causes bilateral alterations in muscle fiber composition and vascular supply, we have used an experimental rabbit model with unilateral unloaded overstrain exercise via electrical muscle stimulation (E/EMS). The soleus (SOL) and gastrocnemius (GA) muscles of both exercised (E) and contralateral non-exercised (NE) legs (n = 24) were morphologically analyzed after 1w, 3w and 6w of EMS. Non-exercised rabbits served as controls (n = 6). After unilateral intervention the muscles of both E and NE legs showed myositis and structural and molecular tissue changes that to various degrees mirrored each other. The fiber area was bilaterally smaller than in controls after 3w of E/EMS in both SOL (E 4420 and NE 4333 µm2 vs. 5183 µm2, p<0.05) and GA (E 3572 and NE 2983 µm2 vs. 4697 µm2, p<0.02) muscles. After 6w of E/EMS, the percentage of slow MyHCI fibers was lower than in controls in the NE legs of SOL (88.1% vs. 98.1%, p<0.009), while the percentage of fast MyHCIIa fibers was higher in the NE legs of GA (25.7% vs. 15.8%, p = 0.02). The number of capillaries around fibers in the E and NE legs was lower (SOL 13% and 15%, respectively, GA 25% and 23%, respectively, p<0.05) than in controls. The overall alterations were more marked in the fast GA muscle than in the slow SOL muscle, which on the other hand showed more histopathological muscle changes. We conclude that unilateral repetitive unloaded overuse exercise via EMS causes myositis and muscle changes in fiber type proportions, fiber area and fiber capillarization not only in the exercised leg, but also in the homologous muscles in the non-exercised leg. PMID:25545800

  4. Functional responses of uremic single skeletal muscle fibers to redox imbalances.

    PubMed

    Mitrou, G I; Poulianiti, K P; Koutedakis, Y; Jamurtas, A Z; Maridaki, M D; Stefanidis, I; Sakkas, G K; Karatzaferi, C

    2017-01-01

    The exact causes of skeletal muscle weakness in chronic kidney disease (CKD) remain unknown with uremic toxicity and redox imbalances being implicated. To understand whether uremic muscle has acquired any sensitivity to acute redox changes we examined the effects of redox disturbances on force generation capacity. Permeabilized single psoas fibers (N =37) from surgically induced CKD (UREM) and sham-operated (CON) rabbits were exposed to an oxidizing (10 mM Hydrogen Peroxide, H 2 O 2 ) and/or a reducing [10 mM Dithiothreitol (DTT)] agent, in a blind design, in two sets of experiments examining: A) the acute effect of the addition of H 2 O 2 on maximal (pCa 4.4) isometric force of actively contracting fibers and the effect of incubation in DTT on subsequent re-activation and force recovery (N =9 CON; N =9 UREM fibers); B) the effect of incubation in H 2 O 2 on both submaximal (pCa 6.2) and maximal (pCa 4.4) calcium activated isometric force generation (N =9 CON; N =10 UREM fibers). Based on cross-sectional area (CSA) calculations, a 14 % atrophy in UREM fibers was revealed; thus forces were evaluated in absolute values and corrected for CSA (specific force) values. A) Addition of H 2 O 2 during activation did not significantly affect force generation in any group or the pool of fibers. Incubation in DTT did not affect the CON fibers but caused a 12 % maximal isometric force decrease in UREM fibers (both in absolute force p =0.024, and specific force, p =0.027). B) Incubation in H 2 O 2 during relaxation lowered subsequent maximal (but not submaximal) isometric forces in the Pool of fibers by 3.5 % (for absolute force p =0.033, for specific force p =0.019) but not in the fiber groups separately. Force generation capacity of CON and UREM fibers is affected by oxidation similarly. However, DTT significantly lowered force in UREM muscle fibers. This may indicate that at baseline UREM muscle could have already been at a more reduced redox state than physiological. This

  5. Stiff muscle fibers in calf muscles of patients with cerebral palsy lead to high passive muscle stiffness.

    PubMed

    Mathewson, Margie A; Chambers, Henry G; Girard, Paul J; Tenenhaus, Mayer; Schwartz, Alexandra K; Lieber, Richard L

    2014-12-01

    Cerebral palsy (CP), caused by an injury to the developing brain, can lead to alterations in muscle function. Subsequently, increased muscle stiffness and decreased joint range of motion are often seen in patients with CP. We examined mechanical and biochemical properties of the gastrocnemius and soleus muscles, which are involved in equinus muscle contracture. Passive mechanical testing of single muscle fibers from gastrocnemius and soleus muscle of patients with CP undergoing surgery for equinus deformity showed a significant increase in fiber stiffness (p<0.01). Bundles of fibers that included their surrounding connective tissues showed no stiffness difference (p=0.28).). When in vivo sarcomere lengths were measured and fiber and bundle stiffness compared at these lengths, both fibers and bundles of patients with CP were predicted to be much stiffer in vivo compared to typically developing (TD) individuals. Interestingly, differences in fiber and bundle stiffness were not explained by typical biochemical measures such as titin molecular weight (a giant protein thought to impact fiber stiffness) or collagen content (a proxy for extracellular matrix amount). We suggest that the passive mechanical properties of fibers and bundles are thus poorly understood. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Born to run: creating the muscle fiber.

    PubMed

    Schejter, Eyal D; Baylies, Mary K

    2010-10-01

    From the muscles that control the blink of your eye to those that allow you to walk, the basic architecture of muscle is the same: muscles consist of bundles of the unit muscle cell, the muscle fiber. The unique morphology of the individual muscle fiber is dictated by the functional demands necessary to generate and withstand the forces of contraction, which in turn leads to movement. Contractile muscle fibers are elongated, syncytial cells, which interact with both the nervous and skeletal systems to govern body motion. In this review, we focus on three key cell-cell and cell-matrix contact processes, that are necessary to create this exquisitely specialized cell: cell fusion, cell elongation, and establishment of a myotendinous junction. We address these processes by highlighting recent findings from the Drosophila model system. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Metabolic and morphologic properties of single muscle fibers in the rat after spaceflight, Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Miu, B.; Martin, T. P.; Roy, R. R.; Oganov, V.; Ilyina-Kakueva, E.; Marini, J. F.; Leger, J. J.; Bodine-Fowler, S. C.; Edgerton, V. R.

    1990-01-01

    The adaptation of a slow (soleus, Sol) and a fast (medial gastrocnemius, MG) skeletal muscle to spaceflight was studied in five young male rats. The flight period was 12.5 days and the rats were killed approximately 48 h after returning to 1 g. Five other rats that were housed in cages similar to those used by the flight rats were maintained at 1 g for the same period of time to serve as ground-based controls. Fibers were classified as dark or light staining for myosin adenosine triphosphatase (ATPase). On the average, the fibers in the Sol of the flight rats atrophied twice as much as those in the MG. Further, the fibers located in the deep (close to the bone and having the highest percentage of light ATPase and high oxidative fibers in the muscle cross section) region of the MG atrophied more than the fibers located in the superficial (away from the bone and having the lowest percentage of light ATPase and high oxidative fibers in the muscle cross-section) region of the muscle. Based on quantitative histochemical assays of single muscle fibers, succinate dehydrogenase (SDH) activity per unit volume was unchanged in fibers of the Sol and MG. However, in the Sol, but not the MG, the total amount of SDH activity in a 10-microns-thick section of a fiber decreased significantly in response to spaceflight. Based on population distributions, it appears that the alpha-glycerophosphate dehydrogenase (GPD) activities were elevated in the dark ATPase fibers in the Sol, whereas the light fibers in the Sol and both fiber types in the MG did not appear to change. The ratio of GPD to SDH activities increased in the dark (but not light) fibers of the Sol and was unaffected in the MG. Immunohistochemical analyses indicate that approximately 40% of the fibers in the Sol of flight rats expressed a fast myosin heavy chain compared with 22% in control rats. Further, 31% of the fibers in the Sol of flight rats expressed both fast and slow myosin heavy chains compared with 8% in

  8. Conversion of muscle fiber types in regenerating chicken muscles following cross-reinnervation.

    PubMed

    Kikuchi, T; Akiba, T; Ashmore, C R

    1986-01-01

    Slow-tonic anterior latissimus dorsi (ALD) and fast-twitch posterior latissimus dorsi (PLD) muscles of 7 to 10-day-old White Leghorn chickens were crushed and allowed to be reinnervated by their own nerve, or crushed and transplanted to the other side and allowed to be reinnervated by the nerve of the side to which they were transplanted. Following transplantation, changes in the weight of the muscle, fiber-type composition and innervation pattern during regeneration were investigated. Normal growth rate of PLD was about twice that of ALD. Regenerating PLD, however, atrophied rapidly after crushing and denervation whether innervated by its own nerve or the other nerve type, whereas ALD reinnervated by its own nerve showed marked hypertrophy. PLD fibers transformed rapidly to fast-twitch alpha or slow-tonic (ST) fibers when they were reinnervated by PLD or ALD nerve, respectively. When ALD fibers were reinnervated by their own nerve, they differentiated into ST fibers that were surrounded by smaller immature fibers. ALD fibers were, however, resistant to complete control by fast-twitch PLD nerve and contained a large number of slow fibers (ST and beta) long after transplantation. Slow fibers in regenerates were initially multiply innervated, but later transformed into fast-twitch alpha fibers that were focally innervated. The mode of differentiation and innervation pattern of different muscle fiber types in regenerating muscles are discussed.

  9. Excitation-calcium release uncoupling in aged single human skeletal muscle fibers.

    PubMed

    Delbono, O; O'Rourke, K S; Ettinger, W H

    1995-12-01

    The biological mechanisms underlying decline in muscle power and fatigue with age are not completely understood. The contribution of alterations in the excitation-calcium release coupling in single muscle fibers was explored in this work. Single muscle fibers were voltage-clamped using the double Vaseline gap technique. The samples were obtained by needle biopsy of the vastus lateralis (quadriceps) from 9 young (25-35 years; 25.9 +/- 9.1; 5 female and 4 male) and 11 old subjects (65-75 years; 70.5 +/- 2.3; 6 f, 5 m). Data were obtained from 36 and 39 fibers from young and old subjects, respectively. Subjects included in this study had similar physical activity. Denervated and slow-twitch muscle fibers were excluded from this study. A significant reduction of maximum charge movement (Qmax) and DHP-sensitive Ca current were recorded in muscle fibers from the 65-75 group. Qmax values were 7.6 +/- 0.9 and 3.2 +/- 0.3 nC/muF for young and old muscle fibers, respectively (P < 0.01). No evidences of charge inactivation or interconversion (charge 1 to charge 2) were found. The peak Ca current was (-)4.7 +/- 0.08 and (-)2.15 +/- 0.11 muA/muF for young and old fibers, respectively (P < 0.01). The peak calcium transient studied with mag-fura-2 (400 microM) was 6.3 +/- 0.4 microM and 4.2 +/- 0.3 microM for young and old muscle fibers, respectively. Caffeine (0.5 mM) induced potentiation of the peak calcium transient in both groups. The decrease in the voltage-/Ca-dependent Ca release ratio in old fibers (0.18 +/- 0.02) compared to young fibers (0.47 +/- 0.03) (P < 0.01), was recorded in the absence of sarcoplasmic reticulum calcium depletion. These data support a significant reduction of the amount of Ca available for triggering mechanical responses in aged skeletal muscle and, the reduction of Ca release is due to DHPR-ryanodine receptor uncoupling in fast-twitch fibers. These alterations can account, at least partially for the skeletal muscle function impairment associated

  10. Coupled expression of troponin T and troponin I isoforms in single skeletal muscle fibers correlates with contractility.

    PubMed

    Brotto, Marco A; Biesiadecki, Brandon J; Brotto, Leticia S; Nosek, Thomas M; Jin, Jian-Ping

    2006-02-01

    Striated muscle contraction is powered by actin-activated myosin ATPase. This process is regulated by Ca(2+) via the troponin complex. Slow- and fast-twitch fibers of vertebrate skeletal muscle express type I and type II myosin, respectively, and these myosin isoenzymes confer different ATPase activities, contractile velocities, and force. Skeletal muscle troponin has also diverged into fast and slow isoforms, but their functional significance is not fully understood. To investigate the expression of troponin isoforms in mammalian skeletal muscle and their functional relationship to that of the myosin isoforms, we concomitantly studied myosin, troponin T (TnT), and troponin I (TnI) isoform contents and isometric contractile properties in single fibers of rat skeletal muscle. We characterized a large number of Triton X-100-skinned single fibers from soleus, diaphragm, gastrocnemius, and extensor digitorum longus muscles and selected fibers with combinations of a single myosin isoform and a single class (slow or fast) of the TnT and TnI isoforms to investigate their role in determining contractility. Types IIa, IIx, and IIb myosin fibers produced higher isometric force than that of type I fibers. Despite the polyploidy of adult skeletal muscle fibers, the expression of fast or slow isoforms of TnT and TnI is tightly coupled. Fibers containing slow troponin had higher Ca(2+) sensitivity than that of the fast troponin fibers, whereas fibers containing fast troponin showed a higher cooperativity of Ca(2+) activation than that of the slow troponin fibers. These results demonstrate distinct but coordinated regulation of troponin and myosin isoform expression in skeletal muscle and their contribution to the contractile properties of muscle.

  11. Inhibition of muscle spindle afferent activity during masseter muscle fatigue in the rat.

    PubMed

    Brunetti, Orazio; Della Torre, Giovannella; Lucchi, Maria Luisa; Chiocchetti, Roberto; Bortolami, Ruggero; Pettorossi, Vito Enrico

    2003-09-01

    The influence of muscle fatigue on the jaw-closing muscle spindle activity has been investigated by analyzing: (1) the field potentials evoked in the trigeminal motor nucleus (Vmot) by trigeminal mesencephalic nucleus (Vmes) stimulation, (2) the orthodromic and antidromic responses evoked in the Vmes by stimulation of the peripheral and central axons of the muscle proprioceptive afferents, and (3) the extracellular unitary discharge of masseter muscle spindles recorded in the Vmes. The masseter muscle was fatigued by prolonged tetanic masseter nerve electrical stimulation. Pre- and postsynaptic components of the potentials evoked in the Vmot showed a significant reduction in amplitude following muscle fatigue. Orthodromic and antidromic potentials recorded in the Vmes also showed a similar amplitude decrease. Furthermore, muscle fatigue caused a decrease of the discharge frequency of masseter muscle spindle afferents in most of the examined units. The inhibition of the potential amplitude and discharge frequency was strictly correlated with the extent of muscle fatigue and was mediated by the group III and IV afferent muscle fibers activated by fatigue. In fact, the inhibitory effect was abolished by capsaicin injection in the masseter muscle that provokes selective degeneration of small afferent muscle fibers containing neurokinins. We concluded that fatigue signals originating from the muscle and traveling through capsaicin-sensitive fibers are able to diminish the proprioceptive input by a central presynaptic influence. In the second part of the study, we examined the central projection of the masseter small afferents sensitive to capsaicin at the electron-microscopic level. Fiber degeneration was induced by injecting capsaicin into the masseter muscle. Degenerating terminals were found on the soma and stem process in Vmes and on the dendritic tree of neurons in Vmot. This suggests that small muscle afferents may influence the muscle spindle activity through

  12. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

    PubMed Central

    McCarthy, John J.; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B.; Srikuea, Ratchakrit; Lawson, Benjamin A.; Grimes, Barry; Keller, Charles; Van Zant, Gary; Campbell, Kenneth S.; Esser, Karyn A.; Dupont-Versteegden, Esther E.; Peterson, Charlotte A.

    2011-01-01

    An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells. PMID:21828094

  13. Stretch-induced, steady-state force enhancement in single skeletal muscle fibers exceeds the isometric force at optimum fiber length.

    PubMed

    Rassier, Dilson E; Herzog, Walter; Wakeling, Jennifer; Syme, Douglas A

    2003-09-01

    Stretch-induced force enhancement has been observed in a variety of muscle preparations and on structural levels ranging from single fibers to in vivo human muscles. It is a well-accepted property of skeletal muscle. However, the mechanism causing force enhancement has not been elucidated, although the sarcomere-length non-uniformity theory has received wide support. The purpose of this paper was to re-investigate stretch-induced force enhancement in frog single fibers by testing specific hypotheses arising from the sarcomere-length non-uniformity theory. Single fibers dissected from frog tibialis anterior (TA) and lumbricals (n=12 and 22, respectively) were mounted in an experimental chamber with physiological Ringer's solution (pH=7.5) between a force transducer and a servomotor length controller. The tetantic force-length relationship was determined. Isometric reference forces were determined at optimum length (corresponding to the maximal, active, isometric force), and at the initial and final lengths of the stretch experiments. Stretch experiments were performed on the descending limb of the force-length relationship after maximal tetanic force was reached. Stretches of 2.5-10% (TA) and 5-15% lumbricals of fiber length were performed at 0.1-1.5 fiber lengths/s. The stretch-induced, steady-state, active isometric force was always equal or greater than the purely isometric force at the muscle length from which the stretch was initiated. Moreover, for stretches of 5% fiber length or greater, and initiated near the optimum length of the fiber, the stretch-enhanced active force always exceeded the maximal active isometric force at optimum length. Finally, we observed a stretch-induced enhancement of passive force. We conclude from these results that the sarcomere length non-uniformity theory alone cannot explain the observed force enhancement, and that part of the force enhancement is associated with a passive force that is substantially greater after active

  14. Fiber type conversion by PGC-1α activates lysosomal and autophagosomal biogenesis in both unaffected and Pompe skeletal muscle.

    PubMed

    Takikita, Shoichi; Schreiner, Cynthia; Baum, Rebecca; Xie, Tao; Ralston, Evelyn; Plotz, Paul H; Raben, Nina

    2010-12-13

    PGC-1α is a transcriptional co-activator that plays a central role in the regulation of energy metabolism. Our interest in this protein was driven by its ability to promote muscle remodeling. Conversion from fast glycolytic to slow oxidative fibers seemed a promising therapeutic approach in Pompe disease, a severe myopathy caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA) which is responsible for the degradation of glycogen. The recently approved enzyme replacement therapy (ERT) has only a partial effect in skeletal muscle. In our Pompe mouse model (KO), the poor muscle response is seen in fast but not in slow muscle and is associated with massive accumulation of autophagic debris and ineffective autophagy. In an attempt to turn the therapy-resistant fibers into fibers amenable to therapy, we made transgenic KO mice expressing PGC-1α in muscle (tgKO). The successful switch from fast to slow fibers prevented the formation of autophagic buildup in the converted fibers, but PGC-1α failed to improve the clearance of glycogen by ERT. This outcome is likely explained by an unexpected dramatic increase in muscle glycogen load to levels much closer to those observed in patients, in particular infants, with the disease. We have also found a remarkable rise in the number of lysosomes and autophagosomes in the tgKO compared to the KO. These data point to the role of PGC-1α in muscle glucose metabolism and its possible role as a master regulator for organelle biogenesis - not only for mitochondria but also for lysosomes and autophagosomes. These findings may have implications for therapy of lysosomal diseases and other disorders with altered autophagy.

  15. Fiber number and size in overloaded chicken anterior latissimus dorsi muscle.

    PubMed

    Gollnick, P D; Parsons, D; Riedy, M; Moore, R L

    1983-05-01

    The relative contribution of increases in fiber area and number was evaluated in the chicken anterior latissimus dorsi (ALD) muscle in which enlargement was induced by hanging a weight on one wing. ALD muscles from wings to which weights had been attached for periods ranging from 6 to 65 days weighed an average of 105% (range 22-225%) more than control muscles. Total muscle fiber number, determined by direct counts after nitric acid digestion and fiber dissection, and the frequency of branched fibers were unchanged by muscular enlargement. Fiber cross-sectional area was greater (P less than 0.01) in the enlarged muscles. A close relationship existed (r = 0.78) between actual muscle weight and weight calculated as the product of fiber volume, total fiber number, and muscle density for the control and enlarged muscles. Histochemical staining revealed a conversion of type IIa to type I fibers in the stretched muscles. These results support the concept that skeletal muscle enlargement in response to chronic overload is produced by hypertrophy of preexisting fibers and not be a formation of new fibers.

  16. The effect of different physical activity levels on muscle fiber size and type distribution of lumbar multifidus. A biopsy study on low back pain patient groups and healthy control subjects.

    PubMed

    Mazis, N; Papachristou, D J; Zouboulis, P; Tyllianakis, M; Scopa, C D; Megas, P

    2009-12-01

    Previous studies examining the multifidus fiber characteristics among low back pain (LBP) patients have not considered the variable of physical activity. The present study sought to investigate the muscle fiber size and type distribution of the lumbar multifidus muscle among LBP patient groups with different physical activity levels and healthy controls. Sixty-four patients were assigned to one of three groups named according to the physical activity level, determined for each patient by the International Physical Activity Questionnaire. These were low (LPA), medium (MPA) and high (HPA) physical activity groups. A control group comprising of 17 healthy individuals was also recruited. Muscle biopsy samples were obtained from the multifidus muscle at the level L4-L5. contrast with the control group, LBP patient groups showed a significantly higher Type II fiber distribution as well as reduced diameter in both fiber types (P<0.05). The physical activity level did not have an effect on multifidus characteristics since no significant differences were observed in fiber type and diameter (P>0.05) among LPA, MPA and HPA patient groups. Various pathological conditions were detected which were more pronounced in LBP groups compared to the control (P<0.05). Males had a larger fiber diameter compared to females for both fiber types (P<0.05). The results showed that the level of physical activity did not affect muscle fiber size and type distribution among LBP patients groups. These findings suggest that not only inactivity but also high physical activity levels can have an adverse effect on the multifidus muscle fiber characteristics.

  17. Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

    PubMed Central

    Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

    2017-01-01

    Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

  18. Fiber-type susceptibility to eccentric contraction-induced damage of hindlimb-unloaded rat AL muscles

    NASA Technical Reports Server (NTRS)

    Vijayan, K.; Thompson, J. L.; Norenberg, K. M.; Fitts, R. H.; Riley, D. A.

    2001-01-01

    Slow oxidative (SO) fibers of the adductor longus (AL) were predominantly damaged during voluntary reloading of hindlimb unloaded (HU) rats and appeared explainable by preferential SO fiber recruitment. The present study assessed damage after eliminating the variable of voluntary recruitment by tetanically activating all fibers in situ through the motor nerve while applying eccentric (lengthening) or isometric contractions. Muscles were aldehyde fixed and resin embedded, and semithin sections were cut. Sarcomere lesions were quantified in toluidine blue-stained sections. Fibers were typed in serial sections immunostained with antifast myosin and antitotal myosin (which highlights slow fibers). Both isometric and eccentric paradigms caused fatigue. Lesions occurred only in eccentrically contracted control and HU muscles. Fatigue did not cause lesions. HU increased damage because lesioned- fiber percentages within fiber types and lesion sizes were greater than control. Fast oxidative glycolytic (FOG) fibers were predominantly damaged. In no case did damaged SO fibers predominate. Thus, when FOG, SO, and hybrid fibers are actively lengthened in chronically unloaded muscle, FOG fibers are intrinsically more susceptible to damage than SO fibers. Damaged hybrid-fiber proportions ranged between these extremes.

  19. Partial transformation from fast to slow muscle fibers induced by deafferentation of capsaicin-sensitive muscle afferents.

    PubMed

    Brunetti, O; Barazzoni, A M; Della Torre, G; Clavenzani, P; Pettorossi, V E; Bortolami, R

    1997-11-01

    Mechanical and histochemical characteristics of the lateral gastrocnemius (LG) muscle of the rat were examined 21 days after capsaicin injection into the LG muscle. The capsaicin caused a decrease in generation rate of twitch and tetanic tension and an increase in fatigue resistance of LG muscle. The histochemical muscle fiber profile evaluated by myosin adenosine triphosphatase and reduced nicotinamide adenine dinucleotide tetrazolium reductase methods showed an increase of type I and IIC fibers and a decrease of the type IIB in whole muscle, and a decrease of the IIA, IIX fibers in the red part accompanied by their increase in the white part. Therefore the capsaicin treatment, which selectively eliminated fibers belonging to the III and IV groups of muscle afferents, induced muscle fiber transformation from fast contracting fatiguing fibers to slowly contracting nonfatiguing ones.

  20. Contractile properties of muscle fibers from the deep and superficial digital flexors of horses.

    PubMed

    Butcher, M T; Chase, P B; Hermanson, J W; Clark, A N; Brunet, N M; Bertram, J E A

    2010-10-01

    Equine digital flexor muscles have independent tendons but a nearly identical mechanical relationship to the main joint they act upon. Yet these muscles have remarkable diversity in architecture, ranging from long, unipennate fibers ("short" compartment of DDF) to very short, multipennate fibers (SDF). To investigate the functional relevance of the form of the digital flexor muscles, fiber contractile properties were analyzed in the context of architecture differences and in vivo function during locomotion. Myosin heavy chain (MHC) isoform fiber type was studied, and in vitro motility assays were used to measure actin filament sliding velocity (V(f)). Skinned fiber contractile properties [isometric tension (P(0)/CSA), velocity of unloaded shortening (V(US)), and force-Ca(2+) relationships] at both 10 and 30°C were characterized. Contractile properties were correlated with MHC isoform and their respective V(f). The DDF contained a higher percentage of MHC-2A fibers with myosin (heavy meromyosin) and V(f) that was twofold faster than SDF. At 30°C, P(0)/CSA was higher for DDF (103.5 ± 8.75 mN/mm(2)) than SDF fibers (81.8 ± 7.71 mN/mm(2)). Similarly, V(US) (pCa 5, 30°C) was faster for DDF (2.43 ± 0.53 FL/s) than SDF fibers (1.20 ± 0.22 FL/s). Active isometric tension increased with increasing Ca(2+) concentration, with maximal Ca(2+) activation at pCa 5 at each temperature in fibers from each muscle. In general, the collective properties of DDF and SDF were consistent with fiber MHC isoform composition, muscle architecture, and the respective functional roles of the two muscles in locomotion.

  1. Rapid fast to slow fiber transformation in response to chronic stimulation of immobilized muscles of the rabbit.

    PubMed

    Cotter, M; Phillips, P

    1986-09-01

    Limb immobilization causes muscle atrophy particularly of slow oxidative fibers which also suffer the greatest decrement in neural activation. In this study a fast muscle, tibialis anterior, was chronically stimulated using an activity pattern characteristic of nerve fibers to slow muscles to see whether or not this could prevent immobilization induced slow fiber atrophy. Four groups of rabbits were used: unoperated controls, stimulated (10 Hz, 8 h/day), immobilized (neutral position), and a stimulated plus immobilized group. The experimental period was 28 to 30 days or 44 to 50 days. Immobilization caused significant decrease in slow oxidative fiber area which was completely prevented by stimulation. In animals tested for the longer period there was 56% hypertrophy. In addition, the combination of stimulation and immobilization caused a two-fold increase in the number of slow oxidative fibers and greatly increased the proportion of intermediate fibers. Stimulation without immobilization had no effect. Slow fibers in stimulated immobilized muscles had a bimodal area distribution; the number of large fibers (mean area 7059 micron2) was the same as the number of slow oxidative fibers in contralateral muscles, suggesting that they were the preexisting slow fibers, and a small fiber population (mean area 3143 micron2) represented newly converted fast fibers. We conclude that slow muscle units benefit from restoration of activity by chronic stimulation. In addition, the combination of stimulation and immobilization accelerates fast to slow fiber conversion. We suggest that isometric conditions as well as enhanced glucocorticoid effects could account for these findings.

  2. Adaptation of rat jaw muscle fibers in postnatal development with a different food consistency: an immunohistochemical and electromyographic study.

    PubMed

    Kawai, Nobuhiko; Sano, Ryota; Korfage, Joannes A M; Nakamura, Saika; Kinouchi, Nao; Kawakami, Emi; Tanne, Kazuo; Langenbach, Geerling E J; Tanaka, Eiji

    2010-06-01

    The development of the craniofacial system occurs, among other reasons, as a response to functional needs. In particular, the deficiency of the proper masticatory stimulus affects the growth. The purpose of this study was to relate alterations of muscle activity during postnatal development to adaptational changes in the muscle fibers. Fourteen 21-day-old Wistar strain male rats were randomly divided into two groups and fed on either a solid (hard-diet group) or a powder (soft-diet group) diet for 63 days. A radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter, anterior belly of digastric and anterior temporalis muscles. The degree of daily muscle use was quantified by the total duration of muscle activity per day (duty time), the total burst number and their average length exceeding specified levels of the peak activity (5, 20 and 50%). The fiber type composition of the muscles was examined by the myosin heavy chain content of fibers by means of immunohistochemical staining and their cross-sectional area was measured. All muscle fibers were identified as slow type I and fast type IIA, IIX or IIB (respectively, with increasing twitch contraction speed and fatigability). At lower activity levels (exceeding 5% of the peak activity), the duty time of the anterior belly of the digastric muscle was significantly higher in the soft-diet group than in the hard-diet group (P < 0.05). At higher activity levels (exceeding 20 and 50% of the peak activity), the duty time of the superficial masseter muscle in the soft-diet group was significantly lower than that in the hard-diet group (P < 0.05). There was no difference in the duty time of the anterior temporalis muscle at any muscle activity level. The percentage of type IIA fibers of the superficial masseter muscle in the soft-diet group was significantly lower than that in the hard-diet group (P < 0.01) and the opposite was true with regard to type IIB fibers (P < 0

  3. Relationships among muscle fiber type composition, fiber diameter and MRF gene expression in different skeletal muscles of naturally grazing Wuzhumuqin sheep during postnatal development.

    PubMed

    Siqin, Qimuge; Nishiumi, Tadayuki; Yamada, Takahisa; Wang, Shuiqing; Liu, Wenjun; Wu, Rihan; Borjigin, Gerelt

    2017-12-01

    The aim of this study was to determine the relationships among muscle fiber-type composition, fiber diameter, and myogenic regulatory factor (MRF) gene expression in different skeletal muscles during development in naturally grazing Wuzhumuqin sheep. Three major muscles (i.e. the Longissimus dorsi (LD), Biceps femoris (BF) and Triceps brachii (TB)) were obtained from 20 Wuzhumuqin sheep and 20 castrated rams at each of the following ages: 1, 3, 6, 9, 12 and 18 months. Muscle fiber-type composition and fiber diameter were measured using histochemistry and morphological analysis, and MRF gene expression levels were determined using real-time PCR. In the LD muscle, changes in the proportion of each of different types of fiber (I, IIA and IIB) were relatively small. In the BF muscle, a higher proportion of type I and a 6.19-fold lower proportion of type IIA fibers were observed (P < 0.05). In addition, the compositions of type I and IIA fibers continuously changed in the TB muscle (P < 0.05). Moreover, muscle diameter gradually increased throughout development (P < 0.05). Almost no significant difference was found in MRF gene expression patterns, which appeared to be relatively stable. These results suggest that changes in fiber-type composition and increases in fiber size may be mutually interacting processes during muscle development. © 2017 The Authors Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

  4. Assessment of the Contractile Properties of Permeabilized Skeletal Muscle Fibers.

    PubMed

    Claflin, Dennis R; Roche, Stuart M; Gumucio, Jonathan P; Mendias, Christopher L; Brooks, Susan V

    2016-01-01

    Permeabilized individual skeletal muscle fibers offer the opportunity to evaluate contractile behavior in a system that is greatly simplified, yet physiologically relevant. Here we describe the steps required to prepare, permeabilize and preserve small samples of skeletal muscle. We then detail the procedures used to isolate individual fiber segments and attach them to an experimental apparatus for the purpose of controlling activation and measuring force generation. We also describe our technique for estimating the cross-sectional area of fiber segments. The area measurement is necessary for normalizing the absolute force to obtain specific force, a measure of the intrinsic force-generating capability of the contractile system.

  5. Fiber-type distribution in insect leg muscles parallels similarities and differences in the functional role of insect walking legs.

    PubMed

    Godlewska-Hammel, Elzbieta; Büschges, Ansgar; Gruhn, Matthias

    2017-10-01

    Previous studies have demonstrated that myofibrillar ATPase (mATPase) enzyme activity in muscle fibers determines their contraction properties. We analyzed mATPase activities in muscles of the front, middle and hind legs of the orthopteran stick insect (Carausius morosus) to test the hypothesis that differences in muscle fiber types and distributions reflected differences in their behavioral functions. Our data show that all muscles are composed of at least three fiber types, fast, intermediate and slow, and demonstrate that: (1) in the femoral muscles (extensor and flexor tibiae) of all legs, the number of fast fibers decreases from proximal to distal, with a concomitant increase in the number of slow fibers. (2) The swing phase muscles protractor coxae and levator trochanteris, have smaller percentages of slow fibers compared to the antagonist stance muscles retractor coxae and depressor trochanteris. (3) The percentage of slow fibers in the retractor coxae and depressor trochanteris increases significantly from front to hind legs. These results suggest that fiber-type distribution in leg muscles of insects is not identical across leg muscles but tuned towards the specific function of a given muscle in the locomotor system.

  6. Coupled expression of troponin T and troponin I isoforms in single skeletal muscle fibers correlates with contractility

    PubMed Central

    BROTTO, MARCO A.; BIESIADECKI, BRANDON J.; BROTTO, LETICIA S.; NOSEK, THOMAS M; JIN, J.-P.

    2005-01-01

    (Summary) Brotto, Marco A., Brandon J. Biesiadecki, Leticia S. Brotto, Thomas M. Nosek, and J.-P. Jin. Striated muscle contraction is powered by actin-activated myosin ATPase. This process is regulated by Ca2+ via the troponin complex. Slow and fast twitch fibers of vertebrate skeletal muscle express type I and type II myosin, respectively, and these myosin isoenzymes confer different ATPase activities, contractile velocities and force. Skeletal muscle troponin has also diverged into fast and slow isoforms, but their functional significance is not fully understood. To investigate the expression of troponin isoforms in mammalian skeletal muscle and their functional relationship to that of the myosin isoforms, we concomitantly studied myosin and troponin T (TnT) and troponin I (TnI) isoform contents and isometric contractile properties in single fibers of rat skeletal muscle. We characterized a large number of Triton skinned single fibers from soleus, diaphragm, gastrocnemius and extensor digitorum longus muscles and selected fibers with combinations of a single myosin isoform and a single class (slow or fast) of TnT and TnI isoform to investigate their role in determining contractility. Type IIa, IIx and IIb myosin fibers produced higher isometric force than that of type I fibers. Despite the polyploidy of adult skeletal muscle fibers, the expression of fast or slow isoforms of TnT and TnI is tightly coupled. Fibers containing slow troponin had higher Ca2+ sensitivity than that of the fast troponin fibers, while fibers containing fast troponin showed a higher cooperativity of Ca2+ activation than that of the slow troponin fibers. The results demonstrate distinctive, but coordinated, regulation of troponin and myosin isoform expression in skeletal muscle and their contribution to the contractile properties. PMID:16192301

  7. Pathophysiology of muscle fiber necrosis induced by bupivacaine hydrochloride (Marcaine).

    PubMed

    Nonaka, I; Takagi, A; Ishiura, S; Nakase, H; Sugita, H

    1983-01-01

    A single direct injection of a local anesthetic, 0.5% bupivacaine hydrochloride (BPVC) (Marcaine), into rat soleus and extensor digitorum longus (EDL) muscles produced massive fiber necrosis with extensive phagocytosis followed by rapid regeneration, predominantly in the soleus. Since the sarcoplasmic reticulum (SR) was functionally disturbed by BPVC administration as confirmed by an in vitro study, the sarcolemmal lysis seen in the early phase of degeneration was not assumed to simply result from direct damage to the plasma membrane caused by BPVC. The extracellular fluid containing a high concentration of calcium (Ca) ions then permeated into the sarcoplasm through the defective membrane resulting in hyper-contracted myofibrils. Selective damage to the Z-line, an early sign of muscle degeneration, was shown by electron microscopy and SDS gel electrophoresis (preferential loss of alpha-actinin). Administration of leupeptin, a thiol protease inhibitor, proved to be ineffective in inhibiting the necrotic process, because the BPVC induced muscle fiber breakdown was probably too acute and fulminant to demonstrate the inhibitory effect upon the degenerative process. Well preserved satellite cells, peripheral nerves, and acetylcholinesterase activity, and the absence of fibrous tissue proliferation in this system may be responsible for the extremely rapid regeneration with complete muscle fiber type differentiation. Since the sequence of fiber breakdown induced by BPVC administration was similar to that of progressive muscular dystrophy, this chemical will be one of the most useful tools for studying the pathophysiology of fiber necrosis and regeneration in diseased muscle.

  8. Muscle fiber types composition and type identified endplate morphology of forepaw intrinsic muscles in the rat.

    PubMed

    Pan, Feng; Mi, Jing-Yi; Zhang, Yan; Pan, Xiao-Yun; Rui, Yong-Jun

    2016-06-01

    The failure to accept reinnervation is considered to be one of the reasons for the poor motor functional recovery of intrinsic hand muscles (IHMs) after nerve injury. Rat could be a suitable model to be used in simulating motor function recovery of the IHMs after nerve injury as to the similarities in function and anatomy of the muscles between human and rat. However, few studies have reported the muscle fiber types composition and endplate morphologic characteristics of intrinsic forepaw muscles (IFMs) in the rat. In this study, the myosin heavy chain isoforms and acetylcholine receptors were stained by immunofluorescence to show the muscle fiber types composition and endplates on type-identified fibers of the lumbrical muscles (LMs), interosseus muscles (IMs), abductor digiti minimi (AM) and flexor pollicis brevis (FM) in rat forepaw. The majority of IFMs fibers were labeled positively for fast-switch fiber. However, the IMs were composed of only slow-switch fiber. With the exception of the IMs, the other IFMs had a part of hybrid fibers. Two-dimensional morphological characteristics of endplates on I and IIa muscle fiber had no significant differences among the IFMs. The LMs is the most suitable IFMs of rat to stimulate reinnervation of the IHMs after nerve injury. Gaining greater insight into the muscle fiber types composition and endplate morphology in the IFMs of rat may help understand the pathological and functional changes of IFMs in rat model stimulating reinnervation of IHMs after peripheral nerve injury.

  9. Common errors in textbook descriptions of muscle fiber size in nontrained humans.

    PubMed

    Chalmers, Gordon R; Row, Brandi S

    2011-09-01

    Exercise science and human anatomy and physiology textbooks commonly report that type IIB muscle fibers have the largest cross-sectional area of the three fiber types. These descriptions of muscle fiber sizes do not match with the research literature examining muscle fibers in young adult nontrained humans. For men, most commonly type IIA fibers were significantly larger than other fiber types (six out of 10 cases across six different muscles). For women, either type I, or both I and IIA muscle fibers were usually significantly the largest (five out of six cases across four different muscles). In none of these reports were type IIB fibers significantly larger than both other fiber types. In 27 studies that did not include statistical comparisons of mean fiber sizes across fiber types, in no cases were type IIB or fast glycolytic fibers larger than both type I and IIA, or slow oxidative and fast oxidative glycolytic fibers. The likely reason for mistakes in textbook descriptions of human muscle fiber sizes is that animal data were presented without being labeled as such, and without any warning that there are interspecies differences in muscle fiber properties. Correct knowledge of muscle fiber sizes may facilitate interpreting training and aging adaptations.

  10. Stiffness and force in activated frog skeletal muscle fibers.

    PubMed Central

    Cecchi, G.; Griffiths, P. J.; Taylor, S.

    1986-01-01

    Single fibers, isolated intact from frog skeletal muscles, were held firmly very near to each end by stiff metal clasps fastened to the tendons. The fibers were then placed horizontally between two steel hooks inserted in eyelets of the tendon clasps. One hook was attached to a capacitance gauge force transducer (resonance frequency up to approximately 50 kHz) and the other was attached to a moving-coil length changer. This allowed us to impose small, rapid releases (complete in less than 0.15 ms) and high frequency oscillations (up to 13 kHz) to one end of a resting or contracting fiber and measure the consequences at the other end with fast time resolution at 4 to 6 degrees C. The stiffness of short fibers (1.8-2.6 mm) was determined directly from the ratio of force to length variations produced by the length changer. The resonance frequency of short fibers was so high (approximately 40 kHz) that intrinsic oscillations were not detectably excited. The stiffness of long fibers, on the other hand, was calculated from measurement of the mechanical resonance frequency of a fiber. Using both short and long fibers, we measured the sinusoids of force at one end of a contracting fiber that were produced by relatively small sinusoidal length changes at the other end. The amplitudes of the sinusoidal length changes were small compared with the size of step changes that produce nonlinear force-extension relations. The sinusoids of force from long fibers changed amplitude and shifted phase with changes in oscillation frequency in a manner expected of a transmission line composed of mass, compliance, and viscosity, similar to that modelled by (Ford, L. E., A. F. Huxley, and R. M. Simmons, 1981, J. Physiol. (Lond.), 311:219-249). A rapid release during the plateau of tetanic tension in short fibers caused a fall in force and stiffness, a relative change in stiffness that putatively was much smaller than that of force. Our results are, for the most part, consistent with the

  11. Spermine oxidase maintains basal skeletal muscle gene expression and fiber size and is strongly repressed by conditions that cause skeletal muscle atrophy

    PubMed Central

    Bongers, Kale S.; Fox, Daniel K.; Kunkel, Steven D.; Stebounova, Larissa V.; Murry, Daryl J.; Pufall, Miles A.; Ebert, Scott M.; Dyle, Michael C.; Bullard, Steven A.; Dierdorff, Jason M.

    2014-01-01

    Skeletal muscle atrophy is a common and debilitating condition that remains poorly understood at the molecular level. To better understand the mechanisms of muscle atrophy, we used mouse models to search for a skeletal muscle protein that helps to maintain muscle mass and is specifically lost during muscle atrophy. We discovered that diverse causes of muscle atrophy (limb immobilization, fasting, muscle denervation, and aging) strongly reduced expression of the enzyme spermine oxidase. Importantly, a reduction in spermine oxidase was sufficient to induce muscle fiber atrophy. Conversely, forced expression of spermine oxidase increased muscle fiber size in multiple models of muscle atrophy (immobilization, fasting, and denervation). Interestingly, the reduction of spermine oxidase during muscle atrophy was mediated by p21, a protein that is highly induced during muscle atrophy and actively promotes muscle atrophy. In addition, we found that spermine oxidase decreased skeletal muscle mRNAs that promote muscle atrophy (e.g., myogenin) and increased mRNAs that help to maintain muscle mass (e.g., mitofusin-2). Thus, in healthy skeletal muscle, a relatively low level of p21 permits expression of spermine oxidase, which helps to maintain basal muscle gene expression and fiber size; conversely, during conditions that cause muscle atrophy, p21 expression rises, leading to reduced spermine oxidase expression, disruption of basal muscle gene expression, and muscle fiber atrophy. Collectively, these results identify spermine oxidase as an important positive regulator of muscle gene expression and fiber size, and elucidate p21-mediated repression of spermine oxidase as a key step in the pathogenesis of skeletal muscle atrophy. PMID:25406264

  12. Thyroid hormone regulates muscle fiber type conversion via miR-133a1.

    PubMed

    Zhang, Duo; Wang, Xiaoyun; Li, Yuying; Zhao, Lei; Lu, Minghua; Yao, Xuan; Xia, Hongfeng; Wang, Yu-Cheng; Liu, Mo-Fang; Jiang, Jingjing; Li, Xihua; Ying, Hao

    2014-12-22

    It is known that thyroid hormone (TH) is a major determinant of muscle fiber composition, but the molecular mechanism by which it does so remains unclear. Here, we demonstrated that miR-133a1 is a direct target gene of TH in muscle. Intriguingly, miR-133a, which is enriched in fast-twitch muscle, regulates slow-to-fast muscle fiber type conversion by targeting TEA domain family member 1 (TEAD1), a key regulator of slow muscle gene expression. Inhibition of miR-133a in vivo abrogated TH action on muscle fiber type conversion. Moreover, TEAD1 overexpression antagonized the effect of miR-133a as well as TH on muscle fiber type switch. Additionally, we demonstrate that TH negatively regulates the transcription of myosin heavy chain I indirectly via miR-133a/TEAD1. Collectively, we propose that TH inhibits the slow muscle phenotype through a novel epigenetic mechanism involving repression of TEAD1 expression via targeting by miR-133a1. This identification of a TH-regulated microRNA therefore sheds new light on how TH achieves its diverse biological activities. © 2014 Zhang et al.

  13. Thyroid hormone regulates muscle fiber type conversion via miR-133a1

    PubMed Central

    Zhang, Duo; Wang, Xiaoyun; Li, Yuying; Zhao, Lei; Lu, Minghua; Yao, Xuan; Xia, Hongfeng; Wang, Yu-cheng; Liu, Mo-Fang; Jiang, Jingjing; Li, Xihua

    2014-01-01

    It is known that thyroid hormone (TH) is a major determinant of muscle fiber composition, but the molecular mechanism by which it does so remains unclear. Here, we demonstrated that miR-133a1 is a direct target gene of TH in muscle. Intriguingly, miR-133a, which is enriched in fast-twitch muscle, regulates slow-to-fast muscle fiber type conversion by targeting TEA domain family member 1 (TEAD1), a key regulator of slow muscle gene expression. Inhibition of miR-133a in vivo abrogated TH action on muscle fiber type conversion. Moreover, TEAD1 overexpression antagonized the effect of miR-133a as well as TH on muscle fiber type switch. Additionally, we demonstrate that TH negatively regulates the transcription of myosin heavy chain I indirectly via miR-133a/TEAD1. Collectively, we propose that TH inhibits the slow muscle phenotype through a novel epigenetic mechanism involving repression of TEAD1 expression via targeting by miR-133a1. This identification of a TH-regulated microRNA therefore sheds new light on how TH achieves its diverse biological activities. PMID:25512392

  14. Change in the contractile behavior of muscle fibers in subjects with primary muscle dysfunction.

    PubMed

    Back, Claudio Gregório Nuernberg; Benedini-Elias, Priscila C O; Mattiello, Stela M; Sobreira, Claudia; Martinez, Edson Z; Mattiello-Sverzut, Ana Claudia

    2013-01-01

    The mechanical and metabolic characteristics of skeletal muscle fibers can interfere with muscle contractile performance in healthy subjects. Few studies have investigated the degree of association between muscle function and muscle fiber morphology in patients with myopathy. A biopsy was obtained from the left biceps brachii muscle of 12 subjects with myopathic disorders. The relative cross-sectional area of type 2 fibers and their subtypes was determined by the ATPase technique. Relative torque (RT) was calculated by dividing isokinetic elbow flexion peak torque (PT) values (90 and 180° s-1) by isometric PT values. Correlations were analyzed using Spearman's coefficient (r). The relative cross-sectional area of type 2b fibers was positively correlated with RT90 (r = 0.71, P = 0.009) and RT180 (r = 0.73, P = 0.007). The relative cross-sectional area of type 2a fibers showed a moderate and negative correlation with RT180 (r = -0.62, P = 0.03) and a low correlation with RT90 (r = -0.57, P = 0.05). In contrast to healthy subjects, patients with myopathy presented changes in the contractile behavior of type 2a fibers and compensatory adaptations in type 2b fibers. The results suggest that RT in combination with morphometric parameters provides data regarding muscle function in patients with myopathic disorders and can contribute to the establishment of therapeutic exercises.

  15. Lauric Acid Accelerates Glycolytic Muscle Fiber Formation through TLR4 Signaling.

    PubMed

    Wang, Leshan; Luo, Lv; Zhao, Weijie; Yang, Kelin; Shu, Gang; Wang, Songbo; Gao, Ping; Zhu, Xiaotong; Xi, Qianyun; Zhang, Yongliang; Jiang, Qingyan; Wang, Lina

    2018-06-18

    Lauric acid (LA), which is the primary fatty acid in coconut oil, was reported to have many metabolic benefits. TLR4 is a common receptor of lipopolysaccharides and involved mainly in inflammation responses. Here, we focused on the effects of LA on skeletal muscle fiber types and metabolism. We found that 200 μM LA treatment in C2C12 or dietary supplementation of 1% LA increased MHCIIb protein expression and the proportion of type IIb muscle fibers from 0.452 ± 0.0165 to 0.572 ± 0.0153, increasing the mRNA expression of genes involved in glycolysis, such as HK2 and LDH2 (from 1.00 ± 0.110 to 1.35 ± 0.0843 and from 1.00 ± 0.123 to 1.71 ± 0.302 in vivo, respectively), decreasing the catalytic activity of lactate dehydrogenase (LDH), and transforming lactic acid to pyruvic acid. Furthermore, LA activated TLR4 signaling, and TLR4 knockdown reversed the effect of LA on muscle fiber type and glycolysis. Thus, we inferred that LA promoted glycolytic fiber formation through TLR4 signaling.

  16. Morphology of the lumbar transversospinal muscles examined in a mouse bearing a muscle fiber-specific nuclear marker.

    PubMed

    Cornwall, Jon; Deries, Marianne; Duxson, Marilyn

    2010-12-01

    Although the morphology of human lumbar transversospinal (TSP) muscles has been studied, little is known about the structure of these muscles in the mouse (Mus musculus). Such information is relevant given mice are often used as a "normal" phenotype for studies modeling human development. This study describes the gross morphology, muscle fiber arrangement, and innervation pattern of the mouse lumbar TSP muscles. A unique feature of the study is the use of a transgenic mouse line bearing a muscle-specific nuclear marker that allows clear delineation of muscle fiber and connective tissue boundaries. The lumbar TSP muscles of five mice were examined bilaterally; at each spinal level muscles attached to the caudal edge of the spinous process and passed caudally as a single complex unit. Fibers progressively terminated over the four vertebral segments caudad, with multiple points of muscle fiber attachment on each vertebra. Motor endplates, defined with acetylcholinesterase histochemistry, were consistently located half way along each muscle fiber, regardless of length, with all muscle fibers arranged in-parallel rather than in-series. These results provide information relevant to interpretation of developmental and functional studies involving this muscle group in the mouse and show mouse lumbar TSP muscles are different in form to descriptions of equivalent muscles in humans and horses.

  17. [Alteration of metabolic characteristics on the masseter muscle fiber of unilateral chewing rats and its adenosine monophosphate activated protein kinase regulatory mechanism].

    PubMed

    Andi, Shi; Lin, Zeng; Jing, Liu

    2017-06-01

    This study aims to determine the influence of unilateral chewing on metabolic characteristics of masseter muscle fibers in rats and the regulatory effect of an adenosine monophosphate activated protein kinase (AMPK) signal pathway on metabolism. Rats were submitted to exodontia of all the right maxillary molars and divided into 2, 4, 6, and 8 weeks groups, and corresponding control groups were set as well. Sections were stained by nicotine adenine dinucleotide tetrazolim reductase(NADH-TRase) to demonstrate the types, proportion, and density of masseter muscle fibers. AMPKα1 and p-AMPK(Thr172) levels in bilateral masseter muscles were detected by Western blot. In the 2-week group, the percentage of dark fibers augmented in the ipsilateral side, whereas the percentage of intermediary fibers in the contralateral side was increased accompanied by a decrease of light fibers, compared with the control group (P<0.05). The percentage of dark fibers was increased in the bilateral sides, whereas the percentage of dark fiber in the ipsilateral sides surpassed that of the contralateral sides in the 4, 6, and 8-week groups. The percentage of intermediary fibers was decreased in the bilateral sides in the 6 and 8-week groups (P<0.05). The percentage of light fibers was reduced in the ipsilateral sides in the 8-week group, whereas no alteration was observed in contralateral sides (P>0.05). In the ipsilateral sides, p-AMPK (Thr172)/AMPKα1 levels were increased in the 2 and 4-week groups (P<0.05), whereas no change was observed in the contralateral sides in either group (P>0.05). Unilateral chewing increases the oxidative metabolic ability in bilateral masseter muscle fibers especially in the non-working side accompanied with change of muscle fiber types. The improvement of aerobic metabolism ability is related to the AMPK signal pathway.
.

  18. Morphological classification and comparison of suboccipital muscle fiber characteristics

    PubMed Central

    Yamamoto, Masahito; Kitamura, Kei; Morita, Sumiharu; Nagakura, Ryotaro; Matsunaga, Satoru; Abe, Shinichi

    2017-01-01

    In an attempt to clarify the function of the suboccipital muscles, we performed morphological observation of the suboccipital muscles for variations in the muscle belly and compared the morphology of their muscle fibers in terms of cross-sectional area by immunostaining with anti-myosin heavy chain antibodies. The cadavers of 25 Japanese individuals were used: 22 for morphological examinations and three for histological examinations. Among samples of the rectus capitis posterior major muscle (RCPma) and rectus capitis posterior minor muscle (RCPmi), 86.4% had a typical muscle appearance with a single belly, and 13.6% had an anomalous morphology. None of the samples of the obliquus capitis superior (OCS) or obliquus capitis inferior (OCI) muscles had an anomalous appearance. Measurement of cross-sectional area revealed that fast-twitch muscle fibers in the RCPma and OCI had a significantly greater cross-sectional area than those of the RCPmi and OCS. The cross-sectional area of intermediate muscle fibers was also significantly greater in the OCS than in the RCPma, RCPmi, and OCI. The cross-sectional area of slow-twitch muscle fibers was significantly greater in the OCS than in the RCPma, RCPmi, and OCI, and the RCPmi showed a significantly greater cross-sectional area for slow-twitch muscle fibers than did the RCPma, and OCI. Our findings indicate that the RCPmi and OCS exert a greater force than the RCPma and OCI, and act as anti-gravity agonist muscles of the head. Prolonged head extension in individuals with anomalous suboccipital muscle groups could result in dysfunction due to undue stress. PMID:29354295

  19. Morphological classification and comparison of suboccipital muscle fiber characteristics.

    PubMed

    Yamauchi, Masato; Yamamoto, Masahito; Kitamura, Kei; Morita, Sumiharu; Nagakura, Ryotaro; Matsunaga, Satoru; Abe, Shinichi

    2017-12-01

    In an attempt to clarify the function of the suboccipital muscles, we performed morphological observation of the suboccipital muscles for variations in the muscle belly and compared the morphology of their muscle fibers in terms of cross-sectional area by immunostaining with anti-myosin heavy chain antibodies. The cadavers of 25 Japanese individuals were used: 22 for morphological examinations and three for histological examinations. Among samples of the rectus capitis posterior major muscle (RCPma) and rectus capitis posterior minor muscle (RCPmi), 86.4% had a typical muscle appearance with a single belly, and 13.6% had an anomalous morphology. None of the samples of the obliquus capitis superior (OCS) or obliquus capitis inferior (OCI) muscles had an anomalous appearance. Measurement of cross-sectional area revealed that fast-twitch muscle fibers in the RCPma and OCI had a significantly greater cross-sectional area than those of the RCPmi and OCS. The cross-sectional area of intermediate muscle fibers was also significantly greater in the OCS than in the RCPma, RCPmi, and OCI. The cross-sectional area of slow-twitch muscle fibers was significantly greater in the OCS than in the RCPma, RCPmi, and OCI, and the RCPmi showed a significantly greater cross-sectional area for slow-twitch muscle fibers than did the RCPma, and OCI. Our findings indicate that the RCPmi and OCS exert a greater force than the RCPma and OCI, and act as anti-gravity agonist muscles of the head. Prolonged head extension in individuals with anomalous suboccipital muscle groups could result in dysfunction due to undue stress.

  20. Gene polymorphisms and fiber-type composition of human skeletal muscle.

    PubMed

    Ahmetov, Ildus I; Vinogradova, Olga L; Williams, Alun G

    2012-08-01

    The ability to perform aerobic or anaerobic exercise varies widely among individuals, partially depending on their muscle-fiber composition. Variability in the proportion of skeletal-muscle fiber types may also explain marked differences in aspects of certain chronic disease states including obesity, insulin resistance, and hypertension. In untrained individuals, the proportion of slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around 50% (range 5-90%), and it is unusual for them to undergo conversion to fast-twitch fibers. It has been suggested that the genetic component for the observed variability in the proportion of Type I fibers in human muscles is on the order of 40-50%, indicating that muscle fiber-type composition is determined by both genotype and environment. This article briefly reviews current progress in the understanding of genetic determinism of fiber-type proportion in human skeletal muscle. Several polymorphisms of genes involved in the calcineurin-NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia and angiogenesis, and circulatory homeostasis have been associated with fiber-type composition. As muscle is a major contributor to metabolism and physical strength and can readily adapt, it is not surprising that many of these gene variants have been associated with physical performance and athlete status, as well as metabolic and cardiovascular diseases. Genetic variants associated with fiber-type proportions have important implications for our understanding of muscle function in both health and disease.

  1. Recruitment of single muscle fibers during submaximal cycling exercise.

    PubMed

    Altenburg, T M; Degens, H; van Mechelen, W; Sargeant, A J; de Haan, A

    2007-11-01

    In literature, an inconsistency exists in the submaximal exercise intensity at which type II fibers are activated. In the present study, the recruitment of type I and II fibers was investigated from the very beginning and throughout a 45-min cycle exercise at 75% of the maximal oxygen uptake, which corresponded to 38% of the maximal dynamic muscle force. Biopsies of the vastus lateralis muscle were taken from six subjects at rest and during the exercise, two at each time point. From the first biopsy single fibers were isolated and characterized as type I and II, and phosphocreatine-to-creatine (PCr/Cr) ratios and periodic acid-Schiff (PAS) stain intensities were measured. Cross sections were cut from the second biopsy, individual fibers were characterized as type I and II, and PAS stain intensities were measured. A decline in PCr/Cr ratio and in PAS stain intensity was used as indication of fiber recruitment. Within 1 min of exercise both type I and, although to a lesser extent, type II fibers were recruited. Furthermore, the PCr/Cr ratio revealed that the same proportion of fibers was recruited during the whole 45 min of exercise, indicating a rather constant recruitment. The PAS staining, however, proved inadequate to fully demonstrate fiber recruitment even after 45 min of exercise. We conclude that during cycling exercise a greater proportion of type II fibers is recruited than previously reported for isometric contractions, probably because of the dynamic character of the exercise. Furthermore, the PCr/Cr ratio method is more sensitive in determining fiber activation than the PAS stain intensity method.

  2. Spaceflight and growth effects on muscle fibers in the rhesus monkey

    NASA Technical Reports Server (NTRS)

    Bodine-Fowler, Sue C.; Roy, Roland R.; Rudolph, William; Haque, Naz; Kozlovskaia, Inessa B.; Edgerton, V. R.

    1992-01-01

    The effect of a 14-day spaceflight onboard Cosmos 2044 on selected morphological and metabolic properties of single muscle fibers was investigated in a nonhuman primate, Macaca mulatta. It is concluded that the 14-day spaceflight had little impact on fiber size in the soleus (S) and medial gastrocnemius (MG) muscles, whereas it appeared to be a slight decrease in sized in the tibialis anterior (TA). The mean fiber size in the postflight biopsies increased relative to preflight values. The mean fiber succinate dehydrogenase activity was found to decrease in the MG, whereas there was no apparent effect of spaceflight on the s and ta muscles. The differences in response of the S, MG, and TA to spaceflight in monkeys vs rats may be related to a species responsiveness to spaceflight, the manner in which the animals were restrained, and/or the possibility that the ankle musculature was able to function against a load while in space.

  3. Fiber optic biofluorometer for physiological research on muscle slices

    NASA Astrophysics Data System (ADS)

    Belz, Mathias; Dendorfer, Andreas; Werner, Jan; Lambertz, Daniel; Klein, Karl-Friedrich

    2016-03-01

    A focus of research in cell physiology is the detection of Ca2+, NADH, FAD, ATPase activity or membrane potential, only to name a few, in muscle tissues. In this work, we report on a biofluorometer using ultraviolet light emitting diodes (UV-LEDs), optical fibers and two photomultipliers (PMTs) using synchronized fluorescence detection with integrated background correction to detect free calcium, Ca2+, in cardiac muscle tissue placed in a horizontal tissue bath and a microscope setup. Fiber optic probes with imaging optics have been designed to transport excitation light from the biofluorometer's light output to a horizontal tissue bath and to collect emission light from a tissue sample of interest to two PMTs allowing either single excitation / single emission or ratiometric, dual excitation / single emission or single excitation / dual emission fluorescence detection of indicator dyes or natural fluorophores. The efficient transport of light from the excitation LEDs to the tissue sample, bleaching effects of the excitation light in both, polymer and fused silica-based fibers will be discussed. Furthermore, a new approach to maximize light collection of the emission light using high NA fibers and high NA coupling optics will be shown. Finally, first results on Ca2+ measurements in cardiac muscle slices in a traditional microscope setup and a horizontal tissue bath using fiber optic probes will be introduced and discussed.

  4. Age-related structural alterations in human skeletal muscle fibers and mitochondria are sex specific: relationship to single-fiber function.

    PubMed

    Callahan, Damien M; Bedrin, Nicholas G; Subramanian, Meenakumari; Berking, James; Ades, Philip A; Toth, Michael J; Miller, Mark S

    2014-06-15

    Age-related loss of skeletal muscle mass and function is implicated in the development of disease and physical disability. However, little is known about how age affects skeletal muscle structure at the cellular and ultrastructural levels or how such alterations impact function. Thus we examined skeletal muscle structure at the tissue, cellular, and myofibrillar levels in young (21-35 yr) and older (65-75 yr) male and female volunteers, matched for habitual physical activity level. Older adults had smaller whole muscle tissue cross-sectional areas (CSAs) and mass. At the cellular level, older adults had reduced CSAs in myosin heavy chain II (MHC II) fibers, with no differences in MHC I fibers. In MHC II fibers, older men tended to have fewer fibers with large CSAs, while older women showed reduced fiber size across the CSA range. Older adults showed a decrease in intermyofibrillar mitochondrial size; however, the age effect was driven primarily by women (i.e., age by sex interaction effect). Mitochondrial size was inversely and directly related to isometric tension and myosin-actin cross-bridge kinetics, respectively. Notably, there were no intermyofibrillar or subsarcolemmal mitochondrial fractional content or myofilament ultrastructural differences in the activity-matched young and older adults. Collectively, our results indicate age-related reductions in whole muscle size do not vary by sex. However, age-related structural alterations at the cellular and subcellular levels are different between the sexes and may contribute to different functional phenotypes in ways that modulate sex-specific reductions in physical capacity with age. Copyright © 2014 the American Physiological Society.

  5. Conversion of rat muscle fiber types. A time course study.

    PubMed

    Oakley, C R; Gollnick, P D

    1985-01-01

    Rats were used in this study to determine the time course of conversion of muscle fiber types. The right or left gastrocnemius muscle was removed thereby causing an overload on the ipsilateral soleus and plantaris muscles. The contralateral limb served as a control. The type II to type I fiber conversion was followed histochemically in the soleus and plantaris muscles for one to six weeks following surgery. Muscle sections were stained for myofibrillar actomyosin ATPase and NADH tetrazolium reductase. The type I population in the soleus muscle was 99.3% six weeks after synergist removal. The plantaris muscle underwent a two fold increase in the percentage of type I fibers after six weeks. Transitional fibers were prominent in the plantaris muscle and reached their peak at 4% (P less than 0.05) of the total population, four weeks after surgery.

  6. Muscle activity pattern dependent pain development and alleviation.

    PubMed

    Sjøgaard, Gisela; Søgaard, Karen

    2014-12-01

    Muscle activity is for decades considered to provide health benefits irrespectively of the muscle activity pattern performed and whether it is during e.g. sports, transportation, or occupational work tasks. Accordingly, the international recommendations for public health-promoting physical activity do not distinguish between occupational and leisure time physical activity. However, in this body of literature, attention has not been paid to the extensive documentation on occupational physical activity imposing a risk of impairment of health - in particular musculoskeletal health in terms of muscle pain. Focusing on muscle activity patterns and musculoskeletal health it is pertinent to elucidate the more specific aspects regarding exposure profiles and body regional pain. Static sustained muscle contraction for prolonged periods often occurs in the neck/shoulder area during occupational tasks and may underlie muscle pain development in spite of rather low relative muscle load. Causal mechanisms include a stereotype recruitment of low threshold motor units (activating type 1 muscle fibers) characterized by a lack of temporal as well as spatial variation in recruitment. In contrast during physical activities at leisure and sport the motor recruitment patterns are more dynamic including regularly relatively high muscle forces - also activating type 2 muscles fibers - as well as periods of full relaxation even of the type 1 muscle fibers. Such activity is unrelated to muscle pain development if adequate recovery is granted. However, delayed muscle soreness may develop following intensive eccentric muscle activity (e.g. down-hill skiing) with peak pain levels in thigh muscles 1-2 days after the exercise bout and a total recovery within 1 week. This acute pain profile is in contrast to the chronic muscle pain profile related to repetitive monotonous work tasks. The painful muscles show adverse functional, morphological, hormonal, as well as metabolic characteristics. Of

  7. Titin-based stiffening of muscle fibers in Ehlers-Danlos Syndrome

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ottenheijm, Coen A.C.; Voermans, Nicol C.; Hudson, Bryan D.

    Tenascin-X (TNX) is an extracellular matrix glycoprotein whose absence leads to Ehlers-Danlos Syndrome (EDS). TNX-deficient EDS patients present with joint hypermobility and muscle weakness attributable to increased compliance of the extracellular matrix. We hypothesized that in response to the increased compliance of the extracellular matrix in TNX-deficient EDS patients, intracellular adaptations take place in the elastic properties of the giant muscle protein titin. We performed extensive single muscle fiber mechanical studies to determine active and passive properties in TNX-deficient EDS patients. Gel-electrophoresis, Western blotting, and microarray studies were used to evaluate titin expression and phosphorylation. X-ray diffraction was used tomore » measure myofilament lattice spacing. Passive tension of muscle fibers from TNX-deficient EDS patients was markedly increased. Myofilament extraction experiments indicated that the increased passive tension is attributable to changes in the properties of the sarcomeric protein titin. Transcript and protein data indicated no changes in titin isoform expression. Instead, differences in posttranslational modifications within titin's elastic region were found. In patients, active tension was not different at maximal activation level, but at submaximal activation level it was augmented attributable to increased calcium sensitivity. This increased calcium sensitivity might be attributable to stiffer titin molecules. In response to the increased compliance of the extracellular matrix in muscle of TNX-deficient EDS patients, a marked intracellular stiffening occurs of the giant protein titin. The stiffening of titin partly compensates for the muscle weakness in these patients by augmenting submaximal active tension generation.« less

  8. Differences in muscle fiber size and associated energetic costs in phylogenetically paired tropical and temperate birds.

    PubMed

    Jimenez, Ana Gabriela; Williams, Joseph B

    2014-01-01

    Tropical and temperate birds provide a unique system to examine mechanistic consequences of life-history trade-offs at opposing ends of the pace-of-life spectrum; tropical birds tend to have a slow pace of life whereas temperate birds the opposite. Birds in the tropics have a lower whole-animal basal metabolic rate and peak metabolic rate, lower rates of reproduction, and longer survival than birds in temperate regions. Although skeletal muscle has a relatively low tissue-specific metabolism at rest, it makes up the largest fraction of body mass and therefore contributes more to basal metabolism than any other tissue. A principal property of muscle cells that influences their rate of metabolism is fiber size. The optimal fiber size hypothesis attempts to link whole-animal basal metabolic rate to the cost of maintaining muscle mass by stating that larger fibers may be metabolically cheaper to maintain since the surface area∶volume ratio (SA∶V) is reduced compared with smaller fibers and thus the amount of area to transport ions is also reduced. Because tropical birds have a reduced whole-organism metabolism, we hypothesized that they would have larger muscle fibers than temperate birds, given that larger muscle fibers have reduced energy demand from membrane Na(+)-K(+) pumps. Alternatively, smaller muscle fibers could result in a lower capacity for shivering and exercise. To test this idea, we examined muscle fiber size and Na(+)-K(+)-ATPase activity in 16 phylogenetically paired species of tropical and temperate birds. We found that 3 of the 16 paired comparisons indicated that tropical birds had significantly larger fibers, contrary to our hypothesis. Our data show that SA∶V is proportional to Na(+)-K(+)-ATPase activity in muscles of birds.

  9. Capsaicin and N-arachidonoyl-dopamine (NADA) decrease tension by activating both cannabinoid and vanilloid receptors in fast skeletal muscle fibers of the frog.

    PubMed

    Trujillo, Xóchitl; Ortiz-Mesina, Mónica; Uribe, Tannia; Castro, Elena; Montoya-Pérez, Rocío; Urzúa, Zorayda; Feria-Velasco, Alfredo; Huerta, Miguel

    2015-02-01

    Previous studies have indicated that vanilloid receptor (VR1) mRNA is expressed in muscle fibers. In this study, we evaluated the functional effects of VR1 activation. We measured caffeine-induced contractions in bundles of the extensor digitorum longus muscle of Rana pipiens. Isometric tension measurements showed that two VR1 agonists, capsaicin (CAP) and N-arachidonoyl-dopamine (NADA), reduced muscle peak tension to 57 ± 4 % and 71 ± 3% of control, respectively. The effect of CAP was partially blocked by a VR1 blocker, capsazepine (CPZ), but the effect of NADA was not changed by CPZ. Because NADA is able to act on cannabinoid receptors, which are also present in muscle fibers, we tested the cannabinoid antagonist AM281. We found that AM281 antagonized both CAP and NADA effects. AM281 alone reduced peak tension to 80 ± 6 % of control. With both antagonists, the CAP effect was completely blocked, and the NADA effect was partially blocked. These results provide pharmacological evidence of the functional presence of the VR1 receptor in fast skeletal muscle fibers of the frog and suggest that capsaicin and NADA reduce tension by activating both cannabinoid and vanilloid receptors.

  10. Repeatability of DTI-based skeletal muscle fiber tracking

    PubMed Central

    Heemskerk, Anneriet M.; Sinha, Tuhin K.; Wilson, Kevin J.; Ding, Zhaohua; Damon, Bruce M.

    2015-01-01

    Diffusion tensor imaging (DTI)-based muscle fiber tracking enables the measurement of muscle architectural parameters, such as pennation angle (θ) and fiber tract length (Lft), throughout the entire muscle. Little is known, however, about the repeatability of either the muscle architectural measures or the underlying diffusion measures. Therefore, the goal of this study was to investigate the repeatability of DTI fiber tracking-based measurements and θ and Lft. Four DTI acquisitions were performed on two days that allowed for between acquisition, within day, and between day analyses. The eigenvalues and fractional anisotropy were calculated at the maximum cross-sectional area of, and fiber tracking was performed in, the tibialis anterior muscle of nine healthy subjects. The between acquisitions condition had the highest repeatability for the DTI indices and the architectural parameters. The overall inter class correlation coefficients (ICC’s) were greater than 0.6 for both θ and Lft and the repeatability coefficients were θ <10.2° and Lft < 50 mm. In conclusion, under the experimental and data analysis conditions used, the repeatability of the diffusion measures is very good and repeatability of the architectural measurements is acceptable. Therefore, this study demonstrates the feasibility for longitudinal studies of alterations in muscle architecture using DTI-based fiber tracking, under similar noise conditions and with similar diffusion characteristics. PMID:20099372

  11. Contraction-induced injury to single permeabilized muscle fibers from normal and congenitally-clefted goat palates.

    PubMed

    Rader, Erik P; Cederna, Paul S; Weinzweig, Jeffrey; Panter, Kip E; Yu, Deborah; Buchman, Steven R; Larkin, Lisa M; Faulkner, John A

    2007-03-01

    Levator veli palatini muscles from normal palates of adult humans and goats are predominantly slow oxidative (type 1) fibers. However, 85% of levator veli palatini fibers from cleft palates of adult goats are physiologically fast (type 2). This fiber composition difference between cleft and normal palates may have implications in palatal function. For limb muscles, type 2 muscle fibers are more susceptible to lengthening contraction-induced injury than are type 1 fibers. We tested the hypothesis that, compared with single permeabilized levator veli palatini muscle fibers from normal palates of adult goats, those from cleft palates are more susceptible to lengthening contraction-induced injury. Congenital cleft palates were the result of chemically-induced decreased movement of the fetal head and tongue causing obstruction of palatal closure. Each muscle fiber was maximally activated and lengthened. Fiber type was determined by contractile properties and gel electrophoresis. Susceptibility to injury was assessed by measuring the decrease in maximum force following the lengthening contraction, expressed as a percentage of the initial force. Compared with fibers from normal palates that were all type 1 and had force deficits of 23 +/- 1%, fibers from cleft palates were all type 2 and sustained twofold greater deficits, 40 +/- 1% (p = .001). Levator veli palatini muscles from cleft palates of goats contain predominantly type 2 fibers that are highly susceptible to lengthening contraction-induced injury. This finding may have implications regarding palatal function and the incidence of velopharyngeal incompetence.

  12. Aging alters contractile properties and fiber morphology in pigeon skeletal muscle.

    PubMed

    Pistilli, Emidio E; Alway, Stephen E; Hollander, John M; Wimsatt, Jeffrey H

    2014-12-01

    In this study, we tested the hypothesis that skeletal muscle from pigeons would display age-related alterations in isometric force and contractile parameters as well as a shift of the single muscle fiber cross-sectional area (CSA) distribution toward smaller fiber sizes. Maximal force output, twitch contraction durations and the force-frequency relationship were determined in tensor propatagialis pars biceps muscle from young 3-year-old pigeons, middle-aged 18-year-old pigeons, and aged 30-year-old pigeons. The fiber CSA distribution was determined by planimetry from muscle sections stained with hematoxylin and eosin. Maximal force output of twitch and tetanic contractions was greatest in muscles from young pigeons, while the time to peak force of twitch contractions was longest in muscles from aged pigeons. There were no changes in the force-frequency relationship between the age groups. Interestingly, the fiber CSA distribution in aged muscles revealed a greater number of larger sized muscle fibers, which was verified visually in histological images. Middle-aged and aged muscles also displayed a greater amount of slow myosin containing muscle fibers. These data demonstrate that muscles from middle-aged and aged pigeons are susceptible to alterations in contractile properties that are consistent with aging, including lower force production and longer contraction durations. These functional changes were supported by the appearance of slow myosin containing muscle fibers in muscles from middle-aged and aged pigeons. Therefore, the pigeon may represent an appropriate animal model for the study of aging-related alterations in skeletal muscle function and structure.

  13. Motor unit and muscle fiber type grouping after peripheral nerve injury in the rat.

    PubMed

    Gordon, Tessa; de Zepetnek, Joanne E Totosy

    2016-11-01

    Muscle unit (MU) fibers innervated by one motoneuron and corresponding muscle fiber types are normally distributed in a mosaic. We asked whether, 4-8months after common peroneal nerve transection and random surgical alignment of nerve stumps in rat tibialis anterior muscles 1) reinnervated MU muscle and muscle fiber type clumping is invariant and 2) slow and fast motoneurons regenerate their nerve fibers within original endoneurial pathways. MU contractile forces were recorded in vivo, the MUs classified into types according to their contractile speed and fatigability, and one MU subjected to alternate exhaustive stimulation-recovery cycles to deplete glycogen for histochemical MU fiber recognition and enumeration, and muscle fiber typing. MU muscle fibers occupied defined territories whose size increased with MU force and muscle fiber numbers in normal and reinnervated muscles. The reinnervated MU muscle fiber territories were significantly smaller, the fibers clumped within 1-3 groups in 90% of the MUs, and each fiber lying adjacent to another significantly more frequently. Most reinnervated slow muscle fibers were normally located in the deep muscle compartment but substantial numbers were located abnormally in the superficial compartment. Our findings that well reinnervated muscle fibers clump in small muscles contrast with our earlier findings of clumping in large muscles only when reinnervated MU numbers were significantly reduced. We conclude that fiber type clumping is predictive of muscle reinnervation in small but not large muscles. In the latter muscles, clumping is more indicative of sprouting after partial nerve injuries than of muscle reinnervation after complete nerve injuries. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Eccentric contraction-induced injury to type I, IIa, and IIa/IIx muscle fibers of elderly adults

    USDA-ARS?s Scientific Manuscript database

    Muscles of old laboratory rodents experience exaggerated force losses after eccentric contractile activity. We extended this line of inquiry to humans and investigated the influence of fiber myosin heavy chain (MHC) isoform content on the injury process. Skinned muscle fiber segments, prepared from ...

  15. Myosin isoforms and contractile properties of single fibers of human Latissimus Dorsi muscle.

    PubMed

    Paoli, Antonio; Pacelli, Quirico F; Cancellara, Pasqua; Toniolo, Luana; Moro, Tatiana; Canato, Marta; Miotti, Danilo; Reggiani, Carlo

    2013-01-01

    The aim of our study was to investigate fiber type distribution and contractile characteristics of Latissimus Dorsi muscle (LDM). Samples were collected from 18 young healthy subjects (9 males and 9 females) through percutaneous fine needle muscle biopsy. The results showed a predominance of fast myosin heavy chain isoforms (MyHC) with 42% of MyHC 2A and 25% of MyHC 2X, while MyHC 1 represented only 33%. The unbalance toward fast isoforms was even greater in males (71%) than in females (64%). Fiber type distribution partially reflected MyHC isoform distribution with 28% type 1/slow fibers and 5% hybrid 1/2A fibers, while fast fibers were divided into 30% type 2A, 31% type A/X, 4% type X, and 2% type 1/2X. Type 1/slow fibers were not only less abundant but also smaller in cross-sectional area than fast fibers. During maximal isometric contraction, type 1/slow fibers developed force and tension significantly lower than the two major groups of fast fibers. In conclusion, the predominance of fast fibers and their greater size and strength compared to slow fibers reveal that LDM is a muscle specialized mainly in phasic and powerful activity. Importantly, such specialization is more pronounced in males than in females.

  16. Scaling of muscle architecture and fiber types in the rat hindlimb.

    PubMed

    Eng, Carolyn M; Smallwood, Laura H; Rainiero, Maria Pia; Lahey, Michele; Ward, Samuel R; Lieber, Richard L

    2008-07-01

    The functional capacity of a muscle is determined by its architecture and metabolic properties. Although extensive analyses of muscle architecture and fiber type have been completed in a large number of muscles in numerous species, there have been few studies that have looked at the interrelationship of these functional parameters among muscles of a single species. Nor have the architectural properties of individual muscles been compared across species to understand scaling. This study examined muscle architecture and fiber type in the rat (Rattus norvegicus) hindlimb to examine each muscle's functional specialization. Discriminant analysis demonstrated that architectural properties are a greater predictor of muscle function (as defined by primary joint action and anti-gravity or non anti-gravity role) than fiber type. Architectural properties were not strictly aligned with fiber type, but when muscles were grouped according to anti-gravity versus non-anti-gravity function there was evidence of functional specialization. Specifically, anti-gravity muscles had a larger percentage of slow fiber type and increased muscle physiological cross-sectional area. Incongruities between a muscle's architecture and fiber type may reflect the variability of functional requirements on single muscles, especially those that cross multiple joints. Additionally, discriminant analysis and scaling of architectural variables in the hindlimb across several mammalian species was used to explore whether any functional patterns could be elucidated within single muscles or across muscle groups. Several muscles deviated from previously described muscle architecture scaling rules and there was large variability within functional groups in how muscles should be scaled with body size. This implies that functional demands placed on muscles across species should be examined on the single muscle level.

  17. A novel optical imaging system for investigating sarcomere dynamics in single skeletal muscle fibers

    NASA Astrophysics Data System (ADS)

    Panchangam, Appaji; Witte, Russell S.; Claflin, Dennis R.; O'Donnell, Matthew; Faulkner, John A.

    2006-02-01

    The protein substructure of skeletal muscle fibers forms a diffraction grating with repeating units, termed 'sarcomeres'. A laser scanning system is described that maps the lengths of sarcomeres (SL) and the widths of the first-order diffraction lines (DLW) of permeabilized single fibers in real-time. The apparatus translates a laser beam (λ = 670 nm and w 0 = ~75 μm) along the length of a fiber segment through 20 contiguous regions per sweep at 500 sweeps/s. The fiber segments (~1 mm long) were obtained from vastus lateralis muscles of humans by needle biopsy. During both passive stretches and maximum fixed-end activations, the mappings of SL and DLW of the fibers were extracted from the diffraction spectra. Heterogeneity of SLs was evaluated by computing the standard deviation ( σ SL) of the 20 SLs measured during a single sweep. Compared with the σ SL before a passive stretch, the increase of 5+/-0.5% in σ SL after the passive stretch, indicated differences in passive length-tension relationships along the fiber. In contrast, no change, ~0.5+/-0.1%, was observed in DLW. Within 10s after the fiber was returned to its initial length, the shape of the SL profile returned close to pre-stretch conditions ( σ SL = 1+/- 0.2%). Following maximum Ca 2+ - activation of the fiber, the heterogeneity of the steady state SLs increased greatly (DLW up by ~300% and σ SL up by ~100%). The scanning system provided high resolution tracking of sarcomere behavior single muscle fibers. Potential applications are for studies of the mechanisms of muscle fiber injury and injury propagation.

  18. Functional, structural, and chemical changes in myosin associated with hydrogen peroxide treatment of skeletal muscle fibers.

    PubMed

    Prochniewicz, Ewa; Lowe, Dawn A; Spakowicz, Daniel J; Higgins, LeeAnn; O'Conor, Kate; Thompson, LaDora V; Ferrington, Deborah A; Thomas, David D

    2008-02-01

    To understand the molecular mechanism of oxidation-induced inhibition of muscle contractility, we have studied the effects of hydrogen peroxide on permeabilized rabbit psoas muscle fibers, focusing on changes in myosin purified from these fibers. Oxidation by 5 mM peroxide decreased fiber contractility (isometric force and shortening velocity) without significant changes in the enzymatic activity of myofibrils and isolated myosin. The inhibitory effects were reversed by treating fibers with dithiothreitol. Oxidation by 50 mM peroxide had a more pronounced and irreversible inhibitory effect on fiber contractility and also affected enzymatic activity of myofibrils, myosin, and actomyosin. Peroxide treatment also affected regulation of contractility, resulting in fiber activation in the absence of calcium. Electron paramagnetic resonance of spin-labeled myosin in muscle fibers showed that oxidation increased the fraction of myosin heads in the strong-binding structural state under relaxing conditions (low calcium) but had no effect under activating conditions (high calcium). This change in the distribution of structural states of myosin provides a plausible explanation for the observed changes in both contractile and regulatory functions. Mass spectroscopy analysis showed that 50 mM but not 5 mM peroxide induced oxidative modifications in both isoforms of the essential light chains and in the heavy chain of myosin subfragment 1 by targeting multiple methionine residues. We conclude that 1) inhibition of muscle fiber contractility via oxidation of myosin occurs at high but not low concentrations of peroxide and 2) the inhibitory effects of oxidation suggest a critical and previously unknown role of methionines in myosin function.

  19. Slow-Twitch Fiber Proportion in Skeletal Muscle Correlates With Insulin Responsiveness

    PubMed Central

    McCurry, Melanie P.; Marino, Anna; South, Mark A.; Howell, Mary E. A.; Layne, Andrew S.; Ramsey, Michael W.; Stone, Michael H.

    2013-01-01

    Context: The metabolic syndrome, characterized by central obesity with dyslipidemia, hypertension, and hyperglycemia, identifies people at high risk for type 2 diabetes. Objective: Our objective was to determine how the insulin resistance of the metabolic syndrome is related to muscle fiber composition. Design: Thirty-nine sedentary men and women (including 22 with the metabolic syndrome) had insulin responsiveness quantified using euglycemic clamps and underwent biopsies of the vastus lateralis muscle. Expression of insulin receptors, insulin receptor substrate-1, glucose transporter 4, and ATP synthase were quantified with immunoblots and immunohistochemistry. Participants and Setting: Participants were nondiabetic, metabolic syndrome volunteers and sedentary control subjects studied at an outpatient clinic. Main Outcome Measures: Insulin responsiveness during an insulin clamp and the fiber composition of a muscle biopsy specimen were evaluated. Results: There were fewer type I fibers and more mixed (type IIa) fibers in metabolic syndrome subjects. Insulin responsiveness and maximal oxygen uptake correlated with the proportion of type I fibers. Insulin receptor, insulin receptor substrate-1, and glucose transporter 4 expression were not different in whole muscle but all were significantly less in the type I fibers of metabolic syndrome subjects when adjusted for fiber proportion and fiber size. Fat oxidation and muscle mitochondrial expression were not different in the metabolic syndrome subjects. Conclusion: Lower proportion of type I fibers in metabolic syndrome muscle correlated with the severity of insulin resistance. Even though whole muscle content was normal, key elements of insulin action were consistently less in type I muscle fibers, suggesting their distribution was important in mediating insulin effects. PMID:23515448

  20. Prolyl hydroxylase domain 2 deficiency promotes skeletal muscle fiber-type transition via a calcineurin/NFATc1-dependent pathway.

    PubMed

    Shin, Junchul; Nunomiya, Aki; Kitajima, Yasuo; Dan, Takashi; Miyata, Toshio; Nagatomi, Ryoichi

    2016-01-01

    Hypoxia exposure is known to induce an alteration in skeletal muscle fiber-type distribution mediated by hypoxia-inducible factor (HIF)-α. The downstream pathway of HIF-α leading to fiber-type shift, however, has not been elucidated. The calcineurin pathway is one of the pathways responsible for slow muscle fiber transition. Because calcineurin pathway is activated by vascular endothelial growth factor (VEGF), one of the factors induced by HIF-1α, we hypothesized that the stabilization of HIF-1α may lead to slow muscle fiber transition via the activation of calcineurin pathway in skeletal muscles. To induce HIF-1α stabilization, we used a loss of function strategy to abrogate Prolyl hydroxylase domain protein (PHD) 2 responsible for HIF-1α hydroxylation making HIF-1α susceptible to ubiquitin dependent degradation by proteasome. The purpose of this study was therefore to examine the effect of HIF-1α stabilization in PHD2 conditional knockout mouse on skeletal muscle fiber-type transition and to elucidate the involvement of calcineurin pathway on muscle fiber-type transition. PHD2 deficiency resulted in an increased capillary density in skeletal muscles due to the induction of vascular endothelial growth factor. It also elicited an alteration of skeletal muscle phenotype toward the type I fibers in both of the soleus (35.8 % in the control mice vs. 46.7 % in the PHD2-deficient mice, p < 0.01) and the gastrocnemius muscle (0.94 vs. 1.89 %, p < 0.01), and the increased proportion of type I fibers appeared to correspond to the area of increased capillary density. In addition, calcineurin and nuclear factor of activated T cell (NFATc1) protein levels were increased in both the gastrocnemius and soleus muscles, suggesting that the calcineurin/NFATc1 pathway was responsible for the type I fiber transition regardless of PGC-1α, which responded minimally to PHD2 deficiency. Indeed, we found that tacrolimus (FK-506), a calcineurin inhibitor, successfully

  1. Limited fiber type grouping in self-reinnervation cat tibialis anterior muscles.

    PubMed

    Unguez, G A; Roy, R R; Bodine-Fowler, S; Edgerton, V R

    1996-10-01

    The percent and distribution patterns of three immunohistochemically identified fiber types within the anterior compartment of the cat tibialis anterior were determined 6 months after denervation and self-reinnervation. After self-reinnervation, mean frequencies of slow (9%) and fast (91%) fibers were similar to those in control (12% and 88%, respectively) muscles. However, a lower proportion of fast-1 (26%) and a higher proportion of fast-2 (65%) fibers were observed in self-reinnervated than control (32% and 56%) muscles. Quantitation of adjacencies between fibers of similar myosin heavy chain (MHC) phenotype, a measure of type grouping, revealed that the frequencies of two slow or two fast-1 fibers being adjacent in self-reinnervated muscles were similar to control. In contrast, the frequency of fast-2/fast-2 fiber adjacencies found in self-reinnervated muscles (45%) was significantly higher than in control muscles (37%). In both groups, the frequency of adjacencies between slow, fast-1, or fast-2 fibers was largely attributable to the number of each fiber type present. These data show that the incidence of grouping within each fiber type present was not altered after 6 months of self-reinnervation. Minimal changes in the spatial distribution of fiber types following self-reinnervation in adults suggests a limited degree of conversion of muscle fibers to a MHC phenotype matching the motoneuron characteristics.

  2. Skeletal Muscle Fatigability and Myosin Heavy Chain Fiber Type in Resistance Trained Men.

    PubMed

    Bagley, James R; McLeland, Kathryn A; Arevalo, Jose A; Brown, Lee E; Coburn, Jared W; Galpin, Andrew J

    2017-03-01

    Bagley, JR, McLeland, KA, Arevalo, JA, Brown, LE, Coburn, JW, and Galpin, AJ. Skeletal muscle fatigability and myosin heavy chain fiber type in resistance trained men. J Strength Cond Res 31(3): 602-607, 2017-Forty years ago, Thorstensson and Karlsson in 1976 described the link between muscle fatigability and fiber type, finding that more fast-twitch fibers were associated with a quicker onset of quadriceps fatigue. This provided the foundation for the Classic Thorstensson Test of fatigability and subsequent noninvasive fiber type prediction equation. This equation was developed with data from recreationally active (REC) men but has been implemented in participants with heterogeneous physical activity/exercise backgrounds. The accuracy of this approach in resistance trained (RET) men has not been established. Moreover, muscle fiber typing techniques have evolved considerably since this seminal work. Therefore, we reexamined this relationship using RET men and a more sensitive fiber typing method (single fiber myosin heavy chain [MHC] isoform classification). Fifteen RET men (age = 24.8 ± 1.3 years) performed maximal knee extensions (via isokinetic dynamometry) to determine peak torque (PT) and quadriceps fatigue percentage (FP) after 30 and 50 repetitions. Vastus lateralis (VL) single fiber MHC type was determined and fibers were grouped as %Fast (expressing MHC IIa, IIa/IIX, or IIx; no MHC I containing fibers). Resistance trained men exhibited 46% greater PT (RET = 207 ± 28 N·m vs. REC = 130 ± 8 N·m) and 28% more %Fast (RET = 61 ± 4% vs. REC = 44 ± 4%) than REC men. Additionally, RET men had a relatively homogeneous FP (64 ± 1%) ranging from 53 to 72%. No relationship was found between FP and MHC fiber type (R = 0.01, p > 0.05). The Classic Thorstensson Test may not accurately estimate VL fiber type composition in RET men, highlighting the (a) unique phenotypical/functional adaptations induced by chronic RET and (b) the need for more sensitive cellular

  3. Repeated blood flow restriction induces muscle fiber hypertrophy.

    PubMed

    Sudo, Mizuki; Ando, Soichi; Kano, Yutaka

    2017-02-01

    We recently developed an animal model to investigate the effects of eccentric contraction (ECC) and blood flow restriction (BFR) on muscle tissue at the cellular level. This study clarified the effects of repeated BFR, ECC, and BFR combined with ECC (BFR+ECC) on muscle fiber hypertrophy. Male Wistar rats were assigned to 3 groups: BFR, ECC, and BFR+ECC. The contralateral leg in the BFR group served as a control (CONT). Muscle fiber cross-sectional area (CSA) of the tibialis anterior was determined after the respective treatments for 6 weeks. CSA was greater in the BFR+ECC group than in the CONT (P < 0.01) and ECC (P < 0.05) groups. CSA was greater in the BFR group than that in the CONT group (P < 0.05). These results suggest that repeated BFR alone as well as BFR+ECC induces muscle fiber hypertrophy at the cellular level. Muscle Nerve 55: 274-276, 2017. © 2016 Wiley Periodicals, Inc.

  4. Magnitude of sarcomere extension correlates with initial sarcomere length during lengthening of activated single fibers from soleus muscle of rats.

    PubMed

    Panchangam, Appaji; Claflin, Dennis R; Palmer, Mark L; Faulkner, John A

    2008-08-01

    A laser-diffraction technique was developed that rapidly reports the lengths of sarcomeres (L(s)) in serially connected sectors of permeabilized single fibers. The apparatus translates a laser beam along the entire length of a fiber segment within 2 ms, with brief stops at each of 20 contiguous sectors. We tested the hypothesis that during lengthening contractions, when maximally activated fibers are stretched, sectors that contain the longer sarcomeres undergo greater increases in L(s) than those containing shorter sarcomeres. Fibers (n = 16) were obtained from the soleus muscles of adult male rats and the middle portions (length = 1.05 +/- 0.11 mm; mean +/- SD) were investigated. Single stretches of strain 27% and a strain rate of 54% s(-1) were initiated at maximum isometric stress and resulted in a 19 +/- 9% loss in isometric stress. The data on L(s) revealed that 1), the stretch was not distributed uniformly among the sectors, and 2), during the stretch, sectors at long L(s) before the stretch elongated more than those at short lengths. The findings support the hypothesis that during stretches of maximally activated skeletal muscles, sarcomeres at longer lengths are more susceptible to damage by excessive strain.

  5. Muscle fiber type proportion and size is not altered in mcardle disease.

    PubMed

    Henning, Franclo; Cunninghame, Carol Anne; Martín, Miguel Angel; Rubio, Juan Carlos; Arenas, Joaquín; Lucia, Alejandro; HernáNdez-Laín, Aurelio; Kohn, Tertius Abraham

    2017-06-01

    McArdle disease is a metabolic myopathy that presents with exercise intolerance and episodic rhabdomyolysis. Excessive muscle recruitment has also been shown to be present during strenuous exercise, suggesting decreased power output. These findings could potentially be explained by either impaired contractility, decreased fiber size, or altered fiber type proportion. However, there is a paucity of data on the morphological features seen on muscle histology. We examined muscle biopsies of patients with McArdle disease from a Spanish cohort and compared the findings with healthy controls. We found no significant difference in the fiber type proportion or mean fiber size between McArdle patients and controls in the biceps brachii or vastus lateralis muscles. No alterations in muscle fiber type proportion or size were found on muscle histology of patients with McArdle disease. Future research should focus on assessment of muscle fiber contractility to investigate the functional impairment. Muscle Nerve 55: 916-918, 2017. © 2016 Wiley Periodicals, Inc.

  6. Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism.

    PubMed

    Gan, Zhenji; Rumsey, John; Hazen, Bethany C; Lai, Ling; Leone, Teresa C; Vega, Rick B; Xie, Hui; Conley, Kevin E; Auwerx, Johan; Smith, Steven R; Olson, Eric N; Kralli, Anastasia; Kelly, Daniel P

    2013-06-01

    The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARβ/δ was shown to activate muscle endurance programs in transgenic mice. In contrast, muscle-specific transgenic overexpression of the related nuclear receptor, PPARα, results in reduced capacity for endurance exercise. We took advantage of the divergent actions of PPARβ/δ and PPARα to explore the downstream regulatory circuitry that orchestrates the programs linking muscle fiber type with energy metabolism. Our results indicate that, in addition to the well-established role in transcriptional control of muscle metabolic genes, PPARβ/δ and PPARα participate in programs that exert opposing actions upon the type I fiber program through a distinct muscle microRNA (miRNA) network, dependent on the actions of another nuclear receptor, estrogen-related receptor γ (ERRγ). Gain-of-function and loss-of-function strategies in mice, together with assessment of muscle biopsies from humans, demonstrated that type I muscle fiber proportion is increased via the stimulatory actions of ERRγ on the expression of miR-499 and miR-208b. This nuclear receptor/miRNA regulatory circuit shows promise for the identification of therapeutic targets aimed at maintaining muscle fitness in a variety of chronic disease states, such as obesity, skeletal myopathies, and heart failure.

  7. Intracellular calcium movements during excitation–contraction coupling in mammalian slow-twitch and fast-twitch muscle fibers

    PubMed Central

    Hollingworth, Stephen

    2012-01-01

    In skeletal muscle fibers, action potentials elicit contractions by releasing calcium ions (Ca2+) from the sarcoplasmic reticulum. Experiments on individual mouse muscle fibers micro-injected with a rapidly responding fluorescent Ca2+ indicator dye reveal that the amount of Ca2+ released is three- to fourfold larger in fast-twitch fibers than in slow-twitch fibers, and the proportion of the released Ca2+ that binds to troponin to activate contraction is substantially smaller. PMID:22450485

  8. Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

    PubMed

    Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

    2017-03-01

    The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth. © 2017 Federation of European Biochemical Societies.

  9. Fiber transformation and replacement in low-frequency stimulated rabbit fast-twitch muscles.

    PubMed

    Schuler, M; Pette, D

    1996-08-01

    The fast-to-slow conversion of rabbit skeletal muscles by chronic low-frequency (10 Hz, 12 h daily) stimulation involves (1) sequential fast-to-slow fiber-type transitions in the order of type IID-->type IIA-->type I, and (2) the replacement of deteriorating fast-twitch glycolytic fibers by new fibers derived from satellite cells and myotubes. These two processes were analyzed in 30- and 60-day stimulated extensor digitorum longus and tibialis anterior muscles. Fast-to-slow transforming fibers were identified by myofibrillar actomyosin histochemistry as type C fibers and immunohistochemically by their reaction with monoclonal antibodies specific to slow and fast myosin heavy chain isoforms. In situ hybridization of mRNA specific to the myosin heavy chain I isoform identified all fibers expressing slow myosin, i.e., type I and C fibers. The fraction of transforming fibers ranged between 35% and 50% in 30-day stimulated muscles. The percentage of type I fibers (20%) was threefold elevated in extensor digitorum longus muscle, but unaltered (3.5%) in tibialis anterior muscle, suggesting that fast-to-slow fiber conversion was more advanced in the former than in the latter. Fiber replacement was indicated by the finding that the fiber populations of both muscles contained 15% myotubes or small fibers with central nuclei. In situ hybridization revealed that myotubes and small regenerating fibers uniformly expressed myosin heavy chain I mRNA. Similarly, high percentages of slow-myosin-expressing myotubes and small fibers were found in 60-day stimulated muscles.

  10. Fiber specific changes in sphingolipid metabolism in skeletal muscles of hyperthyroid rats.

    PubMed

    Chabowski, A; Zendzian-Piotrowska, M; Mikłosz, A; Łukaszuk, B; Kurek, K; Górski, J

    2013-07-01

    Thyroid hormones (T3, T4) are well known modulators of different cellular signals including the sphingomyelin pathway. However, studies regarding downstream effects of T3 on sphingolipid metabolism in skeletal muscle are scarce. In the present work we sought to investigate the effects of hyperthyroidism on the activity of the key enzymes of ceramide metabolism as well as the content of fundamental sphingolipids. Based on fiber/metabolic differences, we chose three different skeletal muscles, with diverse fiber compositions: soleus (slow-twitch oxidative), red (fast-twitch oxidative-glycolytic) and white (fast-twitch glycolytic) section of gastrocnemius. We demonstrated that T3 induced accumulation of sphinganine, ceramide, sphingosine, as well as sphingomyelin, mostly in soleus and in red, but not white section of gastrocnemius. Concomitantly, the activity of serine palmitoyltransferase and acid/neutral ceramidase was increased in more oxidative muscles. In conclusion, hyperthyroidism induced fiber specific changes in the content of sphingolipids that were relatively more related to de novo synthesis of ceramide rather than to its generation via hydrolysis of sphingomyelin.

  11. Fnip1 regulates skeletal muscle fiber type specification, fatigue resistance, and susceptibility to muscular dystrophy

    PubMed Central

    Reyes, Nicholas L.; Banks, Glen B.; Tsang, Mark; Margineantu, Daciana; Gu, Haiwei; Djukovic, Danijel; Chan, Jacky; Torres, Michelle; Liggitt, H. Denny; Hirenallur-S, Dinesh K.; Hockenbery, David M.; Raftery, Daniel; Iritani, Brian M.

    2015-01-01

    Mammalian skeletal muscle is broadly characterized by the presence of two distinct categories of muscle fibers called type I “red” slow twitch and type II “white” fast twitch, which display marked differences in contraction strength, metabolic strategies, and susceptibility to fatigue. The relative representation of each fiber type can have major influences on susceptibility to obesity, diabetes, and muscular dystrophies. However, the molecular factors controlling fiber type specification remain incompletely defined. In this study, we describe the control of fiber type specification and susceptibility to metabolic disease by folliculin interacting protein-1 (Fnip1). Using Fnip1 null mice, we found that loss of Fnip1 increased the representation of type I fibers characterized by increased myoglobin, slow twitch markers [myosin heavy chain 7 (MyH7), succinate dehydrogenase, troponin I 1, troponin C1, troponin T1], capillary density, and mitochondria number. Cultured Fnip1-null muscle fibers had higher oxidative capacity, and isolated Fnip1-null skeletal muscles were more resistant to postcontraction fatigue relative to WT skeletal muscles. Biochemical analyses revealed increased activation of the metabolic sensor AMP kinase (AMPK), and increased expression of the AMPK-target and transcriptional coactivator PGC1α in Fnip1 null skeletal muscle. Genetic disruption of PGC1α rescued normal levels of type I fiber markers MyH7 and myoglobin in Fnip1-null mice. Remarkably, loss of Fnip1 profoundly mitigated muscle damage in a murine model of Duchenne muscular dystrophy. These results indicate that Fnip1 controls skeletal muscle fiber type specification and warrant further study to determine whether inhibition of Fnip1 has therapeutic potential in muscular dystrophy diseases. PMID:25548157

  12. Tension in Skinned Frog Muscle Fibers in Solutions of Varying Ionic Strength and Neutral Salt Composition

    PubMed Central

    Gordon, A. M.; Godt, R. E.; Donaldson, S. K. B.; Harris, C. E.

    1973-01-01

    The maximal calcium-activated isometric tension produced by a skinned frog single muscle fiber falls off as the ionic strength of the solution bathing this fiber is elevated declining to zero near 0.5 M as the ionic strength is varied using KCl. When other neutral salts are used, the tension always declines at high ionic strength, but there is some difference between the various neutral salts used. The anions and cations can be ordered in terms of their ability to inhibit the maximal calcium-activated tension. The order of increasing inhibition of tension (decreasing tension) at high ionic strength for anions is propionate- ≃ SO4 -- < Cl- < Br-. The order of increasing inhibition of calcium-activated tension for cations is K+ ≃ Na+ ≃ TMA+ < TEA+ < TPrA+ < TBuA+. The decline of maximal calcium-activated isometric tension with elevated salt concentration (ionic strength) can quantitatively explain the decline of isometric tetanic tension of a frog muscle fiber bathed in a hypertonic solution if one assumes that the internal ionic strength of a muscle fiber in normal Ringer's solution is 0.14–0.17 M. There is an increase in the base-line tension of a skinned muscle fiber bathed in a relaxing solution (no added calcium and 3 mM EGTA) of low ionic strength. This tension, which has no correlate in the intact fiber in hypotonic solutions, appears to be a noncalcium-activated tension and correlates more with a declining ionic strength than with small changes in [MgATP], [Mg], pH buffer, or [EGTA]. It is dependent upon the specific neutral salts used with cations being ordered in increasing inhibition of this noncalcium-activated tension (decreasing tension) as TPrA+ < TMA+ < K+ ≃ Na+. Measurements of potentials inside these skinned muscle fibers bathed in relaxing solutions produced occasional small positive values (<6 mV) which were not significantly different from zero. PMID:4543066

  13. Novel single skeletal muscle fiber analysis reveals a fiber type-selective effect of acute exercise on glucose uptake.

    PubMed

    Cartee, Gregory D; Arias, Edward B; Yu, Carmen S; Pataky, Mark W

    2016-11-01

    One exercise session can induce subsequently elevated insulin sensitivity that is largely attributable to greater insulin-stimulated glucose uptake by skeletal muscle. Because skeletal muscle is a heterogeneous tissue comprised of diverse fiber types, our primary aim was to determine exercise effects on insulin-independent and insulin-dependent glucose uptake by single fibers of different fiber types. We hypothesized that each fiber type featuring elevated insulin-independent glucose uptake immediately postexercise (IPEX) would be characterized by increased insulin-dependent glucose uptake at 3.5 h postexercise (3.5hPEX). Rat epitrochlearis muscles were isolated and incubated with 2-[ 3 H]deoxyglucose. Muscles from IPEX and sedentary (SED) controls were incubated without insulin. Muscles from 3.5hPEX and SED controls were incubated ± insulin. Glucose uptake (2-[ 3 H]deoxyglucose accumulation) and fiber type (myosin heavy chain isoform expression) were determined for single fibers dissected from the muscles. Major new findings included the following: 1) insulin-independent glucose uptake was increased IPEX in single fibers of each fiber type (types I, IIA, IIB, IIBX, and IIX), 2) glucose uptake values from insulin-stimulated type I and IIA fibers exceeded the values for the other fiber types, 3) insulin-stimulated glucose uptake for type IIX exceeded IIB fibers, and 4) the 3.5hPEX group vs. SED had greater insulin-stimulated glucose uptake in type I, IIA, IIB, and IIBX but not type IIX fibers. Insulin-dependent glucose uptake was increased at 3.5hPEX in each fiber type except for IIX fibers, although insulin-independent glucose uptake was increased IPEX in all fiber types (including type IIX). Single fiber analysis enabled the discovery of this fiber type-related difference for postexercise, insulin-stimulated glucose uptake. Copyright © 2016 the American Physiological Society.

  14. Acetylcholinesterase activity in soleus muscle intrafusal and extrafusal fibres in tail suspended rats.

    PubMed

    Tang, Bin; Fan, Xiao-li; Wu, Su-di

    2002-10-01

    Objective. To explore the mechanisms involved in muscle atrophy and conversion of the fiber types induced by simulated weightlessness. Method. Weightlessness was simulated by tail suspension of female rats. Intrafusal and extrafusal fibers of soleus muscles in the rat were examined histochemically for their activity of acetylcholinesterase (AChE) and succinic dehydrogenase (SDH) in 7 d, 14 d, 21 d tail-suspended groups and control groups. Result. Staining for succinic dehydrogenase showed that simulated weightlessness caused obvious atrophy and change in fiber type composition in soleus muscle, with decrease of the proportion of type I fiber and increase of type II fiber. Acetylcholinesterase activities of intrafusal and extrafusal fibers were both decreased significantly after 21 d tail suspension. Conclusion. Simulated weightlessness could induce decrease of AChE activity in neuromuscular junctions, which might be linked with decrease in motor neuron activity.

  15. Enhancement of force generated by individual myosin heads in skinned rabbit psoas muscle fibers at low ionic strength.

    PubMed

    Sugi, Haruo; Abe, Takahiro; Kobayashi, Takakazu; Chaen, Shigeru; Ohnuki, Yoshiki; Saeki, Yasutake; Sugiura, Seiryo

    2013-01-01

    Although evidence has been presented that, at low ionic strength, myosin heads in relaxed skeletal muscle fibers form linkages with actin filaments, the effect of low ionic strength on contraction characteristics of Ca(2+)-activated muscle fibers has not yet been studied in detail. To give information about the mechanism of muscle contraction, we have examined the effect of low ionic strength on the mechanical properties and the contraction characteristics of skinned rabbit psoas muscle fibers in both relaxed and maximally Ca(2+)-activated states. By progressively decreasing KCl concentration from 125 mM to 0 mM (corresponding to a decrease in ionic strength μ from 170 mM to 50 mM), relaxed fibers showed changes in mechanical response to sinusoidal length changes and ramp stretches, which are consistent with the idea of actin-myosin linkage formation at low ionic strength. In maximally Ca(2+)-activated fibers, on the other hand, the maximum isometric force increased about twofold by reducing KCl concentration from 125 to 0 mM. Unexpectedly, determination of the force-velocity curves indicated that, the maximum unloaded shortening velocity Vmax, remained unchanged at low ionic strength. This finding indicates that the actin-myosin linkages, which has been detected in relaxed fibers at low ionic strength, are broken quickly on Ca(2+) activation, so that the linkages in relaxed fibers no longer provide any internal resistance against fiber shortening. The force-velocity curves, obtained at various levels of steady Ca(2+)-activated isometric force, were found to be identical if they are normalized with respect to the maximum isometric force. The MgATPase activity of muscle fibers during isometric force generation was found not to change appreciably at low ionic strength despite the two-fold increase in Ca(2+)-activated isometric force. These results can be explained in terms of enhancement of force generated by individual myosin heads, but not by any changes in

  16. Enhancement of Force Generated by Individual Myosin Heads in Skinned Rabbit Psoas Muscle Fibers at Low Ionic Strength

    PubMed Central

    Sugi, Haruo; Abe, Takahiro; Kobayashi, Takakazu; Chaen, Shigeru; Ohnuki, Yoshiki; Saeki, Yasutake; Sugiura, Seiryo

    2013-01-01

    Although evidence has been presented that, at low ionic strength, myosin heads in relaxed skeletal muscle fibers form linkages with actin filaments, the effect of low ionic strength on contraction characteristics of Ca2+-activated muscle fibers has not yet been studied in detail. To give information about the mechanism of muscle contraction, we have examined the effect of low ionic strength on the mechanical properties and the contraction characteristics of skinned rabbit psoas muscle fibers in both relaxed and maximally Ca2+-activated states. By progressively decreasing KCl concentration from 125 mM to 0 mM (corresponding to a decrease in ionic strength μ from 170 mM to 50 mM), relaxed fibers showed changes in mechanical response to sinusoidal length changes and ramp stretches, which are consistent with the idea of actin-myosin linkage formation at low ionic strength. In maximally Ca2+-activated fibers, on the other hand, the maximum isometric force increased about twofold by reducing KCl concentration from 125 to 0 mM. Unexpectedly, determination of the force-velocity curves indicated that, the maximum unloaded shortening velocity Vmax, remained unchanged at low ionic strength. This finding indicates that the actin-myosin linkages, which has been detected in relaxed fibers at low ionic strength, are broken quickly on Ca2+ activation, so that the linkages in relaxed fibers no longer provide any internal resistance against fiber shortening. The force-velocity curves, obtained at various levels of steady Ca2+-activated isometric force, were found to be identical if they are normalized with respect to the maximum isometric force. The MgATPase activity of muscle fibers during isometric force generation was found not to change appreciably at low ionic strength despite the two-fold increase in Ca2+-activated isometric force. These results can be explained in terms of enhancement of force generated by individual myosin heads, but not by any changes in kinetic properties

  17. Fat content in individual muscle fibers of lean and obese subjects.

    PubMed

    Malenfant, P; Joanisse, D R; Thériault, R; Goodpaster, B H; Kelley, D E; Simoneau, J A

    2001-09-01

    To examine skeletal muscle intracellular triglyceride concentration in different fiber types in relation to obesity. Skeletal muscle fiber type distribution and intracellular lipid content were measured in vastus lateralis samples obtained by needle biopsy from lean and obese individuals. Seven lean controls (body mass index (BMI) 23.0+/-3.3 kg/m(2); mean+/-s.d.) and 14 obese (BMI 33.7+/-2.7 kg/m(2)) individuals; both groups included comparable proportions of men and women. Samples were histochemically stained for the identification of muscle fiber types (myosin ATPase) and intracellular lipid aggregates (oil red O dye). The number and size of fat aggregates as well as their concentration within type I, IIA and IIB muscle fiber types were measured. The cellular distribution of the lipid aggregates was also examined. The size of fat aggregates was not affected by obesity but the number of lipid droplets within muscle fibers was twice as abundant in obese compared to lean individuals. This was seen in type I (298+/-135 vs 129+/-75; obese vs lean, P<0.05), IIA (132+/-67 vs 79+/-29; P<0.05), and IIB (103+/-63 vs 51+/-13; P<0.05) muscle fibers. A more central distribution of lipid droplets was observed in muscle fibers of obese compared to lean subjects (27.2+/-5.7 vs 19.7+/-6.4%; P<0.05). The higher number of lipid aggregates and the disposition to a greater central distribution in all fiber types in obesity indicate important changes in lipid metabolism and/or storage that are fiber type-independent.

  18. Functional imaging of skeletal muscle fiber in different physiological states by second harmonic generation

    NASA Astrophysics Data System (ADS)

    Nucciotti, V.; Stringari, C.; Sacconi, L.; Vanzi, F.; Tesi, C.; Piroddi, N.; Poggesi, C.; Castiglioni, C.; Milani, A.; Linari, M.; Piazzesi, G.; Lombardi, V.; Pavone, F. S.

    2007-07-01

    The intrinsically ordered arrays of proteins in skeletal muscle allows imaging of this tissue by Second Harmonic Generation (SHG). Biochemical and colocalization studies have gathered an increasing wealth of clues for the attribution of the molecular origin of the muscle SHG signal to the motor protein myosin. Thus, SHG represents a potentially very powerful tool in the investigation of structural dynamics occurring in muscle during active production of force. A full characterization of the polarization-dependence of the SHG signal represents a very selective information on the orientation of the emitting proteins and their dynamics during contraction, provided that different physiological states of muscle (relaxed, rigor and active) exhibit distinct patterns of SHG polarization dependence. Here polarization data are obtained from single frog muscle fibers at rest and during isometric contraction and interpreted, by means of a model, in terms of an average orientation of the SHG emitters which are structured with a cylindrical symmetry about the fiber axis. Optimizing the setup for accurate polarization measurements with SHG, we developed a line scan imaging method allowing measurement of SHG polarization curves in different physiological states. We demonstrate that muscle fiber displays a measurable variation of the orientation of SHG emitters with the transition from rest to isometric contraction.

  19. Pharmacological activation of PPARbeta/delta stimulates utrophin A expression in skeletal muscle fibers and restores sarcolemmal integrity in mature mdx mice.

    PubMed

    Miura, Pedro; Chakkalakal, Joe V; Boudreault, Louise; Bélanger, Guy; Hébert, Richard L; Renaud, Jean-Marc; Jasmin, Bernard J

    2009-12-01

    A therapeutic strategy to treat Duchenne muscular dystrophy (DMD) involves identifying compounds that can elevate utrophin A expression in muscle fibers of affected patients. The dystrophin homologue utrophin A can functionally substitute for dystrophin when its levels are enhanced in the mdx mouse model of DMD. Utrophin A expression in skeletal muscle is regulated by mechanisms that promote the slow myofiber program. Since activation of peroxisome proliferator-activated receptor (PPAR) beta/delta promotes the slow oxidative phenotype in skeletal muscle, we initiated studies to determine whether pharmacological activation of PPARbeta/delta provides functional benefits to the mdx mouse. GW501516, a PPARbeta/delta agonist, was found to stimulate utrophin A mRNA levels in C2C12 muscle cells through an element in the utrophin A promoter. Expression of PPARbeta/delta was greater in skeletal muscles of mdx versus wild-type mice. We treated 5-7-week-old mdx mice with GW501516 for 4 weeks. This treatment increased the percentage of muscle fibers expressing slower myosin heavy chain isoforms and stimulated utrophin A mRNA levels leading to its increased expression at the sarcolemma. Expression of alpha1-syntrophin and beta-dystroglycan was restored to the sarcolemma. Improvement of mdx sarcolemmal integrity was evidenced by decreased intracellular IgM staining and decreased in vivo Evans blue dye (EBD) uptake. GW501516 treatment also conferred protection against eccentric contraction (ECC)-induced damage of mdx skeletal muscles, as shown by a decreased contraction-induced force drop and reduction of dye uptake during ECC. These results demonstrate that pharmacological activation of PPARbeta/delta might provide functional benefits to DMD patients through enhancement of utrophin A expression.

  20. Experimental comparisons between McKibben type artificial muscles and straight fibers type artificial muscles

    NASA Astrophysics Data System (ADS)

    Nakamura, Taro

    2007-01-01

    This paper describes experimental comparison between a conventional McKibben type artificial muscle and a straight fibers type artificial muscle developed by the authors. A wearable device and a rehabilitation robot which assists a human muscle should have characteristics similar to those of human muscle. In addition, because the wearable device and the rehabilitation robot should be light, an actuator with a high power/weight ratio is needed. At present, the McKibben type is widely used as an artificial muscle, but in fact its physical model is highly nonlinear. Further, the heat and mechanical loss of this actuator are large because of the friction caused by the expansion and contraction of the sleeve. Therefore, the authors have developed an artificial muscle tube in which high strength glass fibers have been built into the tube made from natural latex rubber. As results, experimental results demonstrated that the developed artificial muscle is more effective regarding its fundamental characteristics than that of the McKibben type; the straight fibers types of artificial muscle have more contraction ratio and power, longer lifetime than the McKibben types. And it has almost same characteristics of human muscle for isotonic and isometric that evaluate it dynamically.

  1. AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration*

    PubMed Central

    Fu, Xing; Zhu, Mei-Jun; Dodson, Mike V.; Du, Min

    2015-01-01

    Satellite cells are the major myogenic stem cells residing inside skeletal muscle and are indispensable for muscle regeneration. Satellite cells remain largely quiescent but are rapidly activated in response to muscle injury, and the derived myogenic cells then fuse to repair damaged muscle fibers or form new muscle fibers. However, mechanisms eliciting metabolic activation, an inseparable step for satellite cell activation following muscle injury, have not been defined. We found that a noncanonical Sonic Hedgehog (Shh) pathway is rapidly activated in response to muscle injury, which activates AMPK and induces a Warburg-like glycolysis in satellite cells. AMPKα1 is the dominant AMPKα isoform expressed in satellite cells, and AMPKα1 deficiency in satellite cells impairs their activation and myogenic differentiation during muscle regeneration. Drugs activating noncanonical Shh promote proliferation of satellite cells, which is abolished because of satellite cell-specific AMPKα1 knock-out. Taken together, AMPKα1 is a critical mediator linking noncanonical Shh pathway to Warburg-like glycolysis in satellite cells, which is required for satellite activation and muscle regeneration. PMID:26370082

  2. Effects of Streptomycin Administration on Increases in Skeletal Muscle Fiber Permeability and Size Following Eccentric Muscle Contractions.

    PubMed

    Hayao, Keishi; Tamaki, Hiroyuki; Nakagawa, Kouki; Tamakoshi, Keigo; Takahashi, Hideaki; Yotani, Kengo; Ogita, Futoshi; Yamamoto, Noriaki; Onishi, Hideaki

    2018-06-01

    The purpose of this study was to investigate the preventive effect of streptomycin (Str) administration on changes in membrane permeability and the histomorphological characteristics of damaged muscle fibers following eccentric contraction (ECC ). Eighteen 7-week-old male Fischer 344 rats were randomly assigned to three groups: control (Cont), ECC, and ECC with Str (ECC + Str). The tibialis anterior (TA) muscles in both ECC groups were stimulated electrically and exhibited ECC. Evans blue dye (EBD), a marker of muscle fiber damage associated with increased membrane permeability, was injected 24 hr before TA muscle sampling. The number of EBD-positive fibers, muscle fiber cross-sectional area (CSA), and roundness were determined via histomorphological analysis. The ECC intervention resulted in an increased fraction of EBD-positive fibers, a larger CSA, and decreased roundness. The fraction of EBD-positive fibers was 79% lower in the ECC + Str group than in the ECC group. However, there was no difference in the CSA and roundness of the EBD-positive fibers between the two ECC groups. These results suggest that Str administration can reduce the number of myofibers that increase membrane permeability following ECC, but does not ameliorate the extent of fiber swelling in extant EBD-positive fibers. Anat Rec, 301:1096-1102, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  3. Differential Expression of NADPH Oxidases Depends on Skeletal Muscle Fiber Type in Rats.

    PubMed

    Loureiro, Adriano César Carneiro; do Rêgo-Monteiro, Igor Coutinho; Louzada, Ruy A; Ortenzi, Victor Hugo; de Aguiar, Angélica Ponte; de Abreu, Ewerton Sousa; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Hecht, Fabio; de Oliveira, Ariclécio Cunha; Ceccatto, Vânia Marilande; Fortunato, Rodrigo S; Carvalho, Denise P

    2016-01-01

    NADPH oxidases (NOX) are important sources of reactive oxygen species (ROS) in skeletal muscle, being involved in excitation-contraction coupling. Thus, we aimed to investigate if NOX activity and expression in skeletal muscle are fiber type specific and the possible contribution of this difference to cellular oxidative stress. Oxygen consumption rate, NOX activity and mRNA levels, and the activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD), as well as the reactive protein thiol levels, were measured in the soleus (SOL), red gastrocnemius (RG), and white gastrocnemius (WG) muscles of rats. RG showed higher oxygen consumption flow than SOL and WG, while SOL had higher oxygen consumption than WG. SOL showed higher NOX activity, as well as NOX2 and NOX4 mRNA levels, antioxidant enzymatic activities, and reactive protein thiol contents when compared to WG and RG. NOX activity and NOX4 mRNA levels as well as antioxidant enzymatic activities were higher in RG than in WG. Physical exercise increased NOX activity in SOL and RG, specifically NOX2 mRNA levels in RG and NOX4 mRNA levels in SOL. In conclusion, we demonstrated that NOX activity and expression differ according to the skeletal muscle fiber type, as well as antioxidant defense.

  4. Muscle enzyme and fiber type-specific sarcomere protein increases in serum after inertial concentric-eccentric exercise.

    PubMed

    Carmona, G; Guerrero, M; Cussó, R; Padullés, J M; Moras, G; Lloret, M; Bedini, J L; Cadefau, J A

    2015-12-01

    Muscle damage induced by inertial exercise performed on a flywheel device was assessed through the serum evolution of muscle enzymes, interleukin 6, and fiber type-specific sarcomere proteins such as fast myosin (FM) and slow myosin (SM). We hypothesized that a model of muscle damage could be constructed by measuring the evolution of serum concentration of muscle proteins following inertial exercise, according to their molecular weight and the fiber compartment in which they are located. Moreover, by measuring FM and SM, the type of fibers that are affected could be assessed. Serum profiles were registered before and 24, 48, and 144 h after exercise in 10 healthy and recreationally active young men. Creatine kinase (CK) and CK-myocardial band isoenzyme increased in serum early (24 h) and returned to baseline values after 48 h. FM increased in serum late (48 h) and remained elevated 144 h post-exercise. The increase in serum muscle enzymes suggests increased membrane permeability of both fast and slow fibers, and the increase in FM reveals sarcomere disruption as well as increased membrane permeability of fast fibers. Consequently, FM could be adopted as a fiber type-specific biomarker of muscle damage. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Fiber size, type, and myosin heavy chain content in rhesus hindlimb muscles after 2 weeks at 2 G

    NASA Technical Reports Server (NTRS)

    Tavakol, Morteza; Roy, Roland R.; Kim, Jung A.; Zhong, Hui; Hodgson, John A.; Hoban-Higgins, Tana M.; Fuller, Charles A.; Edgerton, V. Reggie

    2002-01-01

    BACKGROUND: Fiber atrophy and an increase in the percentage of fast fibers have been observed in Rhesus leg muscles after spaceflight. Hypothesis: Hypergravity will result in muscle fiber hypertrophy and an increase in the percentage of slow fibers. METHODS: Open muscle biopsies were obtained from Rhesus soleus, medial gastrocnemius (MG), and tibialis anterior (TA) muscles before and after 14 d of centrifugation (2 G) and in time-matched controls. Cage activity levels were measured by telemetry. RESULTS: Based on monoclonal antibody binding for myosin heavy chains (MHC), the fastest region of soleus contained a higher proportion of type I+II (27 vs. 13%) and had a tendency for a lower proportion of type I (38 vs. 61%, p = 0.10) fibers after than before centrifugation. There was a higher proportion of type I+II fibers in post- vs. pre-2 G (10 vs. 0.6%) MG biopsies. Fiber type distribution and MHC composition were unaffected in the TA. Overall, mean fiber sizes were unaffected by centrifugation. Average cage activity levels were 36% lower during than before 2 G. CONCLUSIONS: Our hypothesis was rejected. The changes in the proportion of fibers expressing type I MHC are the reverse of that expected with chronic loading of extensors and, paradoxically, are similar to changes observed with chronic unloading, such as occurs during spaceflight, in this primate model. The data are consistent with the observed decrease in total daily activity levels.

  6. Satellite cell depletion prevents fiber hypertrophy in skeletal muscle.

    PubMed

    Egner, Ingrid M; Bruusgaard, Jo C; Gundersen, Kristian

    2016-08-15

    The largest mammalian cells are the muscle fibers, and they have multiple nuclei to support their large cytoplasmic volumes. During hypertrophic growth, new myonuclei are recruited from satellite stem cells into the fiber syncytia, but it was recently suggested that such recruitment is not obligatory: overload hypertrophy after synergist ablation of the plantaris muscle appeared normal in transgenic mice in which most of the satellite cells were abolished. When we essentially repeated these experiments analyzing the muscles by immunohistochemistry and in vivo and ex vivo imaging, we found that overload hypertrophy was prevented in the satellite cell-deficient mice, in both the plantaris and the extensor digitorum longus muscles. We attribute the previous findings to a reliance on muscle mass as a proxy for fiber hypertrophy, and to the inclusion of a significant number of regenerating fibers in the analysis. We discuss that there is currently no model in which functional, sustainable hypertrophy has been unequivocally demonstrated in the absence of satellite cells; an exception is re-growth, which can occur using previously recruited myonuclei without addition of new myonuclei. © 2016. Published by The Company of Biologists Ltd.

  7. Fiber types of the anterior and lateral cervical muscles in elderly males.

    PubMed

    Cornwall, Jon; Kennedy, Ewan

    2015-09-01

    The anterior and lateral cervical muscles (ALCM) are generally considered to be postural, yet few studies have investigated ALCM fiber types to help clarify the function of these muscles. This study aimed to systematically investigate ALCM fiber types in cadavers. Anterior and lateral cervical muscles (four scalenus anterior, medius, posterior muscles; five longus colli, five longus capitis taken bilaterally from one cadaver) were removed from four male embalmed cadavers (mean age 87.25 years). Paraffin-embedded specimens were sectioned then stained immunohistochemically to identify type I and II skeletal muscle fibers. Proportional fiber type numbers and cross-sectional area (CSA) occupied by fiber types were determined using stereology (random systematic sampling). Results were analyzed using ANOVA (P < 0.05) and descriptive statistics. Scalenus anterior had the greatest average number and CSA of type I fibers (71.9 and 83.7%, respectively); longus capitis had the lowest number (48.5%) and CSA (61.4%). All scalene muscles had significantly greater type I CSA than longus capitis and longus colli; scalenus anterior and medius had significantly greater type I numbers than longus capitis and longus colli. Some significant differences were observed between individual cadavers in longus colli for CSA, and longus capitis for number. The ALCM do not share a common functional fiber type distribution, although similar fiber type distributions are shared by longus colli and longus capitis, and by the scalene muscles. Contrary to conventional descriptions, longus colli and longus capitis have type I fiber proportions indicative of postural as well as phasic muscle function.

  8. Electrophysiological evidence of doubly innervated branched muscle fibers in the human brachioradialis muscle.

    PubMed

    Lateva, Zoia C; McGill, Kevin C

    2007-12-01

    Motor-unit action potentials (MUAPs) with unstable satellite (late-latency) components are found in EMG signals from the brachioradialis muscles of normal subjects. We analyzed the morphology and blocking behavior of these MUAPs to determine their anatomical origin. EMG signals were recorded from the brachioradialis muscles of 5 normal subjects during moderate-level isometric contractions. MUAP waveforms, discharge patterns, and blocking were determined using computer-aided EMG decomposition. Twelve MUAPs with unstable satellite potentials were detected, always two together in the same signal. Each MUAP also had a second unstable component associated with its main spike. The blocking behavior of the unstable components depended on how close together the two MUAPs were when they discharged. The latencies and blocking behavior indicate that the unstable components came from branched muscle fibers innervated by two different motoneurons. The satellite potentials were due to action potentials that traveled to the branching point along one branch and back along the other. The blockings were due to action-potential collisions when both motoneurons discharged close together in time. Animal studies suggest that branched muscle fibers may be a normal characteristic of series-fibered muscles. This study adds to our understanding of these muscles in humans.

  9. Phenotypic conversion of distinct muscle fiber populations to electrocytes in a weakly electric fish.

    PubMed

    Unguez, G A; Zakon, H H

    1998-09-14

    In most groups of electric fish, the electric organ (EO) derives from striated muscle cells that suppress many muscle phenotypic properties. This phenotypic conversion is recapitulated during regeneration of the tail in the weakly electric fish Sternopygus macrurus. Mature electrocytes, the cells of the electric organ, are considerably larger than the muscle fibers from which they derive, and it is not known whether this is a result of muscle fiber hypertrophy and/or fiber fusion. In this study, electron micrographs revealed fusion of differentiated muscle fibers during the formation of electrocytes. There was no evidence of hypertrophy of muscle fibers during their phenotypic conversion. Furthermore, although fish possess distinct muscle phenotypes, the extent to which each fiber population contributes to the formation of the EO has not been determined. By using myosin ATPase histochemistry and anti-myosin heavy chain (MHC) monoclonal antibodies (mAbs), different fiber types were identified in fascicles of muscle in the adult tail. Mature electrocytes were not stained by the ATPase reaction, nor were they labeled by any of the anti-MHC mAbs. In contrast, mature muscle fibers exhibited four staining patterns. The four fiber types were spatially arranged in distinct compartments with little intermixing; peripherally were two populations of type I fibers with small cross-sectional areas, whereas more centrally were two populations of type II fibers with larger cross-sectional areas. In 2- and 3-week regenerating blastema, three fiber types were clearly discerned. Most (> 95%) early-forming electrocytes had an MHC phenotype similar to that of type II fibers. In contrast, fusion among type I fibers was rare. Together, ultrastructural and immunohistochemical analyses revealed that the fusion of muscle fibers gives rise to electrocytes and that this fusion occurs primarily among the population of type II fibers in regenerating blastema.

  10. Niacin supplementation induces type II to type I muscle fiber transition in skeletal muscle of sheep.

    PubMed

    Khan, Muckta; Couturier, Aline; Kubens, Johanna F; Most, Erika; Mooren, Frank-Christoph; Krüger, Karsten; Ringseis, Robert; Eder, Klaus

    2013-11-22

    It was recently shown that niacin supplementation counteracts the obesity-induced muscle fiber transition from oxidative type I to glycolytic type II and increases the number of type I fibers in skeletal muscle of obese Zucker rats. These effects were likely mediated by the induction of key regulators of fiber transition, PPARδ (encoded by PPARD), PGC-1α (encoded by PPARGC1A) and PGC-1β (encoded by PPARGC1B), leading to type II to type I fiber transition and upregulation of genes involved in oxidative metabolism. The aim of the present study was to investigate whether niacin administration also influences fiber distribution and the metabolic phenotype of different muscles [M. longissimus dorsi (LD), M. semimembranosus (SM), M. semitendinosus (ST)] in sheep as a model for ruminants. For this purpose, 16 male, 11 wk old Rhoen sheep were randomly allocated to two groups of 8 sheep each administered either no (control group) or 1 g niacin per day (niacin group) for 4 wk. After 4 wk, the percentage number of type I fibers in LD, SM and ST muscles was greater in the niacin group, whereas the percentage number of type II fibers was less in niacin group than in the control group (P < 0.05). The mRNA levels of PPARGC1A, PPARGC1B, and PPARD and the relative mRNA levels of genes involved in mitochondrial fatty acid uptake (CPT1B, SLC25A20), tricarboxylic acid cycle (SDHA), mitochondrial respiratory chain (COX5A, COX6A1), and angiogenesis (VEGFA) in LD, SM and ST muscles were greater (P < 0.05) or tended to be greater (P < 0.15) in the niacin group than in the control group. The study shows that niacin supplementation induces muscle fiber transition from type II to type I, and thereby an oxidative metabolic phenotype of skeletal muscle in sheep as a model for ruminants. The enhanced capacity of skeletal muscle to utilize fatty acids in ruminants might be particularly useful during metabolic states in which fatty acids are excessively mobilized from adipose

  11. DNA methylation assessment from human slow- and fast-twitch skeletal muscle fibers

    PubMed Central

    Begue, Gwénaëlle; Raue, Ulrika; Jemiolo, Bozena

    2017-01-01

    A new application of the reduced representation bisulfite sequencing method was developed using low-DNA input to investigate the epigenetic profile of human slow- and fast-twitch skeletal muscle fibers. Successful library construction was completed with as little as 15 ng of DNA, and high-quality sequencing data were obtained with 32 ng of DNA. Analysis identified 143,160 differentially methylated CpG sites across 14,046 genes. In both fiber types, selected genes predominantly expressed in slow or fast fibers were hypomethylated, which was supported by the RNA-sequencing analysis. These are the first fiber type-specific methylation data from human skeletal muscle and provide a unique platform for future research. NEW & NOTEWORTHY This study validates a low-DNA input reduced representation bisulfite sequencing method for human muscle biopsy samples to investigate the methylation patterns at a fiber type-specific level. These are the first fiber type-specific methylation data reported from human skeletal muscle and thus provide initial insight into basal state differences in myosin heavy chain I and IIa muscle fibers among young, healthy men. PMID:28057818

  12. Intramuscular variations of proteome and muscle fiber type distribution in semimembranosus and semitendinosus muscles associated with pork quality.

    PubMed

    Kim, Gap-Don; Yang, Han-Sul; Jeong, Jin-Yeon

    2018-04-01

    Proteome analysis was performed to understand intramuscular variations in muscle fiber distribution in semimembranosus (SM) and semitendinosus (ST) muscles associated with pork quality. Fifteen SM and ST muscles were separated into dark and light portions. The relative area of oxidative fiber was higher (P < .0001) in dark portion than that in light portion, while glycolytic fiber types were distributed primarily (P < .01) in light portions regardless of muscle types. Myosin-1, myosin-4, troponin complex (fast), myosin light chains, and metabolic enzymes responsible for fast-twitch glycolytic types were overexpressed in light portions (P < .05). However, myosin-2, myosin-7, myoglobin, and mitochondrial oxidative metabolic enzymes were closely related to slow-twitch oxidative fibers. These resulted in high pH, redness, and tenderness but low lightness and drip loss of pork quality. In conclusion, differentially expressed muscle proteins are associated with fiber type (oxidative vs. glycolytic) distribution, resulting in intramuscular variations of pork quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Influence of exercise contraction mode and protein supplementation on human skeletal muscle satellite cell content and muscle fiber growth.

    PubMed

    Farup, Jean; Rahbek, Stine Klejs; Riis, Simon; Vendelbo, Mikkel Holm; Paoli, Frank de; Vissing, Kristian

    2014-10-15

    Skeletal muscle satellite cells (SCs) are involved in remodeling and hypertrophy processes of skeletal muscle. However, little knowledge exists on extrinsic factors that influence the content of SCs in skeletal muscle. In a comparative human study, we investigated the muscle fiber type-specific association between emergence of satellite cells (SCs), muscle growth, and remodeling in response to 12 wk unilateral resistance training performed as eccentric (Ecc) or concentric (Conc) resistance training ± whey protein (Whey, 19.5 g protein + 19.5 g glucose) or placebo (Placebo, 39 g glucose) supplementation. Muscle biopsies (vastus lateralis) were analyzed for fiber type-specific SCs, myonuclei, and fiber cross-sectional area (CSA). Following training, SCs increased with Conc in both type I and type II fibers (P < 0.01) and exhibited a group difference from Ecc (P < 0.05), which did not increase. Myonuclei content in type I fibers increased in all groups (P < 0.01), while a specific accretion of myonuclei in type II fibers was observed in the Whey-Conc (P < 0.01) and Placebo-Ecc (P < 0.01) groups. Similarly, whereas type I fiber CSA increased independently of intervention (P < 0.001), type II fiber CSA increased exclusively with Whey-Conc (P < 0.01) and type II fiber hypertrophy correlated with whole muscle hypertrophy exclusively following Conc training (P < 0.01). In conclusion, isolated concentric knee extensor resistance training appears to constitute a stronger driver of SC content than eccentric resistance training while type II fiber hypertrophy was accentuated when combining concentric resistance training with whey protein supplementation. Copyright © 2014 the American Physiological Society.

  14. Degeneration of oxidative muscle fibers in HTLV-1 tax transgenic mice.

    PubMed

    Nerenberg, M I; Wiley, C A

    1989-12-01

    The HTLV-1 tax gene under control of the HTLV-1 long terminal repeat (LTR) was introduced into transgenic mice. Previously tax protein expression in the muscle and peripheral nerves of three independent mouse lines was reported. Here the localization of this transgenic protein at a cellular and subcellular level is described. Tax protein was expressed in oxidative muscle fibers that developed severe progressive atrophy. It localized to the cytoplasma where it was associated with structures resembling degenerating Z bands. This pattern of muscle fiber involvement is similar to that observed in human retroviral associated myopathy. This transgenic mouse model suggests that preferential expression of the HTLV-1 viral promoter in oxidative muscle fibers may explain the productive infection of these fibers in HTLV-1 myopathy.

  15. Remodeling of muscle fibers approaching the human myotendinous junction.

    PubMed

    Jakobsen, J R; Jakobsen, N R; Mackey, A L; Koch, M; Kjaer, M; Krogsgaard, M R

    2018-04-19

    The myotendinous junction (MTJ) is at high risk of strain injuries, due to high amounts of energy that is transferred through this structure. The risk of strain injury is significantly reduced by heavy resistance training (HRT), indicating a remodeling capacity of MTJ. We investigated the degree of remodeling of muscle fibers near the human MTJ. In 8 individuals, samples were taken from the semitendinosus and gracilis MTJ and they were stained immunohistochemically for myonuclei (DAPI), fibroblasts (TCF7L2), and satellite cells (CD56). A high portion of the muscle fibers adjacent to the MTJ contained a centrally located myonucleus (47 ± 8%, mean ± SD) and half of the muscle fibers were CD56 positive. The number of satellite cells and fibroblasts were not higher than what has previously been reported from muscle bellies. The immunohistochemical findings suggest that the rate of remodeling of muscle fibers near the MTJ is very high. The finding that there was no increased number of satellite cells and fibroblasts could be explained as a dynamic phenomenon. The effect of HRT should be evaluated in a randomized setting. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Muscle Fiber Characteristics and Fatty Acid Compositions of the Four Major Muscles in Korean Native Black Goat.

    PubMed

    Hwang, Young-Hwa; Joo, Sung-Hyun; Bakhsh, Allah; Ismail, Ishamri; Joo, Seon-Tea

    2017-01-01

    The objective of this study was to investigate the relationship between muscle fiber characteristics and fatty acid composition of four major muscles in Korean native black goat (KNBG). Longissimus lumborum (LL), psoas major (PM), semimembranosus (SM), and gluteus medius (GM) were obtained from five male KNBGs of 36 mon of age and subjected to histochemical analysis and to determine fatty acid composition and meat quality traits. There were significant ( p <0.05) differences in fiber number percentage (FNP) and fiber area percentage (FAP) of fiber types among these four muscles. PM had the highest FNP of type I and the lowest FNP of type IIB, while SM had the highest FNP of type IIB. The highest fat content was observed in LL while SM had the lowest fat content. The proportions of SFA and MUFA were significantly ( p <0.05) different among four muscles due to differences in the majority of fatty acids such as oleic (C18:1) and palmitic (C16:0) acids. The PUFA/SFA ratio was significantly ( p <0.05) different among four muscles, and the highest PUFA/SFA ratio was observed in PM. Results suggested that LL and PM might be healthful because of higher desirable fatty acid value and PUFA/SFA ratio, respectively. Also, data showed that correlations between muscle fiber types and fatty acids proportion of goat muscles were reversed with those of cattle muscles.

  17. Fiber networks amplify active stress

    PubMed Central

    Ronceray, Pierre; Broedersz, Chase P.

    2016-01-01

    Large-scale force generation is essential for biological functions such as cell motility, embryonic development, and muscle contraction. In these processes, forces generated at the molecular level by motor proteins are transmitted by disordered fiber networks, resulting in large-scale active stresses. Although these fiber networks are well characterized macroscopically, this stress generation by microscopic active units is not well understood. Here we theoretically study force transmission in these networks. We find that collective fiber buckling in the vicinity of a local active unit results in a rectification of stress towards strongly amplified isotropic contraction. This stress amplification is reinforced by the networks’ disordered nature, but saturates for high densities of active units. Our predictions are quantitatively consistent with experiments on reconstituted tissues and actomyosin networks and shed light on the role of the network microstructure in shaping active stresses in cells and tissue. PMID:26921325

  18. Protein Supplementation Does Not Further Increase Latissimus Dorsi Muscle Fiber Hypertrophy after Eight Weeks of Resistance Training in Novice Subjects, but Partially Counteracts the Fast-to-Slow Muscle Fiber Transition.

    PubMed

    Paoli, Antonio; Pacelli, Quirico F; Cancellara, Pasqua; Toniolo, Luana; Moro, Tatiana; Canato, Marta; Miotti, Danilo; Neri, Marco; Morra, Aldo; Quadrelli, Marco; Reggiani, Carlo

    2016-06-01

    The response to resistance training and protein supplementation in the latissimus dorsi muscle (LDM) has never been investigated. We investigated the effects of resistance training (RT) and protein supplementation on muscle mass, strength, and fiber characteristics of the LDM. Eighteen healthy young subjects were randomly assigned to a progressive eight-week RT program with a normal protein diet (NP) or high protein diet (HP) (NP 0.85 vs. HP 1.8 g of protein·kg(-1)·day(-1)). One repetition maximum tests, magnetic resonance imaging for cross-sectional muscle area (CSA), body composition, and single muscle fibers mechanical and phenotype characteristics were measured. RT induced a significant gain in strength (+17%, p < 0.0001), whole muscle CSA (p = 0.024), and single muscle fibers CSA (p < 0.05) of LDM in all subjects. Fiber isometric force increased in proportion to CSA (+22%, p < 0.005) and thus no change in specific tension occurred. A significant transition from 2X to 2A myosin expression was induced by training. The protein supplementation showed no significant effects on all measured outcomes except for a smaller reduction of 2X myosin expression. Our results suggest that in LDM protein supplementation does not further enhance RT-induced muscle fiber hypertrophy nor influence mechanic muscle fiber characteristics but partially counteracts the fast-to-slow fiber shift.

  19. Effects of Nitric Oxide Synthase Inhibition on Fiber-Type Composition, Mitochondrial Biogenesis, and SIRT1 Expression in Rat Skeletal Muscle

    PubMed Central

    Suwa, Masataka; Nakano, Hiroshi; Radak, Zsolt; Kumagai, Shuzo

    2015-01-01

    It was hypothesized that nitric oxide synthases (NOS) regulated SIRT1 expression and lead to a corresponding changes of contractile and metabolic properties in skeletal muscle. The purpose of the present study was to investigate the influence of long-term inhibition of nitric oxide synthases (NOS) on the fiber-type composition, metabolic regulators such as and silent information regulator of transcription 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and components of mitochondrial biogenesis in the soleus and plantaris muscles of rats. Rats were assigned to two groups: control and NOS inhibitor (Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), ingested for 8 weeks in drinking water)-treated groups. The percentage of Type I fibers in the L-NAME group was significantly lower than that in the control group, and the percentage of Type IIA fibers was concomitantly higher in soleus muscle. In plantaris muscle, muscle fiber composition was not altered by L-NAME treatment. L-NAME treatment decreased the cytochrome C protein expression and activity of mitochondrial oxidative enzymes in the plantaris muscle but not in soleus muscle. NOS inhibition reduced the SIRT1 protein expression level in both the soleus and plantaris muscles, whereas it did not affect the PGC-1α protein expression. L-NAME treatment also reduced the glucose transporter 4 protein expression in both muscles. These results suggest that NOS plays a role in maintaining SIRT1 protein expression, muscle fiber composition and components of mitochondrial biogenesis in skeletal muscle. Key points NOS inhibition by L-NAME treatment decreased the SIRT1 protein expression in skeletal muscle. NOS inhibition induced the Type I to Type IIA fiber type transformation in soleus muscle. NOS inhibition reduced the components of mitochondrial biogenesis and glucose metabolism in skeletal muscle. PMID:26336341

  20. Effects of Physical Activity and Inactivity on Muscle Fatigue

    PubMed Central

    Bogdanis, Gregory C.

    2012-01-01

    The aim of this review was to examine the mechanisms by which physical activity and inactivity modify muscle fatigue. It is well known that acute or chronic increases in physical activity result in structural, metabolic, hormonal, neural, and molecular adaptations that increase the level of force or power that can be sustained by a muscle. These adaptations depend on the type, intensity, and volume of the exercise stimulus, but recent studies have highlighted the role of high intensity, short-duration exercise as a time-efficient method to achieve both anaerobic and aerobic/endurance type adaptations. The factors that determine the fatigue profile of a muscle during intense exercise include muscle fiber composition, neuromuscular characteristics, high energy metabolite stores, buffering capacity, ionic regulation, capillarization, and mitochondrial density. Muscle fiber-type transformation during exercise training is usually toward the intermediate type IIA at the expense of both type I and IIx myosin heavy-chain isoforms. High-intensity training results in increases of both glycolytic and oxidative enzymes, muscle capillarization, improved phosphocreatine resynthesis and regulation of K+, H+, and lactate ions. Decreases of the habitual activity level due to injury or sedentary lifestyle result in partial or even compete reversal of the adaptations due to previous training, manifested by reductions in fiber cross-sectional area, decreased oxidative capacity, and capillarization. Complete immobilization due to injury results in markedly decreased force output and fatigue resistance. Muscle unloading reduces electromyographic activity and causes muscle atrophy and significant decreases in capillarization and oxidative enzymes activity. The last part of the review discusses the beneficial effects of intermittent high-intensity exercise training in patients with different health conditions to demonstrate the powerful effect of exercise on health and well being. PMID

  1. Differential apoptosis-related protein expression, mitochondrial properties, proteolytic enzyme activity, and DNA fragmentation between skeletal muscles.

    PubMed

    McMillan, Elliott M; Quadrilatero, Joe

    2011-03-01

    Increased skeletal muscle apoptosis has been associated with a number of conditions including aging, disuse, and cardiovascular disease. Skeletal muscle is a complex tissue comprised of several fiber types with unique properties. To date, no report has specifically examined apoptotic differences across muscles or fiber types. Therefore, we measured several apoptotic indices in healthy rat red (RG) and white gastrocnemius (WG) muscle, as well as examined the expression of several key proteins across fiber types in a mixed muscle (mixed gastrocnemius). The protein content of apoptosis-inducing factor (AIF), apoptosis repressor with caspase recruitment domain (ARC), Bax, Bcl-2, cytochrome c, heat shock protein 70 (Hsp70), and second mitochondria-derived activator of caspases (Smac) were significantly (P < 0.05) higher in RG vs. WG muscle. Cytosolic AIF, cytochrome c, and Smac as well as nuclear AIF were also significantly (P < 0.05) higher in RG compared with WG muscle. In addition, ARC protein expression was related to muscle fiber type and found to be highest (P < 0.001) in type I fibers. Similarly, AIF protein expression was differentially expressed across fibers; however, AIF was correlated to oxidative potential (P < 0.001). Caspase-3, -8, and -9 activity, calpain activity, and DNA fragmentation (a hallmark of apoptosis) were also significantly higher (P < 0.05) in RG compared with WG muscle. Furthermore, total muscle reactive oxygen species generation, as well as Ca(2+)-induced permeability transition pore opening and loss of membrane potential in isolated mitochondria were greater in RG muscle. Collectively, these data suggest that a number of apoptosis-related indices differ between muscles and fiber types. Given these findings, muscle and fiber-type differences in apoptotic protein expression, signaling, and susceptibility should be considered when studying cell death processes in skeletal muscle.

  2. Mitochondrial specialization revealed by single muscle fiber proteomics: focus on the Krebs cycle.

    PubMed

    Schiaffino, S; Reggiani, C; Kostrominova, T Y; Mann, M; Murgia, M

    2015-12-01

    We have developed a highly sensitive mass spectrometry-based proteomic workflow to examine the proteome of single muscle fibers. This study revealed significant differences in the mitochondrial proteome of the four major fiber types present in mouse skeletal muscle. Here, we focus on Krebs cycle enzymes and in particular on the differential distribution of the two mitochondrial isocitrate dehydrogenases, IDH2 and IDH3. Type 1/slow fibers contain high levels of IDH2 and relatively low levels of IDH3, whereas fast 2X and 2B fibers show an opposite expression pattern. The findings suggest that in skeletal muscle, IDH2 functions in the forward direction of the Krebs cycle and that substrate flux along the cycle occurs predominantly via IDH2 in type 1 fibers and via IDH3 in 2X and 2B fibers. IDH2-mediated conversion of isocitrate to α-ketoglutarate leads to the generation of NADPH, which is critical to buffering the H2O2 produced by the respiratory chain. Nicotinamide nucleotide transhydrogenase (NNT), the other major mitochondrial enzyme involved in NADPH generation, is also more abundant in type 1 fibers. We suggest that the continuously active type 1 fibers are endowed with a more efficient H2O2 scavenging capacity to cope with the higher levels of reactive oxygen species production. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Functional effects of uridine triphosphate on human skinned skeletal muscle fibers.

    PubMed

    Vianna-Jorge, R; Oliveira, C F; Mounier, Y; Suarez-Kurtz, G

    1998-02-01

    Chemically skinned human skeletal muscle fibers were used to study the effects of uridine triphosphate (UTP) on the tension-pCa relationship and on Ca2+ uptake and release by the sarcoplasmic reticulum (SR). Total replacement (2.5 mM) of adenosine triphosphate (ATP) with UTP (i) displaced the tension-pCa relationship to the left along the abcissae and increased maximum Ca(2+)-activated tension, both effects being larger in slow- than in fast-type fibers; (ii) markedly reduced Ca2+ uptake by the SR (evaluated by the caffeine-evoked tension) in both fiber types; (iii) had no effect on the rate of depletion of caffeine-sensitive Ca2+ stores during soaking in relaxing solutions; (iv) induced tension in slow- but not in fast-type fibers. The effects on the SR functional properties are consistent with the notion that UTP is a poor substitute for ATP as a substrate for the Ca ATPase pump and as an agonist of the ryanodine-sensitive Ca(2+)-release channel. The UTP-induced tension in human slow-type fibers is attributed to effect(s) of the nucleotide on the tension-pCa relationship of the contractile machinery. The present data reveal important differences between the effects of UTP on human versus rat muscle fibers.

  4. Contractile properties of rat, rhesus monkey, and human type I muscle fibers

    NASA Technical Reports Server (NTRS)

    Widrick, J. J.; Romatowski, J. G.; Karhanek, M.; Fitts, R. H.

    1997-01-01

    It is well known that skeletal muscle intrinsic maximal shortening velocity is inversely related to species body mass. However, there is uncertainty regarding the relationship between the contractile properties of muscle fibers obtained from commonly studied laboratory animals and those obtained from humans. In this study we determined the contractile properties of single chemically skinned fibers prepared from rat, rhesus monkey, and human soleus and gastrocnemius muscle samples under identical experimental conditions. All fibers used for analysis expressed type I myosin heavy chain as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Allometric coefficients for type I fibers from each muscle indicated that there was little change in peak tension (force/fiber cross-sectional area) across species. In contrast, both soleus and gastrocnemius type I fiber maximal unloaded shortening velocity (Vo), the y-intercept of the force-velocity relationship (Vmax), peak power per unit fiber length, and peak power normalized for fiber length and cross-sectional area were all inversely related to species body mass. The present allometric coefficients for soleus fiber Vo (-0.18) and Vmax (-0.11) are in good agreement with published values for soleus fibers obtained from common laboratory and domesticated mammals. Taken together, these observations suggest that the Vo of slow fibers from quadrupeds and humans scale similarly and can be described by the same quantitative relationships. These findings have implications in the design and interpretation of experiments, especially those that use small laboratory mammals as a model of human muscle function.

  5. Localization and regulation of the N terminal splice variant of PGC-1α in adult skeletal muscle fibers.

    PubMed

    Shen, Tiansheng; Liu, Yewei; Schneider, Martin F

    2012-01-01

    The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) regulates expression of genes for metabolism and muscle fiber type. Recently, a novel splice variant of PGC-1α (NT-PGC-1α, amino acids 1-270) was cloned and found to be expressed in muscle. Here we use Flag-tagged NT-PGC-1α to examine the subcellular localization and regulation of NT-PGC-1α in skeletal muscle fibers. Flag-NT-PGC-1α is located predominantly in the myoplasm. Nuclear NT-PGC-1α can be increased by activation of protein kinase A. Activation of p38 MAPK by muscle activity or of AMPK had no effect on the subcellular distribution of NT-PGC-1α. Inhibition of CRM1-mediated export only caused relatively slow nuclear accumulation of NT-PGC-1α, indicating that nuclear export of NT-PGC-1α may be mediated by both CRM1-dependent and -independent pathways. Together these results suggest that the regulation of NT-PGC-1α in muscle fibers may be very different from that of the full-length PGC-1α, which is exclusively nuclear.

  6. Impaired Organization and Function of Myofilaments in Single Muscle Fibers from a Mouse Model of Pompe Disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, S.; Galperin, M; Melvin, G

    Pompe disease, a deficiency of lysosomal acid {alpha}-glucosidase, is a disorder of glycogen metabolism that can affect infants, children, or adults. In all forms of the disease, there is progressive muscle pathology leading to premature death. The pathology is characterized by accumulation of glycogen in lysosomes, autophagic buildup, and muscle atrophy. The purpose of the present investigation was to determine if myofibrillar dysfunction in Pompe disease contributes to muscle weakness beyond that attributed to atrophy. The study was performed on isolated myofibers dissected from severely affected fast glycolytic muscle in the {alpha}-glucosidase knockout mouse model. Psoas muscle fibers were firstmore » permeabilized, so that the contractile proteins could be directly relaxed or activated by control of the composition of the bathing solution. When normalized by cross-sectional area, single fibers from knockout mice produced 6.3 N/cm{sup 2} of maximum Ca{sup 2+}-activated tension compared with 12.0 N/cm{sup 2} produced by wild-type fibers. The total protein concentration was slightly higher in the knockout mice, but concentrations of the contractile proteins myosin and actin remained unchanged. Structurally, X-ray diffraction showed that the actin and myosin filaments, normally arranged in hexagonal arrays, were disordered in the knockout muscle, and a lower fraction of myosin cross bridges was near the actin filaments in the relaxed muscle. The results are consistent with a disruption of actin and myosin interactions in the knockout muscles, demonstrating that impaired myofibrillar function contributes to weakness in the diseased muscle fibers.« less

  7. Analysis of fiber-type differences in reporter gene expression of β-gal transgenic muscle.

    PubMed

    Tai, Phillip W L; Smith, Catherine L; Angello, John C; Hauschka, Stephen D

    2012-01-01

    β-galactosidase (β-gal) is among the most frequently used markers for studying a wide variety of biological mechanisms, e.g., gene expression, cell migration, stem cell conversion to different cell types, and gene silencing. Many of these studies require the histochemical detection of relative β-gal levels in tissue cross-sections mounted onto glass slides and visualized by microscopy. This is particularly useful for the analysis of promoter activity in skeletal muscle tissue since the β-gal levels can vary dramatically between different anatomical muscles and myofiber types. The differences in promoter activity can be due to a myofiber's developmental history, innervation, response to normal or experimental physiological signals, and its disease state. It is thus important to identify the individual fiber types within muscle cross-sections and to correlate these with transgene expression signals. Here, we provide a detailed description of how to process and analyze muscle tissues to determine the fiber-type composition and β-gal transgene expression within cryosections.

  8. THE PASSIVE PROPERTIES OF MUSCLE FIBERS ARE VELOCITY DEPENDENT

    PubMed Central

    Rehorn, Michael R.; Schroer, Alison K.; Blemker, Silvia S.

    2014-01-01

    The passive properties of skeletal muscle play an important role in muscle function. While the passive quasi-static elastic properties of muscle fibers have been well characterized, the dynamic visco-elastic passive behavior of fibers has garnered less attention. In particular, it is unclear how the visco-elastic properties are influenced by lengthening velocity, in particular for the range of physiologically relevant velocities. The goals of this work were to: (i) measure the effects of lengthening velocity on the peak stresses within single muscle fibers to determine how passive behavior changes over a range of physiologically relevant lengthening rates (0.1–10 Lo/s), and (ii) develop a mathematical model of fiber viscoelasticity based on these measurements. We found that passive properties depend on strain rate, in particular at the low loading rates (0.1–3 Lo/s), and that the measured behavior can be predicted across a range of loading rates and time histories with a quasi-linear viscoelastic model. In the future, these results can be used to determine the impact of viscoelastic behavior on intramuscular stresses and forces during a variety of dynamic movements. PMID:24360198

  9. Morphometric analysis of rat muscle fibers following space flight and hypogravity

    NASA Technical Reports Server (NTRS)

    Chui, L. A.; Castleman, K. R.

    1982-01-01

    The effect of hypogravity on striate muscles, containing both fast twitch glycolytic and slow twitch oxidative fibers, was studied in rats aboard two Cosmos biosatellites. Results of a computer-assisted image analysis of extensor digitorum muscles from five rats, exposed to 18.5 days of hypogravity and processed for the alkaline ATPase reaction, showed a reduction of the mean fiber diameter (41.32 + or - 0.55 microns), compared to synchronous (46.32 + or - 0.55 microns) and vivarium (49 + or - 0.5 microns) controls. A further experiment studied the ratio of fast to slow twitch fibers in 25 rats exposed to 18.5 days of hypogravity and analyzed at four different periods of recovery following the space flight. Using the previous techniques, the gastrocnemius muscle showed a reduction of the total muscle fiber area in square microns and a reduction in the percentage of slow fibers of flight animals compared to the control animals.

  10. Selective muscle fiber loss and molecular compensation in mitochondrial myopathy due to TK2 deficiency.

    PubMed

    Vilà, Maya R; Villarroya, Joan; García-Arumí, Elena; Castellote, Amparo; Meseguer, Anna; Hirano, Michio; Roig, Manuel

    2008-04-15

    A 12-year-old patient with mitochondrial DNA (mtDNA) depletion syndrome due to TK2 gene mutations has been evaluated serially over the last 10 years. We observed progressive muscle atrophy with selective loss of type 2 muscle fibers and, despite severe depletion of mtDNA, normal activities of respiratory chain (RC) complexes and levels of COX II mitochondrial protein in the remaining muscle fibers. These results indicate that compensatory mechanisms account for the slow progression of the disease. Identification of factors that ameliorate mtDNA depletion may reveal new therapeutic targets for these devastating disorders.

  11. Catechins activate muscle stem cells by Myf5 induction and stimulate muscle regeneration.

    PubMed

    Kim, A Rum; Kim, Kyung Min; Byun, Mi Ran; Hwang, Jun-Ha; Park, Jung Il; Oh, Ho Taek; Kim, Hyo Kyeong; Jeong, Mi Gyeong; Hwang, Eun Sook; Hong, Jeong-Ho

    2017-07-22

    Muscle weakness is one of the most common symptoms in aged individuals and increases risk of mortality. Thus, maintenance of muscle mass is important for inhibiting aging. In this study, we investigated the effect of catechins, polyphenol compounds in green tea, on muscle regeneration. We found that (-)-epicatechin gallate (ECG) and (-)-epigallocatechin-3-gallate (EGCG) activate satellite cells by induction of Myf5 transcription factors. For satellite cell activation, Akt kinase was significantly induced after ECG treatment and ECG-induced satellite cell activation was blocked in the presence of Akt inhibitor. ECG also promotes myogenic differentiation through the induction of myogenic markers, including Myogenin and Muscle creatine kinase (MCK), in satellite and C2C12 myoblast cells. Finally, EGCG administration to mice significantly increased muscle fiber size for regeneration. Taken together, the results suggest that catechins stimulate muscle stem cell activation and differentiation for muscle regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Transversal stiffness of fibers and desmin content in leg muscles of rats under gravitational unloading of various durations.

    PubMed

    Ogneva, I V

    2010-12-01

    The aim of this research was the analysis of structural changes in various parts of the sarcolemma and contractile apparatus of muscle fibers by measuring their transversal stiffness by atomic force microscopy under gravitational unloading. Soleus, medial gastrocnemius, and tibialis anterior muscles of Wistar rats were the objects of the study. Gravitational unloading was carried out by antiorthostatic suspension of hindlimbs for 1, 3, 7, and 12 days. It was shown that the transversal stiffness of different parts of the contractile apparatus of soleus muscle fibers decreases during gravitational unloading in the relaxed, calcium-activated, and rigor states, the fibers of the medial gastrocnemius show no changes, whereas the transversal stiffness of tibialis anterior muscle increases. Thus the transversal stiffness of the sarcolemma in the relaxed state is reduced in all muscles, which may be due to the direct action of gravity as an external mechanical factor that can influence the tension on a membrane. The change of sarcolemma stiffness in activated fibers, which is due probably to the transfer of tension from the contractile apparatus, correlates with the dynamics of changes in the content of desmin.

  13. Aging Enhances Indirect Flight Muscle Fiber Performance yet Decreases Flight Ability in Drosophila

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, Mark S.; Lekkas, Panagiotis; Braddock, Joan M.

    2008-10-02

    We investigated the effects of aging on Drosophila melanogaster indirect flight muscle from the whole organism to the actomyosin cross-bridge. Median-aged (49-day-old) flies were flight impaired, had normal myofilament number and packing, barely longer sarcomeres, and slight mitochondrial deterioration compared with young (3-day-old) flies. Old (56-day-old) flies were unable to beat their wings, had deteriorated ultrastructure with severe mitochondrial damage, and their skinned fibers failed to activate with calcium. Small-amplitude sinusoidal length perturbation analysis showed median-aged indirect flight muscle fibers developed greater than twice the isometric force and power output of young fibers, yet cross-bridge kinetics were similar. Large increasesmore » in elastic and viscous moduli amplitude under active, passive, and rigor conditions suggest that median-aged fibers become stiffer longitudinally. Small-angle x-ray diffraction indicates that myosin heads move increasingly toward the thin filament with age, accounting for the increased transverse stiffness via cross-bridge formation. We propose that the observed protein composition changes in the connecting filaments, which anchor the thick filaments to the Z-disk, produce compensatory increases in longitudinal stiffness, isometric tension, power and actomyosin interaction in aging indirect flight muscle. We also speculate that a lack of MgATP due to damaged mitochondria accounts for the decreased flight performance.« less

  14. Skeletal muscle fiber size and fiber type distribution in human cancer: Effects of weight loss and relationship to physical function.

    PubMed

    Toth, Michael J; Callahan, Damien M; Miller, Mark S; Tourville, Timothy W; Hackett, Sarah B; Couch, Marion E; Dittus, Kim

    2016-12-01

    Cancer patients frequently experience weight loss, with negative consequences for functionality and prognosis. The extent to which muscle atrophy contributes to weight loss, however, is not clear, as few studies have directly measured muscle fiber morphology in cancer patients. Whole body and regional tissue composition were measured, along with the cross-sectional area (CSA) and fiber type of mechanically-isolated, single muscle fibers, in 19 cancer patients (8 with a history of weight loss, 11 weight-stable) and 15 non-diseased controls. Whole body fat mass was reduced in cancer patients with a history of weight loss, but no differences in whole body or leg fat-free mass were apparent. In contrast, reductions (∼20%) in single muscle fiber CSA were found in both slow-twitch, myosin heavy chain (MHC) I and fast-twitch, MHC IIA fibers in both weight-stable patients and those with a history of weight loss. Fiber type distribution showed a shift towards a fast-twitch phenotype compared to controls, which may preserve muscle function in cancer patients despite atrophy, as positive relationships were found between the fractions of hybrid MHC IIAX and I/IIA fibers and 6-min walk performance. Our results suggest that, although not apparent from whole body or regional measurements, cancer is associated with reduced skeletal muscle fiber size independent of weight loss history and a shift towards fast-twitch fibers, phenotypes that resemble adaptations to muscle disuse. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. Slow-tonic muscle fibers and their potential innervation in the turtle, Pseudemys (Trachemys) scripta elegans.

    PubMed

    Callister, Robert J; Pierce, Patricia A; McDonagh, Jennifer C; Stuart, Douglas G

    2005-04-01

    A description is provided of the ratio of slow-tonic vs. slow- and fast-twitch fibers for five muscles in the adult turtle, Pseudemys (Trachemys) scripta elegans. The cross-sectional area of each fiber type and an estimation of the relative (weighted) cross-sectional area occupied by the different fiber types are also provided. Two hindlimb muscles (flexor digitorum longus, FDL; external gastrocnemius, EG) were selected on the basis of their suitability for future motor-unit studies. Three neck muscles (the fourth head of testo-cervicis, TeC4; the fourth head of retrahens capitus collique, RCCQ4; transversalis cervicis, TrC) were chosen for their progressively decreasing oxidative capacity. Serial sections were stained for myosin adenosine triphosphatase (ATPase), NADH-diaphorase, and alpha-glycerophosphate dehydrogenase (alpha-GPDH). Conventional fiber-type classification was then performed using indirect markers for contraction speed and oxidative (aerobic) vs. glycolytic (anaerobic) metabolism: i.e., slow oxidative (SO, including slow-twitch and possibly slow-tonic fibers), fast-twitch, oxidative-glycolytic (FOG), and fast-twitch glycolytic (Fg) fibers. Slow-tonic fibers in the SO class were then revealed by directing the monoclonal antibody, ALD-58 (raised against the slow-tonic fiber myosin heavy chain of chicken anterior latissimus dorsi), to additional muscle cross sections. All five of the tested muscles contained the four fiber types, with the ATPase-stained fibers including both slow-tonic and slow-twitch fibers. The extreme distributions of SO fibers were in the predominately glycolytic TrC vs. the predominately oxidative TeC4 muscle (TrC-SO, 9%; FOG, 20%; Fg, 71% vs. TeC4-SO, 58%: FOG, 16%; Fg, 25%). Across the five muscles, the relative prevalence of slow-tonic fibers (4-47%) paralleled that of the SO fibers (9-58%). TeC4 had the highest prevalence of slow-tonic fibers (47%). The test muscles exhibited varying degrees of regional concentration of each

  16. Skeletal Muscle-Specific Overexpression of PGC-1α Induces Fiber-Type Conversion through Enhanced Mitochondrial Respiration and Fatty Acid Oxidation in Mice and Pigs.

    PubMed

    Zhang, Lin; Zhou, Ying; Wu, Wangjun; Hou, Liming; Chen, Hongxing; Zuo, Bo; Xiong, Yuanzhu; Yang, Jinzeng

    2017-01-01

    Individual skeletal muscles in the animal body are heterogeneous, as each is comprised of different fiber types. Type I muscle fibers are rich with mitochondria, and have high oxidative metabolisms while type IIB fibers have few mitochondria and high glycolytic metabolic capacity. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a transcriptional co-activator that regulates mitochondrial biogenesis and respiratory function, is implicated in muscle fiber-type switching. Over-expression of PGC-1α in transgenic mice increased the proportion of red/oxidative type I fiber. During pig muscle growth, an increased number of type I fibers can give meat more red color. To explore the roles of PGC-1α in regulation of muscle fiber type conversion, we generated skeletal muscle-specific PGC-1α transgenic mice and pig. Ectopic over-expression of PGC-1α was detected in both fast and slow muscle fibers. The transgenic animals displayed a remarkable amount of red/oxidative muscle fibers in major skeletal muscle tissues. Skeletal muscles from transgenic mice and pigs have increased expression levels of oxidative fiber markers such as MHC1, MHC2x, myoglobin and Tnni1, and decreased expressions of glycolytic fiber genes (MHC2a, MHC2b, CASQ-1 and Tnni2). The genes responsible for the TCA cycle and oxidative phosphorylation, cytochrome coxidase 2 and 4, and citrate synthase were also increased in the transgenic mice and pigs. These results suggested that transgenic over-expressed PGC-1α significantly increased muscle mitochondrial biogenesis, resulting in qualitative changes from glycolytic to oxidative energy generation. The transgenic animals also had elevated levels of PDK4 and PPARγ proteins in muscle tissue, which can lead to increased glycogen deposition and fatty acid oxidation. Therefore, the results support a significant role of PGC-1α in conversion of fast glycolytic fibers to slow and oxidative fiber through enhanced mitochondrial respiration

  17. Fiber-specific regulation of Ca(2+)-ATPase isoform expression by thyroid hormone in rat skeletal muscle.

    PubMed

    van der Linden, C G; Simonides, W S; Muller, A; van der Laarse, W J; Vermeulen, J L; Zuidwijk, M J; Moorman, A F; van Hardeveld, C

    1996-12-01

    We studied the effect of thyroid hormone (3,5,3'-triiodo-L-thyronine, T3) on the expression of sarcoplasmic reticulum (SR) fast- and slow-type Ca(2+)-ATPase isoforms, SERCA1 and SERCA2a, respectively, and total SR Ca(2+)-ATPase activity in rat skeletal muscle. Cross sections and homogenates of soleus and extensor digitorum longus muscles from hypo-, eu-, and hyperthyroid rats were examined, and expression of Ca(2+)-ATPase isoforms in individual fibers was compared with expression of fast (MHC II) and slow (MHC I) myosin heavy chain isoforms. In both muscles, T3 induced a coordinated and full conversion to a fast-twitch phenotype in one-half of the fibers that were slow twitch in the absence of T3. The conversion was partial in the other one-half of the fibers, giving rise to a mixed phenotype. The stimulation by T3 of total SERCA expression in all fibers was reflected by increased SR Ca(2+)-ATPase activity. The time course of the T3-induced changes of SERCA isoform expression was examined 1-14 days after the start of daily T3 treatment of euthyroid rats. SERCA1 expression was stimulated by T3 at a pretranslational level in all fibers. SERCA2a mRNA expression was transiently stimulated and disappeared in a subset of fibers. In these fibers SR Ca(2+)-ATPase activity was high because of high SERCA1 protein levels. These data suggest that the ultimate downregulation of SERCA2a expression, which is always associated with high SR Ca(2+)-ATPase activities, occurs at a pretranslational level.

  18. Overexpression of the Mitochondrial T3 Receptor p43 Induces a Shift in Skeletal Muscle Fiber Types

    PubMed Central

    Casas, François; Pessemesse, Laurence; Grandemange, Stéphanie; Seyer, Pascal; Gueguen, Naïg; Baris, Olivier; Lepourry, Laurence; Cabello, Gérard; Wrutniak-Cabello, Chantal

    2008-01-01

    In previous studies, we have characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43) acting as a mitochondrial transcription factor and consequently stimulating mitochondrial activity and mitochondrial biogenesis. We have established the involvement of this T3 pathway in the regulation of in vitro myoblast differentiation.We have generated mice overexpressing p43 under control of the human α-skeletal actin promoter. In agreement with the previous characterization of this promoter, northern-blot and western-blot experiments confirmed that after birth p43 was specifically overexpressed in skeletal muscle. As expected from in vitro studies, in 2-month old mice, p43 overexpression increased mitochondrial genes expression and mitochondrial biogenesis as attested by the increase of mitochondrial mass and mt-DNA copy number. In addition, transgenic mice had a body temperature 0.8°C higher than control ones and displayed lower plasma triiodothyronine levels. Skeletal muscles of transgenic mice were redder than wild-type animals suggesting an increased oxidative metabolism. In line with this observation, in gastrocnemius, we recorded a strong increase in cytochrome oxidase activity and in mitochondrial respiration. Moreover, we observed that p43 drives the formation of oxidative fibers: in soleus muscle, where MyHC IIa fibers were partly replaced by type I fibers; in gastrocnemius muscle, we found an increase in MyHC IIa and IIx expression associated with a reduction in the number of glycolytic fibers type IIb. In addition, we found that PGC-1α and PPARδ, two major regulators of muscle phenotype were up regulated in p43 transgenic mice suggesting that these proteins could be downstream targets of mitochondrial activity. These data indicate that the direct mitochondrial T3 pathway is deeply involved in the acquisition of contractile and metabolic features of muscle fibers in particular by regulating PGC-1α and PPARδ. PMID:18575627

  19. Technique for quantitative RT-PCR analysis directly from single muscle fibers.

    PubMed

    Wacker, Michael J; Tehel, Michelle M; Gallagher, Philip M

    2008-07-01

    The use of single-cell quantitative RT-PCR has greatly aided the study of gene expression in fields such as muscle physiology. For this study, we hypothesized that single muscle fibers from a biopsy can be placed directly into the reverse transcription buffer and that gene expression data can be obtained without having to first extract the RNA. To test this hypothesis, biopsies were taken from the vastus lateralis of five male subjects. Single muscle fibers were isolated and underwent RNA isolation (technique 1) or placed directly into reverse transcription buffer (technique 2). After cDNA conversion, individual fiber cDNA was pooled and quantitative PCR was performed using primer-probes for beta(2)-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, insulin-like growth factor I receptor, and glucose transporter subtype 4. The no RNA extraction method provided similar quantitative PCR data as that of the RNA extraction method. A third technique was also tested in which we used one-quarter of an individual fiber's cDNA for PCR (not pooled) and the average coefficient of variation between fibers was <8% (cycle threshold value) for all genes studied. The no RNA extraction technique was tested on isolated muscle fibers using a gene known to increase after exercise (pyruvate dehydrogenase kinase 4). We observed a 13.9-fold change in expression after resistance exercise, which is consistent with what has been previously observed. These results demonstrate a successful method for gene expression analysis directly from single muscle fibers.

  20. Niacin supplementation increases the number of oxidative type I fibers in skeletal muscle of growing pigs

    PubMed Central

    2013-01-01

    Background A recent study showed that niacin supplementation counteracts the obesity-induced muscle fiber switching from oxidative type I to glycolytic type II and increases the number of type I fibers in skeletal muscle of obese Zucker rats. These effects were likely mediated by the induction of key regulators of fiber transition, PGC-1α and PGC-1β, leading to muscle fiber switching and up-regulation of genes involved in mitochondrial fatty acid import and oxidation, citrate cycle, oxidative phosphorylation, mitochondrial biogenesis. The aim of the present study was to investigate whether niacin supplementation causes type II to type I muscle and changes the metabolic phenotype of skeletal muscles in growing pigs. Results 25 male, 11 wk old crossbred pigs (Danzucht x Pietrain) with an average body weight of 32.8 ± 1.3 (mean ± SD) kg were randomly allocated to two groups of 12 (control group) and 13 pigs (niacin group) which were fed either a control diet or a diet supplemented with 750 mg niacin/kg diet. After 3 wk, the percentage number of type I fibers in three different muscles (M. longissismus dorsi, M. quadriceps femoris, M. gastrocnemius) was greater in the niacin group and the percentage number of type II fibers was lower in the niacin group than in the control group (P < 0.05). The mRNA levels of PGC-1β and genes involved in mitochondrial fatty acid catabolism (CACT, FATP1, OCTN2), citrate cycle (SDHA), oxidative phosphorylation (COX4/1, COX6A1), and thermogenesis (UCP3) in M. longissimus dorsi were greater in the niacin group than in the control group (P < 0.05). Conclusions The study demonstrates that niacin supplementation induces type II to type I muscle fiber switching, and thereby an oxidative metabolic phenotype of skeletal muscle in pigs. Given that oxidative muscle types tend to develop dark, firm and dry pork in response to intense physical activity and/or high psychological stress levels preslaughter, a niacin

  1. Automated muscle fiber type population analysis with ImageJ of whole rat muscles using rapid myosin heavy chain immunohistochemistry.

    PubMed

    Bergmeister, Konstantin D; Gröger, Marion; Aman, Martin; Willensdorfer, Anna; Manzano-Szalai, Krisztina; Salminger, Stefan; Aszmann, Oskar C

    2016-08-01

    Skeletal muscle consists of different fiber types which adapt to exercise, aging, disease, or trauma. Here we present a protocol for fast staining, automatic acquisition, and quantification of fiber populations with ImageJ. Biceps and lumbrical muscles were harvested from Sprague-Dawley rats. Quadruple immunohistochemical staining was performed on single sections using antibodies against myosin heavy chains and secondary fluorescent antibodies. Slides were scanned automatically with a slide scanner. Manual and automatic analyses were performed and compared statistically. The protocol provided rapid and reliable staining for automated image acquisition. Analyses between manual and automatic data indicated Pearson correlation coefficients for biceps of 0.645-0.841 and 0.564-0.673 for lumbrical muscles. Relative fiber populations were accurate to a degree of ± 4%. This protocol provides a reliable tool for quantification of muscle fiber populations. Using freely available software, it decreases the required time to analyze whole muscle sections. Muscle Nerve 54: 292-299, 2016. © 2016 Wiley Periodicals, Inc.

  2. Myoglobin plasma level related to muscle mass and fiber composition: a clinical marker of muscle wasting?

    PubMed

    Weber, Marc-André; Kinscherf, Ralf; Krakowski-Roosen, Holger; Aulmann, Michael; Renk, Hanna; Künkele, Annette; Edler, Lutz; Kauczor, Hans-Ulrich; Hildebrandt, Wulf

    2007-08-01

    Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r = 0.65, p < 0.001) and to the CSA fraction formed by type 1 and 2a fibers (r = 0.80, p < 0.001). However, when adjusted for body height and age by multiple regression, MG yielded a largely improved prediction of total CSA (multiple r = 0.83, p < 0.001) and of fiber type 1 and 2a CSA (multiple r = 0.89, p < 0.001). The correlations between CK and these muscle parameters were weaker, and elevated CK values were observed in 20% of control subjects despite a prior abstinence from exercise for 5 days. In conclusion, plasma MG, when adjusted for anthropometric parameters unaffected by weight, may be considered as a novel marker of muscle mass (CSA) indicating best the mass of MG-rich type 1 and 2a fibers as well as VO(2)max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer

  3. The effect of caloric restriction on the forelimb skeletal muscle fibers of the hypertrophic myostatin null mice.

    PubMed

    Elashry, Mohamed I; Matsakas, Antonios; Wenisch, Sabine; Arnhold, Stefan; Patel, Ketan

    2017-06-01

    Skeletal muscle mass loss has a broad impact on body performance and physical activity. Muscle wasting occurs due to genetic mutation as in muscular dystrophy, age-related muscle loss (sarcopenia) as well as in chronic wasting disorders as in cancer cachexia. Food restriction reduces muscle mass underpinned by increased muscle protein break down. However the influence of dietary restriction on the morphometry and phenotype of forelimb muscles in a genetically modified myostatin null mice are not fully characterized. The effect of a five week dietary limitation on five anatomically and structurally different forelimb muscles was examined. C57/BL6 wild type (Mstn +/+ ) and myostatin null (Mstn -/- ) mice were either given a standard rodent normal daily diet ad libitum (ND) or 60% food restriction (FR) for a 5 week period. M. triceps brachii Caput laterale (T.lateral), M. triceps brachii Caput longum (T.long), M. triceps brachii Caput mediale (T.medial), M. extensor carpi ulnaris (ECU) and M. flexor carpi ulnaris (FCU) were dissected, weighted and processed for immunohistochemistry. Muscle mass, fibers cross sectional areas (CSA) and myosin heavy chain types IIB, IIX, IIA and type I were analyzed. We provide evidence that caloric restriction results in muscle specific weight reduction with the fast myofibers being more prone to atrophy. We show that slow fibers are less liable to dietary restriction induced muscle atrophy. The effect of dietary restriction was more pronounced in Mstn -/- muscles to implicate the oxidative fibers compared to Mstn +/+ . Furthermore, peripherally located myofibers are more susceptible to dietary induced reduction compared to deep fibers. We additionally report that dietary restriction alters the glycolytic phenotype of the Mstn -/- into the oxidative form in a muscle dependent manner. In summary our study shows that calorie restriction alters muscle fiber profile of forelimb muscles of Myostatin null mice. Copyright © 2017 Elsevier Gmb

  4. Supplementing healthy rats with a high-niacin dose has no effect on muscle fiber distribution and muscle metabolic phenotype.

    PubMed

    Scholz, Kristen; Kynast, Anna Marie; Couturier, Aline; Mooren, Frank-Christoph; Krüger, Karsten; Most, Erika; Eder, Klaus; Ringseis, Robert

    2014-08-01

    It was recently shown that niacin prevents the obesity-induced type I to type II fiber switching in skeletal muscle of obese rats and favors the development of a more oxidative metabolic phenotype and thereby increases whole body utilization of fatty acids. Whether niacin also causes type II to type I fiber switching in skeletal muscle of healthy rats has not been investigated yet. Thus, the present study aimed to investigate whether niacin supplementation influences fiber distribution and metabolic phenotype of different skeletal muscles with a distinct type I-to-type II fiber ratio in healthy rats. Twenty-four male, 10-week-old Sprague-Dawley rats were randomly assigned into two groups of 12 rats each and fed either a control diet with 30 mg supplemented niacin/kg diet (control group) or a high-niacin diet with 780 mg supplemented niacin/kg diet (high-niacin group). After 27 days of treatment, the percentage number of type I fibers in rectus femoris, gastrocnemius, and tibialis anterior muscles was 5-10% greater in the niacin group than in the control group, but did not differ between groups in soleus and vastus intermedius muscles. Transcript levels of genes encoding transcription factors regulating fiber switching, fiber-specific myosin heavy chain isoforms, and proteins involved in fatty acid utilization, oxidative phosphorylation, and angiogenesis did not differ between groups. The results show that niacin has only negligible effects on fiber distribution and its regulation as well as the metabolic phenotype of skeletal muscle in healthy rats.

  5. Orai1 enhances muscle endurance by promoting fatigue-resistant type I fiber content but not through acute store-operated Ca2+ entry

    PubMed Central

    Carrell, Ellie M.; Coppola, Aundrea R.; McBride, Helen J.; Dirksen, Robert T.

    2016-01-01

    Orai1 is a transmembrane protein that forms homomeric, calcium-selective channels activated by stromal interaction molecule 1 (STIM1) after depletion of intracellular calcium stores. In adult skeletal muscle, depletion of sarcoplasmic reticulum calcium activates STIM1/Orai1-dependent store-operated calcium entry. Here, we used constitutive and inducible muscle-specific Orai1-knockout (KO) mice to determine the acute and long-term developmental effects of Orai1 ablation on muscle structure and function. Skeletal muscles from constitutive, muscle-specific Orai-KO mice exhibited normal postnatal growth and fiber type differentiation. However, a significant reduction in fiber cross-sectional area occurred by 3 mo of age, with the most profound reduction observed in oxidative, fatigue-resistant fiber types. Soleus muscles of constitutive Orai-KO mice exhibited a reduction in unique type I fibers, concomitant with an increase in hybrid fibers expressing both type I and type IIA myosins. Additionally, ex vivo force measurements showed reduced maximal specific force and in vivo exercise assays revealed reduced endurance in constitutive muscle-specific Orai-KO mice. Using tamoxifen-inducible, muscle-specific Orai-KO mice, these functional deficits were found to be the result of the delayed fiber changes resulting from an early developmental loss of Orai1 and not the result of an acute loss of Orai1-dependent store-operated calcium entry.—Carrell, E. M., Coppola, A. R., McBride, H. J., Dirksen, R. T. Orai1 enhances muscle endurance by promoting fatigue-resistant type I fiber content but not through acute store-operated Ca2+ entry. PMID:27587568

  6. Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function

    NASA Technical Reports Server (NTRS)

    Widrick, J. J.; Trappe, S. W.; Romatowski, J. G.; Riley, D. A.; Costill, D. L.; Fitts, R. H.

    2002-01-01

    We used Ca2+-activated skinned muscle fibers to test the hypothesis that unilateral lower leg suspension (ULLS) alters cross-bridge mechanisms of muscle contraction. Soleus and gastrocnemius biopsies were obtained from eight subjects before ULLS, immediately after 12 days of ULLS (post-0 h), and after 6 h of reambulation (post-6 h). Post-0 h soleus fibers expressing type I myosin heavy chain (MHC) showed significant reductions in diameter, absolute and specific peak Ca2+-activated force, unloaded shortening velocity, and absolute and normalized peak power. Fibers obtained from the gastrocnemius were less affected by ULLS, particularly fibers expressing fast MHC isoforms. Post-6 h soleus fibers produced less absolute and specific peak force than did post-0 h fibers, suggesting that reambulation after ULLS induced cell damage. Like bed rest and spaceflight, ULLS primarily affects soleus over gastrocnemius fibers. However, in contrast to these other models, slow soleus fibers obtained after ULLS showed a decrease in unloaded shortening velocity and a greater reduction in specific force.

  7. MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type

    PubMed Central

    Wu, Hai; Naya, Francisco J.; McKinsey, Timothy A.; Mercer, Brian; Shelton, John M.; Chin, Eva R.; Simard, Alain R.; Michel, Robin N.; Bassel-Duby, Rhonda; Olson, Eric N.; Williams, R. Sanders

    2000-01-01

    Different patterns of motor nerve activity drive distinctive programs of gene transcription in skeletal muscles, thereby establishing a high degree of metabolic and physiological specialization among myofiber subtypes. Recently, we proposed that the influence of motor nerve activity on skeletal muscle fiber type is transduced to the relevant genes by calcineurin, which controls the functional activity of NFAT (nuclear family of activated T cell) proteins. Here we demonstrate that calcineurin-dependent gene regulation in skeletal myocytes is mediated also by MEF2 transcription factors, and is integrated with additional calcium-regulated signaling inputs, specifically calmodulin-dependent protein kinase activity. In skeletal muscles of transgenic mice, both NFAT and MEF2 binding sites are necessary for properly regulated function of a slow fiber-specific enhancer, and either forced expression of activated calcineurin or motor nerve stimulation up-regulates a MEF2-dependent reporter gene. These results provide new insights into the molecular mechanisms by which specialized characteristics of skeletal myofiber subtypes are established and maintained. PMID:10790363

  8. Myosin content of individual human muscle fibers isolated by laser capture microdissection.

    PubMed

    Stuart, Charles A; Stone, William L; Howell, Mary E A; Brannon, Marianne F; Hall, H Kenton; Gibson, Andrew L; Stone, Michael H

    2016-03-01

    Muscle fiber composition correlates with insulin resistance, and exercise training can increase slow-twitch (type I) fibers and, thereby, mitigate diabetes risk. Human skeletal muscle is made up of three distinct fiber types, but muscle contains many more isoforms of myosin heavy and light chains, which are coded by 15 and 11 different genes, respectively. Laser capture microdissection techniques allow assessment of mRNA and protein content in individual fibers. We found that specific human fiber types contain different mixtures of myosin heavy and light chains. Fast-twitch (type IIx) fibers consistently contained myosin heavy chains 1, 2, and 4 and myosin light chain 1. Type I fibers always contained myosin heavy chains 6 and 7 (MYH6 and MYH7) and myosin light chain 3 (MYL3), whereas MYH6, MYH7, and MYL3 were nearly absent from type IIx fibers. In contrast to cardiomyocytes, where MYH6 (also known as α-myosin heavy chain) is seen solely in fast-twitch cells, only slow-twitch fibers of skeletal muscle contained MYH6. Classical fast myosin heavy chains (MHC1, MHC2, and MHC4) were present in variable proportions in all fiber types, but significant MYH6 and MYH7 expression indicated slow-twitch phenotype, and the absence of these two isoforms determined a fast-twitch phenotype. The mixed myosin heavy and light chain content of type IIa fibers was consistent with its role as a transition between fast and slow phenotypes. These new observations suggest that the presence or absence of MYH6 and MYH7 proteins dictates the slow- or fast-twitch phenotype in skeletal muscle. Copyright © 2016 the American Physiological Society.

  9. Myosin content of individual human muscle fibers isolated by laser capture microdissection

    PubMed Central

    Stone, William L.; Howell, Mary E. A.; Brannon, Marianne F.; Hall, H. Kenton; Gibson, Andrew L.; Stone, Michael H.

    2015-01-01

    Muscle fiber composition correlates with insulin resistance, and exercise training can increase slow-twitch (type I) fibers and, thereby, mitigate diabetes risk. Human skeletal muscle is made up of three distinct fiber types, but muscle contains many more isoforms of myosin heavy and light chains, which are coded by 15 and 11 different genes, respectively. Laser capture microdissection techniques allow assessment of mRNA and protein content in individual fibers. We found that specific human fiber types contain different mixtures of myosin heavy and light chains. Fast-twitch (type IIx) fibers consistently contained myosin heavy chains 1, 2, and 4 and myosin light chain 1. Type I fibers always contained myosin heavy chains 6 and 7 (MYH6 and MYH7) and myosin light chain 3 (MYL3), whereas MYH6, MYH7, and MYL3 were nearly absent from type IIx fibers. In contrast to cardiomyocytes, where MYH6 (also known as α-myosin heavy chain) is seen solely in fast-twitch cells, only slow-twitch fibers of skeletal muscle contained MYH6. Classical fast myosin heavy chains (MHC1, MHC2, and MHC4) were present in variable proportions in all fiber types, but significant MYH6 and MYH7 expression indicated slow-twitch phenotype, and the absence of these two isoforms determined a fast-twitch phenotype. The mixed myosin heavy and light chain content of type IIa fibers was consistent with its role as a transition between fast and slow phenotypes. These new observations suggest that the presence or absence of MYH6 and MYH7 proteins dictates the slow- or fast-twitch phenotype in skeletal muscle. PMID:26676053

  10. Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

    PubMed

    Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

    2013-05-20

    Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

  11. Age-related conversion of dystrophin-negative to -positive fiber segments of skeletal but not cardiac muscle fibers in heterozygote mdx mice.

    PubMed

    Karpati, G; Zubrzycka-Gaarn, E E; Carpenter, S; Bulman, D E; Ray, P N; Worton, R G

    1990-03-01

    Immunoreactive dystrophin was examined in muscle fibers of quadriceps, extraocular muscles and cardiac ventricular muscles of female heterozygote mdx mice at 10, 35 and 60 days of age, with microscopic immunoperoxidase method and by immunoblots. In quadriceps muscle fibers there was a marked gradual diminution of the dystrophin-negative fiber segments between age 10 and 60 days. We suggest that this was partly due to a spontaneous fusion of dystrophin-competent satellite cells into the dystrophin-negative fiber segments and partly to an expansion of the cytoplasmic domain of dystrophin expression related to the original myonuclei. In cardiac muscle that lacks satellite cells, there was persistence of a large number of dystrophin-negative fiber segments even at age 60 days and probably beyond. The findings of this study have implications for the detection of heterozygote female carriers of Duchenne muscular dystrophy (DMD) and for the possible therapy of DMD muscles by myoblast transfer.

  12. Enzymatically modified isoquercitrin supplementation intensifies plantaris muscle fiber hypertrophy in functionally overloaded mice.

    PubMed

    Kohara, Akiko; Machida, Masanao; Setoguchi, Yuko; Ito, Ryouichi; Sugitani, Masanori; Maruki-Uchida, Hiroko; Inagaki, Hiroyuki; Ito, Tatsuhiko; Omi, Naomi; Takemasa, Tohru

    2017-01-01

    Enzymatically modified isoquercitrin (EMIQ) is produced from rutin using enzymatic hydrolysis followed by treatment with glycosyltransferase in the presence of dextrin to add glucose residues. EMIQ is absorbed in the same way as quercetin, a powerful antioxidant reported to prevent disused muscle atrophy by targeting mitochondria and to have ergogenic effects. The present study investigated the effect of EMIQ on skeletal muscle hypertrophy induced by functional overload. In Study 1, 6-week-old ICR male mice were divided into 4 groups: sham-operated control, sham-operated EMIQ, overload-operated control, and overload-operated EMIQ groups. In Study 2, mice were divided into 3 groups: overload-operated whey control, overload-operated whey/EMIQ (low dose), and overload-operated whey/EMIQ (high dose) groups. The functional overload of the plantaris muscle was induced by ablation of the synergist (gastrocnemius and soleus) muscles. EMIQ and whey protein were administered with food. Three weeks after the operation, the cross-sectional area and minimal fiber diameter of the plantaris muscle fibers were measured. In Study 1, functional overload increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ supplementation significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle in both the sham-operated and overload-operated groups. In Study 2, EMIQ supplementation combined with whey protein administration significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ, even when administered as an addition to whey protein supplementation, significantly intensified the fiber hypertrophy of the plantaris muscle in functionally overloaded mice. EMIQ supplementation also induced fiber hypertrophy of the plantaris in sham-operated mice.

  13. Structural dynamics of the skeletal muscle fiber by second harmonic generation

    NASA Astrophysics Data System (ADS)

    Nucciotti, V.; Stringari, C.; Sacconi, L.; Vanzi, F.; Linari, M.; Piazzesi, G.; Lombardi, V.; Pavone, F. S.

    2008-02-01

    The high degree of structural order in skeletal muscle allows imaging of this tissue by Second Harmonic Generation (SHG). As previously found (Vanzi et al., J. Muscle Cell Res. Motil. 2006) by fractional extraction of proteins, myosin is the source of SHG signal. A full characterization of the polarization-dependence of the SHG signal can provide very selective information on the orientation of the emitting proteins and their dynamics during contraction. We developed a line scan polarization method, allowing measurements of a full polarization curve in intact muscle fibers from skeletal muscle of the frog to characterize the SHG polarization dependence on different physiological states (resting, rigor and isometric tetanic contraction). The polarization data have been interpreted by means of a model in terms of the average orientation of SHG emitters.The different physiological states are characterized by distinct patterns of SHG polarization. The variation of the orientation of emitting molecules in relation to the physiological state of the muscle demonstrates that one part of SHG signal arises from the globular head of the myosin molecule that cross-links actin and myosin filaments. The dependence of the SHG modulation on the degree of overlap between actin and myosin filaments during an isometric contraction, provides the constraints to estimate the fraction of myosin heads generating the isometric force in the active muscle fiber.

  14. The Drosophila indirect flight muscle myosin heavy chain isoform is insufficient to transform the jump muscle into a highly stretch-activated muscle type

    PubMed Central

    Zhao, Cuiping

    2017-01-01

    Stretch activation (SA) is a delayed increase in force that enables high power and efficiency from a cyclically contracting muscle. SA exists in various degrees in almost all muscle types. In Drosophila, the indirect flight muscle (IFM) displays exceptionally high SA force production (FSA), whereas the jump muscle produces only minimal FSA. We previously found that expressing an embryonic (EMB) myosin heavy chain (MHC) isoform in the jump muscle transforms it into a moderately SA muscle type and enables positive cyclical power generation. To investigate whether variation in MHC isoforms is sufficient to produce even higher FSA, we substituted the IFM MHC isoform (IFI) into the jump muscle. Surprisingly, we found that IFI only caused a 1.7-fold increase in FSA, less than half the increase previously observed with EMB, and only at a high Pi concentration, 16 mM. This IFI-induced FSA is much less than what occurs in IFM, relative to isometric tension, and did not enable positive cyclical power generation by the jump muscle. Both isometric tension and FSA of control fibers decreased with increasing Pi concentration. However, for IFI-expressing fibers, only isometric tension decreased. The rate of FSA generation was ~1.5-fold faster for IFI fibers than control fibers, and both rates were Pi dependent. We conclude that MHC isoforms can alter FSA and hence cyclical power generation but that isoforms can only endow a muscle type with moderate FSA. Highly SA muscle types, such as IFM, likely use a different or additional mechanism. PMID:27881413

  15. Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term.

    PubMed

    Yates, Dustin T; Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Macko, Antoni R; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

    2016-06-01

    Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller (P < 0.05) than controls and exhibited hypoxemia and hypoglycemia, which contributed to 6.9-fold greater (P < 0.05) plasma norepinephrine and ∼53% lower (P < 0.05) plasma insulin concentrations. IUGR semitendinosus muscles contained less (P < 0.05) myosin heavy chain-I protein (MyHC-I) and proportionally fewer (P < 0.05) Type I and Type I/IIa fibers than controls, but MyHC-II protein concentrations, Type II fibers, and Type IIx fibers were not different. IUGR biceps femoris muscles exhibited similar albeit less dramatic differences in fiber type proportions. Type I and IIa fibers are more responsive to adrenergic and insulin regulation than Type IIx and may be more profoundly impaired by the high catecholamines and low insulin in our IUGR fetuses, leading to their proportional reduction. In both muscles, fibers of each type were uniformly smaller (P < 0.05) in IUGR fetuses than controls, which indicates that fiber hypertrophy is not dependent on type but rather on other factors such as myoblast differentiation or protein synthesis. Together, our findings show that IUGR fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance. Copyright © 2016 the American Physiological Society.

  16. Differential Responses of Soleus and Plantaris Muscle Fibers to Overloading

    NASA Astrophysics Data System (ADS)

    Kawano, Fuminori; Shibaguchi, Tsubasa; Ohira, Takashi; Nakai, Naoya; Ohira, Yoshinobu

    2013-02-01

    Responses of slow and fast fibers in soleus and plantaris muscles of adult rats to overloading by the tendon transection of synergists were studied. Overloading-related hypertrophy was noted in the slow fibers of plantaris and soleus, although the magnitude was greater in plantaris. Five genes with minor expression in slow soleus muscle were identified by microarray analysis. Base-line expressions of these genes in slow fibers of plantaris were also low. Further, repressive effects of overloading on these genes were seen in some fast fibers of plantaris, not in whole plantaris and soleus. The data suggested that the repression of particular genes might be related to the pronounced morphological response of fibers expressing type II, including I+II, myosin heavy chain (MyHC), although these genes with lower base-line expression in slow fibers did not respond to overloading.

  17. The role of Sox6 in zebrafish muscle fiber type specification.

    PubMed

    Jackson, Harriet E; Ono, Yosuke; Wang, Xingang; Elworthy, Stone; Cunliffe, Vincent T; Ingham, Philip W

    2015-01-01

    The transcription factor Sox6 has been implicated in regulating muscle fiber type-specific gene expression in mammals. In zebrafish, loss of function of the transcription factor Prdm1a results in a slow to fast-twitch fiber type transformation presaged by ectopic expression of sox6 in slow-twitch progenitors. Morpholino-mediated Sox6 knockdown can suppress this transformation but causes ectopic expression of only one of three slow-twitch specific genes assayed. Here, we use gain and loss of function analysis to analyse further the role of Sox6 in zebrafish muscle fiber type specification. The GAL4 binary misexpression system was used to express Sox6 ectopically in zebrafish embryos. Cis-regulatory elements were characterized using transgenic fish. Zinc finger nuclease mediated targeted mutagenesis was used to analyse the effects of loss of Sox6 function in embryonic, larval and adult zebrafish. Zebrafish transgenic for the GCaMP3 Calcium reporter were used to assay Ca2+ transients in wild-type and mutant muscle fibres. Ectopic Sox6 expression is sufficient to downregulate slow-twitch specific gene expression in zebrafish embryos. Cis-regulatory elements upstream of the slow myosin heavy chain 1 (smyhc1) and slow troponin c (tnnc1b) genes contain putative Sox6 binding sites required for repression of the former but not the latter. Embryos homozygous for sox6 null alleles expressed tnnc1b throughout the fast-twitch muscle whereas other slow-specific muscle genes, including smyhc1, were expressed ectopically in only a subset of fast-twitch fibers. Ca2+ transients in sox6 mutant fast-twitch fibers were intermediate in their speed and amplitude between those of wild-type slow- and fast-twitch fibers. sox6 homozygotes survived to adulthood and exhibited continued misexpression of tnnc1b as well as smaller slow-twitch fibers. They also exhibited a striking curvature of the spine. The Sox6 transcription factor is a key regulator of fast-twitch muscle fiber differentiation

  18. Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears.

    PubMed

    Mendias, Christopher L; Roche, Stuart M; Harning, Julie A; Davis, Max E; Lynch, Evan B; Sibilsky Enselman, Elizabeth R; Jacobson, Jon A; Claflin, Dennis R; Calve, Sarah; Bedi, Asheesh

    2015-01-01

    A persistent atrophy of muscle fibers and an accumulation of fat, collectively referred to as fatty degeneration, commonly occur in patients with chronic rotator cuff tears. The etiology of fatty degeneration and function of the residual rotator cuff musculature have not been well characterized in humans. We hypothesized that muscles from patients with chronic rotator cuff tears have reduced muscle fiber force production, disordered myofibrils, and an accumulation of fat vacuoles. The contractility of muscle fibers from biopsy specimens of supraspinatus muscles of 13 patients with chronic full-thickness posterosuperior rotator cuff tears was measured and compared with data from healthy vastus lateralis muscle fibers. Correlations between muscle fiber contractility, American Shoulder and Elbow Surgeons (ASES) scores, and tear size were analyzed. Histology and electron microscopy were also performed. Torn supraspinatus muscles had a 30% reduction in maximum isometric force production and a 29% reduction in normalized force compared with controls. Normalized supraspinatus fiber force positively correlated with ASES score and negatively correlated with tear size. Disordered sarcomeres were noted, along with an accumulation of lipid-laden macrophages in the extracellular matrix surrounding supraspinatus muscle fibers. Patients with chronic supraspinatus tears have significant reductions in muscle fiber force production. Force production also correlates with ASES scores and tear size. The structural and functional muscle dysfunction of the residual muscle fibers is independent of the additional area taken up by fibrotic tissue. This work may help establish future therapies to restore muscle function after the repair of chronically torn rotator cuff muscles. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  19. Influence of muscle fiber type composition on early fat accumulation under high-fat diet challenge.

    PubMed

    Hua, Ning; Takahashi, Hirokazu; Yee, Grace M; Kitajima, Yoichiro; Katagiri, Sayaka; Kojima, Motoyasu; Anzai, Keizo; Eguchi, Yuichiro; Hamilton, James A

    2017-01-01

    To investigate whether differences in muscle fiber types affect early-stage fat accumulation, under high fat diet challenge in mice. Twelve healthy male C57BL/6 mice experienced with short-term (6 weeks) diet treatment for the evaluation of early pattern changes in muscular fat. The mice were randomly divided into two groups: high fat diet (n = 8) and normal control diet (n = 4). Extra- and intra-myocellular lipid (EMCL and IMCL) in lumbar muscles (type I fiber predominant) and tibialis anterior (TA) muscle (type II fiber predominant) were determined using magnetic resonance spectroscopy (MRS). Correlation of EMCL, IMCL and their ratio between TA and lumbar muscles was evaluated. EMCL increased greatly in both muscle types after high fat diet. IMCL in TA and lumbar muscles increased to a much lower extent, with a slightly greater increase in TA muscles. EMCLs in the 2 muscles were positively correlated (r = 0.84, p = 0.01), but IMCLs showed a negative relationship (r = -0.84, p = 0.01). In lumbar muscles, high fat diet significantly decreased type I fiber while it increased type II fiber (all p≤0.001). In TA muscle, there was no significant fiber type shifting (p>0.05). Under short-time high fat diet challenge, lipid tends to initially accumulate extra-cellularly. In addition, compared to type II dominant muscle, Type I dominant muscle was less susceptible to IMCL accumulation but more to fiber type shifting. These phenomena might reflect compensative responses of skeletal muscle to dietary lipid overload in order to regulate metabolic homeostasis.

  20. Oxygen diffusion coefficient in isolated chicken red and white skeletal muscle fibers in ontogenesis.

    PubMed

    Baranov, V I; Belichenko, V M; Shoshenko, C A

    2000-09-01

    Oxygen diffusion from medium to cultured isolated muscle fibers from red gastrocnemius muscle (deep part) (RGM) and white pectoralis muscle (WPM) of embryonic and postnatal chickens (about 6 months) was explored. The intracellular effective O(2) diffusion coefficient (D(i)) in muscle fiber was calculated from a model of a cylindrical fiber with a uniform distribution of an oxygen sink based on these experimentally measured parameters: critical tension of O(2) (PO(2)) on the surface of a fiber, specific rate of O(2) consumption by a weight unit of muscle fibers (;VO(2)), and average diameter of muscle fibers. The results document the rapid hypertrophic growth of RGM fibers when compared to WPM fibers in the second half of the embryonic period and the higher values of;VO(2) and critical PO(2) during the ontogenetic period under study. The oxygen D(i) in RGM fibers of embryos and 1-day chickens was two to three times higher than observed for WPM fibers. For senior chickens, the oxygen D(i) value in RGM and WPM fibers does not differ. The D(i) of O(2) in both RGM and WPM fibers increased from 1.4-2.7 x 10(-8) to 90-95 x 10(-8) cm(2)/s with an ontogenetic increase in fiber diameter from 7. 5 to 67.0 microm. At all stages the oxygen D(i) values in RGM and WPM fibers are significantly lower than the O(2) diffusion coefficient in water: for 11-day embryos they are 889 and 1714 times lower and for adult individuals 25 and 27 times lower, respectively. Why oxygen D(i) values in RGM and WPM fibers are so low and why they are gradually increasing during the course of hypertrophic ontogenetic growth are still unclear. Copyright 2000 Academic Press.

  1. Fiber atrophy and hypertrophy in skeletal muscles of late middle-aged Fischer 344 x Brown Norway F1-hybrid rats.

    PubMed

    Hepple, Russell T; Ross, Karen D; Rempfer, Amanda B

    2004-02-01

    We examined young adult and late middle-aged male rats to test the hypothesis that gastrocnemius (a locomotor muscle) demonstrates reduced fiber size with aging, whereas soleus (a postural muscle) demonstrates atrophy of some fibers and compensatory hypertrophy in other fibers. Although body mass was greater in late middle-aged animals, mass was reduced in gastrocnemius but not soleus muscle. In another group of animals, physical activity was reduced by 34% in late middle-aged animals. Whereas mean fiber size was lower in gastrocnemius of late middle-aged animals, it was not different in soleus. Histograms revealed atrophied fibers (fibers (>/=8000 micro m(2)) in soleus with aging. Atrophied fibers often demonstrated no subsarcolemmal mitochondrial staining, suggesting denervation, whereas hypertrophied fibers often demonstrated cytochrome oxidase deficiency, suggesting mitochondrial dysfunction. These results underscore the divergent influences (e.g., physical inactivity, denervation, mitochondrial dysfunction) affecting fiber size with aging.

  2. Catalase-positive microperoxisomes in rat soleus and extensor digitorum longus muscle fiber types

    NASA Technical Reports Server (NTRS)

    Riley, Danny A.; Bain, James L. W.; Ellis, Stanley

    1988-01-01

    The size, distribution, and content of catalase-reactive microperoxisomes were investigated cytochemically in three types of muscle fibers from the soleus and the extensor digitorum longus (EDL) of male rats. Muscle fibers were classified on the basis of the mitochondrial content and distribution, the Z-band widths, and the size and shape of myofibrils as the slow-twitch oxidative (SO), the fast-twitch oxidative glycolytic (FOG), and the fast-twitch glycolytic (FG) fibers. It was found that both the EDL and soleus SO fibers possessed the largest microperoxisomes. A comparison of microperoxisome number per muscle fiber area or the microperoxisome area per fiber area revealed following ranking, starting from the largest number and the area-ratio values: soleus SO, EDL SO, EDL FOG, and EDL FG.

  3. Myonuclear Domain Flexibility Challenges Rigid Assumptions on Satellite Cell Contribution to Skeletal Muscle Fiber Hypertrophy.

    PubMed

    Murach, Kevin A; Englund, Davis A; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

    2018-01-01

    Satellite cell-mediated myonuclear accretion is thought to be required for skeletal muscle fiber hypertrophy, and even drive hypertrophy by preceding growth. Recent studies in humans and rodents provide evidence that challenge this axiom. Specifically, Type 2 muscle fibers reliably demonstrate a substantial capacity to hypertrophy in the absence of myonuclear accretion, challenging the notion of a tightly regulated myonuclear domain (i.e., area that each myonucleus transcriptionally governs). In fact, a "myonuclear domain ceiling", or upper limit of transcriptional output per nucleus to support hypertrophy, has yet to be identified. Satellite cells respond to muscle damage, and also play an important role in extracellular matrix remodeling during loading-induced hypertrophy. We postulate that robust satellite cell activation and proliferation in response to mechanical loading is largely for these purposes. Future work will aim to elucidate the mechanisms by which Type 2 fibers can hypertrophy without additional myonuclei, the extent to which Type 1 fibers can grow without myonuclear accretion, and whether a true myonuclear domain ceiling exists.

  4. Changes in Quadriceps Muscle Activity During Sustained Recreational Alpine Skiing

    PubMed Central

    Kröll, Josef; Müller, Erich; Seifert, John G.; Wakeling, James M.

    2011-01-01

    During a day of skiing thousands of repeated contractions take place. Previous research on prolonged recreational alpine skiing show that physiological changes occur and hence some level of fatigue is inevitable. In the present paper the effect of prolonged skiing on the recruitment and coordination of the muscle activity was investigated. Six subjects performed 24 standardized runs. Muscle activity during the first two (PREskiing) and the last two (POSTskiing) runs was measured from the vastus lateralis (VL) and rectus femoris (RF) using EMG and quantified using wavelet and principal component analysis. The frequency content of the EMG signal shifted in seven out of eight cases significantly towards lower frequencies with highest effects observed for RF on outside leg. A significant pronounced outside leg loading occurred during POSTskiing and the timing of muscle activity peaks occurred more towards turn completion. Specific EMG frequency changes were observed at certain time points throughout the time windows and not over the whole double turn. It is suggested that general muscular fatigue, where additional specific muscle fibers have to be recruited due to the reduced power output of other fibers did not occur. The EMG frequency decrease and intensity changes for RF and VL are caused by altered timing (coordination) within the turn towards a most likely more uncontrolled skiing technique. Hence, these data provide evidence to suggest recreational skiers alter their skiing technique before a potential change in muscle fiber recruitment occurs. Key points The frequency content of the EMG signal shifted in seven out of eight cases significantly towards lower frequencies with highest effects observed for RF. General muscular fatigue, where additional specific fibers have to be recruited due to the reduced power output of other fibers, did not occur. A modified skiing style towards a less functional and hence more uncontrolled skiing technique seems to be a key

  5. Fiber type-specific analysis of AMPK isoforms in human skeletal muscle: advancement in methods via capillary nanoimmunoassay.

    PubMed

    Tobias, Irene S; Lazauskas, Kara K; Arevalo, Jose A; Bagley, James R; Brown, Lee E; Galpin, Andrew J

    2018-04-01

    Human skeletal muscle is a heterogeneous mixture of multiple fiber types (FT). Unfortunately, present methods for FT-specific study are constrained by limits of protein detection in single-fiber samples. These limitations beget compensatory resource-intensive procedures, ultimately dissuading investigators from pursuing FT-specific research. Additionally, previous studies neglected hybrid FT, confining their analyses to only pure FT. Here we present novel methods of protein detection across a wider spectrum of human skeletal muscle FT using fully automated capillary nanoimmunoassay (CNIA) technology. CNIA allowed a ~20-fold-lower limit of 5'-AMP-activated protein kinase (AMPK) detection compared with Western blotting. We then performed FT-specific assessment of AMPK expression as a proof of concept. Individual human muscle fibers were mechanically isolated, dissolved, and myosin heavy chain (MHC) fiber typed via SDS-PAGE. Single-fiber samples were combined in pairs and grouped into MHC I, MHC I/IIa, MHC IIa, and MHC IIa/IIx for expression analysis of AMPK isoforms α 1 , α 2 , β 1 , β 2 , γ 2 , and γ 3 with a tubulin loading control. Significant FT-specific differences were found for α 2 (1.7-fold higher in MHC IIa and MHC IIa/IIx vs. others), γ 2 (2.5-fold higher in MHC IIa vs. others), and γ 3 (2-fold higher in MHC IIa and 4-fold higher in MHC IIa/IIx vs. others). Development of a protocol that combines the efficient and sensitive CNIA technology with comprehensive SDS-PAGE fiber typing marks an important advancement in FT-specific research because it allows more precise study of the molecular mechanisms governing metabolism, adaptation, and regulation in human muscle. NEW & NOTEWORTHY We demonstrate the viability of applying capillary nanoimmunoassay technology to the study of fiber type-specific protein analysis in human muscle fibers. This novel technique enables a ~20-fold-lower limit of protein detection compared with traditional Western blotting

  6. Jaw muscle fiber type distribution in Hawaiian gobioid stream fishes: histochemical correlations with feeding ecology and behavior.

    PubMed

    Maie, Takashi; Meister, Andrew B; Leonard, Gerald L; Schrank, Gordon D; Blob, Richard W; Schoenfuss, Heiko L

    2011-12-01

    Differences in fiber type distribution in the axial muscles of Hawaiian gobioid stream fishes have previously been linked to differences in locomotor performance, behavior, and diet across species. Using ATPase assays, we examined fiber types of the jaw opening sternohyoideus muscle across five species, as well as fiber types of three jaw closing muscles (adductor mandibulae A1, A2, and A3). The jaw muscles of some species of Hawaiian stream gobies contained substantial red fiber components. Some jaw muscles always had greater proportions of white muscle fibers than other jaw muscles, independent of species. In addition, comparing across species, the dietary generalists (Awaous guamensis and Stenogobius hawaiiensis) had a lower proportion of white muscle fibers in all jaw muscles than the dietary specialists (Lentipes concolor, Sicyopterus stimpsoni, and Eleotris sandwicensis). Among Hawaiian stream gobies, generalist diets may favor a wider range of muscle performance, provided by a mix of white and red muscle fibers, than is typical of dietary specialists, which may have a higher proportion of fast-twitch white fibers in jaw muscles to help meet the demands of rapid predatory strikes or feeding in fast-flowing habitats. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body myositis, regenerating and necrotic muscle fibers, and at neuromuscular junctions.

    PubMed

    Askanas, V; Engel, W K; Alvarez, R B; McFerrin, J; Broccolini, A

    2000-07-01

    Alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older patients. Its muscle phenotype shows several similarities with Alzheimer disease brain. A distinct feature of s-IBM pathology is specific vacuolar degeneration of muscle fibers characterized by intracellular amyloid inclusions formed by both amyloid-beta (Abeta) and paired-helical filaments composed of phosphorylated tau. We immunostained alpha-syn in muscle biopsies of s-IBM, disease-control, and normal patients. Approximately 60% of Abeta-positive vacuolated muscle fibers (VMF) contained well-defined inclusions immunoreactive with antibodies against alpha-syn. In those fibers. alpha-syn co-localized with Abeta, both by light microscopy, and ultrastructurally. Paired-helical filaments did not contain alpha-syn immunoreactivity. In all muscle biopsies, alpha-syn was strongly immunoreactive at the postsynaptic region of the neuromuscular junctions. alpha-syn immunoreactivity also occurred diffusely in regenerating and necrotic muscle fibers. In cultured human muscle fibers, alpha-syn and its mRNA were expressed by immunocytochemistry, immunoblots, and Northern blots. Our study provides the first demonstration that alpha-syn participates in normal and pathologic processes of human muscle. Therefore. its function is not exclusive to the brain and neurodegenerative diseases.

  8. Effects of pH on contraction of rabbit fast and slow skeletal muscle fibers.

    PubMed Central

    Chase, P B; Kushmerick, M J

    1988-01-01

    We have investigated (a) effects of varying proton concentration on force and shortening velocity of glycerinated muscle fibers, (b) differences between these effects on fibers from psoas (fast) and soleus (slow) muscles, possibly due to differences in the actomyosin ATPase kinetic cycles, and (c) whether changes in intracellular pH explain altered contractility typically associated with prolonged excitation of fast, glycolytic muscle. The pH range was chosen to cover the physiological pH range (6.0-7.5) as well as pH 8.0, which has often been used for in vitro measurements of myosin ATPase activity. Steady-state isometric force increased monotonically (by about threefold) as pH was increased from pH 6.0; force in soleus (slow) fibers was less affected by pH than in psoas (fast) fibers. For both fiber types, the velocity of unloaded shortening was maximum near resting intracellular pH in vivo and was decreased at acid pH (by about one-half). At pH 6.0, force increased when the pH buffer concentration was decreased from 100 mM, as predicted by inadequate pH buffering and pH heterogeneity in the fiber. This heterogeneity was modeled by net proton consumption within the fiber, due to production by the actomyosin ATPase coupled to consumption by the creatine kinase reaction, with replenishment by diffusion of protons in equilibrium with a mobile buffer. Lactate anion had little mechanical effect. Inorganic phosphate (15 mM total) had an additive effect of depressing force that was similar at pH 7.1 and 6.0. By directly affecting the actomyosin interaction, decreased pH is at least partly responsible for the observed decreases in force and velocity in stimulated muscle with sufficient glycolytic capacity to decrease pH. Images FIGURE 1 PMID:2969265

  9. The Drosophila indirect flight muscle myosin heavy chain isoform is insufficient to transform the jump muscle into a highly stretch-activated muscle type.

    PubMed

    Zhao, Cuiping; Swank, Douglas M

    2017-02-01

    Stretch activation (SA) is a delayed increase in force that enables high power and efficiency from a cyclically contracting muscle. SA exists in various degrees in almost all muscle types. In Drosophila, the indirect flight muscle (IFM) displays exceptionally high SA force production (F SA ), whereas the jump muscle produces only minimal F SA We previously found that expressing an embryonic (EMB) myosin heavy chain (MHC) isoform in the jump muscle transforms it into a moderately SA muscle type and enables positive cyclical power generation. To investigate whether variation in MHC isoforms is sufficient to produce even higher F SA , we substituted the IFM MHC isoform (IFI) into the jump muscle. Surprisingly, we found that IFI only caused a 1.7-fold increase in F SA , less than half the increase previously observed with EMB, and only at a high Pi concentration, 16 mM. This IFI-induced F SA is much less than what occurs in IFM, relative to isometric tension, and did not enable positive cyclical power generation by the jump muscle. Both isometric tension and F SA of control fibers decreased with increasing Pi concentration. However, for IFI-expressing fibers, only isometric tension decreased. The rate of F SA generation was ~1.5-fold faster for IFI fibers than control fibers, and both rates were Pi dependent. We conclude that MHC isoforms can alter F SA and hence cyclical power generation but that isoforms can only endow a muscle type with moderate F SA Highly SA muscle types, such as IFM, likely use a different or additional mechanism. Copyright © 2017 the American Physiological Society.

  10. Epaxial muscle fiber architecture favors enhanced excursion and power in the leaper Galago senegalensis

    PubMed Central

    Huq, Emranul; Wall, Christine E; Taylor, Andrea B

    2015-01-01

    Galago senegalensis is a habitual arboreal leaper that engages in rapid spinal extension during push-off. Large muscle excursions and high contraction velocities are important components of leaping, and experimental studies indicate that during leaping by G. senegalensis, peak power is facilitated by elastic storage of energy. To date, however, little is known about the functional relationship between epaxial muscle fiber architecture and locomotion in leaping primates. Here, fiber architecture of select epaxial muscles is compared between G. senegalensis (n = 4) and the slow arboreal quadruped, Nycticebus coucang (n = 4). The hypothesis is tested that G. senegalensis exhibits architectural features of the epaxial muscles that facilitate rapid and powerful spinal extension during the take-off phase of leaping. As predicted, G. senegalensis epaxial muscles have relatively longer, less pinnate fibers and higher ratios of tendon length-to-fiber length, indicating the capacity for generating relatively larger muscle excursions, higher whole-muscle contraction velocities, and a greater capacity for elastic energy storage. Thus, the relatively longer fibers and higher tendon length-to-fiber length ratios can be functionally linked to leaping performance in G. senegalensis. It is further predicted that G. senegalensis epaxial muscles have relatively smaller physiological cross-sectional areas (PCSAs) as a consequence of an architectural trade-off between fiber length (excursion) and PCSA (force). Contrary to this prediction, there are no species differences in relative PCSAs, but the smaller-bodied G. senegalensis trends towards relatively larger epaxial muscle mass. These findings suggest that relative increase in muscle mass in G. senegalensis is largely attributable to longer fibers. The relative increase in erector spinae muscle mass may facilitate sagittal flexibility during leaping. The similarity between species in relative PCSAs provides empirical support

  11. Calcium and stretch activation modulate power generation in Drosophila flight muscle.

    PubMed

    Wang, Qian; Zhao, Cuiping; Swank, Douglas M

    2011-11-02

    Many animals regulate power generation for locomotion by varying the number of muscle fibers used for movement. However, insects with asynchronous flight muscles may regulate the power required for flight by varying the calcium concentration ([Ca(2+)]). In vivo myoplasmic calcium levels in Drosophila flight muscle have been found to vary twofold during flight and to correlate with aerodynamic power generation and wing beat frequency. This mechanism can only be possible if [Ca(2+)] also modulates the flight muscle power output and muscle kinetics to match the aerodynamic requirements. We found that the in vitro power produced by skinned Drosophila asynchronous flight muscle fibers increased with increasing [Ca(2+)]. Positive muscle power generation started at pCa = 5.8 and reached its maximum at pCa = 5.25. A twofold variation in [Ca(2+)] over the steepest portion of this curve resulted in a two- to threefold variation in power generation and a 1.2-fold variation in speed, matching the aerodynamic requirements. To determine the mechanism behind the variation in power, we analyzed the tension response to muscle fiber-lengthening steps at varying levels of [Ca(2+)]. Both calcium-activated and stretch-activated tensions increased with increasing [Ca(2+)]. However, calcium tension saturated at slightly lower [Ca(2+)] than stretch-activated tension, such that as [Ca(2+)] increased from pCa = 5.7 to pCa = 5.4 (the range likely used during flight), stretch- and calcium-activated tension contributed 80% and 20%, respectively, to the total tension increase. This suggests that the response of stretch activation to [Ca(2+)] is the main mechanism by which power is varied during flight. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  12. Theory of the tensile actuation of fiber reinforced coiled muscles

    NASA Astrophysics Data System (ADS)

    Lamuta, C.; Messelot, S.; Tawfick, S.

    2018-05-01

    There is a strong need for compact artificial muscles capable of applying large contractile strokes and lift heavy weights. Coiled fibers recently emerged as attractive candidates for these purposes, owing to their simple construction and the possibility of their thermal, electrical and chemical actuation. An intuitive theoretical understanding of the mechanics of actuation of these muscles is essential for the enhancement of their performance and can pave the way for the development of new applications and technologies. In this paper, a complete theoretical model for the tensile actuation of fiber reinforced artificial muscles is presented and experimentally validated. The model demonstrates that all muscles made from the same material have a universal behavior, which can be described by a single master curve. It enables the systematic design and understanding of coiled muscles for specific performance owing to a comprehensive mathematical correlation among the geometry, materials properties, and actuation. Carbon fibers (CF)/polydimethylsiloxane coiled muscles are demonstrated as simple to fabricate yet powerful muscles owing to the availability of high strength CF. In addition to showing excellent agreement with the theoretical models, they can be actuated by joule heating or chemical swelling, lift up to 12 600 times their own weight, support up to 60 MPa of mechanical stress, provide tensile strokes higher than 25%, and a specific work up to 758 J kg‑1, the latter is more than 18 times higher than that of natural muscles.

  13. Effect of protons on the mechanical response of rat muscle nociceptive fibers and neurons in vitro.

    PubMed

    Hotta, Norio; Kubo, Asako; Mizumura, Kazue

    2015-03-01

    Strong exercise makes muscle acidic, and painful. The stimulus that activates muscle nociceptors in such instance may be protons. Reportedly, however, not many afferents are excited by protons alone. We, therefore, posited that protons sensitize muscular nociceptors to mechanical stimuli. We examined effects of protons on mechanical sensitivity of muscle nociceptors by single-fiber recording from rat muscle-nerve preparations in vitro and by whole cell patch-clamp recording of mechanically activated (MA) currents from cultured rat dorsal root ganglion neurons. We recorded 38 Aδ- and C-fibers. Their response magnitude was increased by both pH 6.2 and pH 6.8; in addition the mechanical threshold was lowered by pH 6.2. Decrease in the threshold by pH6.2 was also observed in MA currents. Presently observed sensitization by protons could be involved in several types of ischemic muscle pain, and may also be involved in cardiovascular and respiratory controls during exercise. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  14. Effect of oxotremorine on resting membrane potential and cell volume in skeletal muscle fibers in rats after in vivo blockade of NO-synthase.

    PubMed

    Khairova, R A; Malomuzh, A I; Naumenko, N V; Urazaev, A Kh

    2003-02-01

    Denervation of rat phrenic muscle or block of NO-synthase in vivo increased the cross-section area of muscle fibers and decreased membrane resting potential. Oxotremorine prevented the development of denervation-induced or denervation-like (i.e. induced by NO-synthase blockade) membrane depolarization and increase of the cross-sectional area of muscle fibers. Pirenzepine abolished the effects of oxotremorine. It was concluded that non-quantal acetylcholine can be involved in the regulation of skeletal muscle fiber volume via activation of M1 muscarinic receptors followed by NO synthesis.

  15. Calpain activity in fast, slow, transforming, and regenerating skeletal muscles of rat.

    PubMed

    Sultan, K R; Dittrich, B T; Pette, D

    2000-09-01

    Fiber-type transitions in adult skeletal muscle induced by chronic low-frequency stimulation (CLFS) encompass coordinated exchanges of myofibrillar protein isoforms. CLFS-induced elevations in cytosolic Ca(2+) could activate proteases, especially calpains, the major Ca(2+)-regulated cytosolic proteases. Calpain activity determined by a fluorogenic substrate in the presence of unaltered endogenous calpastatin activities increased twofold in low-frequency-stimulated extensor digitorum longus (EDL) muscle, reaching a level intermediate between normal fast- and slow-twitch muscles. micro- and m-calpains were delineated by a calpain-specific zymographical assay that assessed total activities independent of calpastatin and distinguished between native and processed calpains. Contrary to normal EDL, structure-bound, namely myofibrillar and microsomal calpains, were abundant in soleus muscle. However, the fast-to-slow conversion of EDL was accompanied by an early translocation of cytosolic micro-calpain, suggesting that myofibrillar and microsomal micro-calpain was responsible for the twofold increase in activity and thus involved in controlled proteolysis during fiber transformation. This is in contrast to muscle regeneration where m-calpain translocation predominated. Taken together, we suggest that translocation is an important step in the control of calpain activity in skeletal muscle in vivo.

  16. Systems Biology of Skeletal Muscle: Fiber Type as an Organizing Principle

    PubMed Central

    Greising, Sarah M; Gransee, Heather M; Mantilla, Carlos B; Sieck, Gary C

    2012-01-01

    Skeletal muscle force generation and contraction are fundamental to countless aspects of human life. The complexity of skeletal muscle physiology is simplified by fiber type classification where differences are observed from neuromuscular transmission to release of intracellular Ca2+ from the sarcoplasmic reticulum and the resulting recruitment and cycling of cross-bridges. This review uses fiber type classification as an organizing and simplifying principle to explore the complex interactions between the major proteins involved in muscle force generation and contraction. PMID:22811254

  17. Active behavior of abdominal wall muscles: Experimental results and numerical model formulation.

    PubMed

    Grasa, J; Sierra, M; Lauzeral, N; Muñoz, M J; Miana-Mena, F J; Calvo, B

    2016-08-01

    In the present study a computational finite element technique is proposed to simulate the mechanical response of muscles in the abdominal wall. This technique considers the active behavior of the tissue taking into account both collagen and muscle fiber directions. In an attempt to obtain the computational response as close as possible to real muscles, the parameters needed to adjust the mathematical formulation were determined from in vitro experimental tests. Experiments were conducted on male New Zealand White rabbits (2047±34g) and the active properties of three different muscles: Rectus Abdominis, External Oblique and multi-layered samples formed by three muscles (External Oblique, Internal Oblique, and Transversus Abdominis) were characterized. The parameters obtained for each muscle were incorporated into a finite strain formulation to simulate active behavior of muscles incorporating the anisotropy of the tissue. The results show the potential of the model to predict the anisotropic behavior of the tissue associated to fibers and how this influences on the strain, stress and generated force during an isometric contraction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Assessment of passive muscle elongation using Diffusion Tensor MRI: Correlation between fiber length and diffusion coefficients.

    PubMed

    Mazzoli, Valentina; Oudeman, Jos; Nicolay, Klaas; Maas, Mario; Verdonschot, Nico; Sprengers, Andre M; Nederveen, Aart J; Froeling, Martijn; Strijkers, Gustav J

    2016-12-01

    In this study we investigated the changes in fiber length and diffusion parameters as a consequence of passive lengthening and stretching of the calf muscles. We hypothesized that changes in radial diffusivity (RD) are caused by changes in the muscle fiber cross sectional area (CSA) as a consequence of lengthening and shortening of the muscle. Diffusion Tensor MRI (DT-MRI) measurements were made twice in five healthy volunteers, with the foot in three different positions (30° plantarflexion, neutral position and 15° dorsiflexion). The muscles of the calf were manually segmented on co-registered high resolution anatomical scans, and maps of RD and axial diffusivity (AD) were reconstructed from the DT-MRI data. Fiber tractography was performed and mean fiber length was calculated for each muscle group. Significant negative correlations were found between the changes in RD and changes in fiber length in the dorsiflexed and plantarflexed positions, compared with the neutral foot position. Changes in AD did not correlate with changes in fiber length. Assuming a simple cylindrical model with constant volume for the muscle fiber, the changes in the muscle fiber CSA were calculated from the changes in fiber length. In line with our hypothesis, we observed a significant positive correlation of the CSA with the measured changes in RD. In conclusion, we showed that changes in diffusion coefficients induced by passive muscle stretching and lengthening can be explained by changes in muscle CSA, advancing the physiological interpretation of parameters derived from skeletal muscle DT-MRI. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Effect of swim exercise training on human muscle fiber function

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Costill, D. L.; Gardetto, P. R.

    1989-01-01

    The effect of swim exercise training on the human muscle fiber function was investigated in swimmers trained in a typical collegiate swim-training program followed by an intensified 10-day training period. The measured parameters included the peak tension (P0), negative log molar Ca(2+) concentration (pCa)-force, and maximal shortening speed (Vmax) of the slow-twitch type I and fast-twitch type II fibers obtained by biopsy from the deltoid muscle. The P0 values were found to be not altered after either the training or the 10-day intensive program. The type I fibers from the trained swimmers showed pCa-force curves shifted to the right, such that higher free Ca(2+) levels were required to elicit a given percent of P0. The training program significantly increased the Vmax in the type I fibers and decreased that of the type II fibers, and the 10-day intensive training produced a further significant decrease of the type II fibers.

  20. Viscous dietary fiber reduces adiposity and plasma leptin and increases muscle expression of fat oxidation genes in rats.

    PubMed

    Islam, Ajmila; Civitarese, Anthony E; Hesslink, Robert L; Gallaher, Daniel D

    2012-02-01

    Dietary interventions that reduce accumulation of body fat are of great interest. Consumption of viscous dietary fibers cause well-known positive metabolic effects, such as reductions in the postprandial glucose and insulin concentrations. However, their effect on body composition and fuel utilization has not been previously studied. To examine this, rats were fed a viscous nonfermentable dietary fiber, hydroxypropyl methylcellulose (HPMC), for 6 weeks. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and fat pad weight. Plasma adipokines, AMP kinase activation, and enzyme and mRNA analysis of key regulators of energetics in liver and soleus muscle were measured. The HPMC diet significantly lowered percent body fat mass and increased percent lean body mass, compared to a cellulose-containing diet (no viscosity). Fasting leptin was reduced 42% and resistin 28% in the HPMC group compared to the cellulose group. Rats fed HPMC had greater activation of AMP kinase in liver and muscle and lower phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. mRNA expression in skeletal muscle was significantly increased for carnitine palmitoyltransferase 1B (CPT-1B), PPARγ coactivator 1α, PPARδ and uncoupling protein 3 (UCP3), as was citrate synthase (CS) activity, in the HPMC group relative to the cellulose group. These results indicate that viscous dietary fiber preserves lean body mass and reduces adiposity, possibly by increasing mitochondrial biogenesis and fatty acid oxidation in skeletal muscle, and thus represents a metabolic effect of viscous fiber not previously described. Thus, viscous dietary fiber may be a useful dietary component to assist in reduction of body fat.

  1. Digital PCR Quantitation of Muscle Mitochondrial DNA: Age, Fiber Type, and Mutation-Induced Changes.

    PubMed

    Herbst, Allen; Widjaja, Kevin; Nguy, Beatrice; Lushaj, Entela B; Moore, Timothy M; Hevener, Andrea L; McKenzie, Debbie; Aiken, Judd M; Wanagat, Jonathan

    2017-10-01

    Definitive quantitation of mitochondrial DNA (mtDNA) and mtDNA deletion mutation abundances would help clarify the role of mtDNA instability in aging. To more accurately quantify mtDNA, we applied the emerging technique of digital polymerase chain reaction to individual muscle fibers and muscle homogenates from aged rodents. Individual fiber mtDNA content correlated with fiber type and decreased with age. We adapted a digital polymerase chain reaction deletion assay that was accurate in mixing experiments to a mutation frequency of 0.03% and quantitated an age-induced increase in deletion frequency from rat muscle homogenates. Importantly, the deletion frequency measured in muscle homogenates strongly correlated with electron transport chain-deficient fiber abundance determined by histochemical analyses. These data clarify the temporal accumulation of mtDNA deletions that lead to electron chain-deficient fibers, a process culminating in muscle fiber loss. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Muscle fiber characteristics of broiler breast fillets with the wooden breast condition.

    USDA-ARS?s Scientific Manuscript database

    Broiler breast fillets exhibiting the wooden breast condition are described as having a rigid feel and abnormal texture attributes; however, changes at the muscle fiber level in wooden breast fillets are not well understood. The objective of this study was to compare the histochemical muscle fiber ...

  3. Extensibility of the myofilaments in vertebrate skeletal muscle as revealed by stretching rigor muscle fibers

    PubMed Central

    1983-01-01

    The extensibility of the myofilaments in vertebrate skeletal muscle was studied by stretching glycerinated rabbit psoas muscle fibers in rigor state and examining the resulting extension of sarcomere structures under an electron microscope. Although stretches applied to rigor fibers produced a successive yielding of the weakest sarcomeres, the length of the remaining intact sarcomeres in many myofibrils was fairly uniform, being definitely longer than the sarcomeres in the control, nonstretched part of rigor fibers. The stretch-induced increase in sarcomere length was found to be taken up by the extension of the H zone and the I band, whereas the amount of overlap between the thick and thin filaments did not change appreciably with stretches of 10-20%. The thick filament extension in the H zone was localized in the bare regions, whereas the thin filament extension in the I band appeared to take place uniformly along the filament length. No marked increase in the Z-line width was observed even with stretches of 20-30%. These results clearly demonstrate the extensibility of the thick and thin filaments. The possible contribution of the myofilament compliance to the series elastic component (SEC) in vertebrate skeletal muscle fibers is discussed on the basis of the electron microscopic data and the force-extension curve of the SEC in rigor fibers. PMID:6682885

  4. Light diffraction studies of single muscle fibers as a function of fiber rotation.

    PubMed Central

    Gilliar, W G; Bickel, W S; Bailey, W F

    1984-01-01

    Light diffraction patterns from single glycerinated frog semitendinosus muscle fibers were examined photographically and photoelectrically as a function of diffraction angle and fiber rotation. The total intensity diffraction pattern indicates that the order maxima change both position and intensity periodically as a function of rotation angle. The total diffracted light, light diffracted above and below the zero-order plane, and light diffracted into individual orders gives information about the fiber's longitudinal and rotational structure and its noncylindrical symmetry. Images FIGURE 2 PMID:6611174

  5. Size and myonuclear domains in Rhesus soleus muscle fibers: short-term spaceflight

    NASA Technical Reports Server (NTRS)

    Roy, R. R.; Zhong, H.; Talmadge, R. J.; Bodine, S. C.; Fanton, J. W.; Koslovskaya, I.; Edgerton, V. R.

    2001-01-01

    The cross-sectional area (CSA), myonuclear number per mm of fiber length, and myonuclear domain (cytoplasmic volume/myonucleus) of mechanically isolated single fibers from biopsies of the soleus muscle of 5 vivarium control, 3 flight simulation and 2 flight (BION 11) Rhesus monkeys (Macaca [correction of Macacca] mulatta) were determined using confocal microscopy before and after a 14-day experimental period. Simulation monkeys were confined in chairs placed in capsules identical to those used during the flight. Fibers were classified as type I, type II or hybrid (containing both types I and II) based on myosin heavy chain (MHC) gel electrophoresis. A majority of the fibers sampled contained only type I MHC, i.e. 89, 62 and 68% for the control, simulation and flight groups, respectively. Most of the remaining fibers were hybrids, i.e. 8, 36 and 32% for the same groups. There were no significant pre-post differences in the fiber type composition for any of the experimental groups. There also were no significant pre-post differences in fiber CSA, myonuclear number or myonuclear domain. There was, however, a tendency for the fibers in the post-flight biopsies to have a smaller mean CSA and myonuclear domain (approximately 10%, p=0.07) than the fibers in the pre-flight biopsy. The combined mean cytoplasmic volume/myonucleus for all muscle fiber phenotypes in the Rhesus soleus muscle was approximately 25,000 micrometers3 and there were no differences in pre-post samples for the control and simulated groups. The cytoplasmic domains tended to be lower (p=0.08) after than before flight. No phenotype differences in cytoplasmic domains were observed. These data suggest that after a relatively short period of actual spaceflight, modest fiber atrophy occurs in the soleus muscle fibers without a concomitant change in myonuclear number.

  6. Development of medial pterygoid muscle fibers in rabbits fed with a liquid diet.

    PubMed

    Kuroki, Kozue; Morita, Takumi; Takasu, Hiroki; Saito, Keisuke; Fujiwara, Takuya; Hiraba, Katsunari; Goto, Shigemi

    2017-08-01

    This study aimed to investigate the influence of decreased functional load on the medial pterygoid muscle during mastication in rabbits fed with a liquid-diet. Medial pterygoid muscles from 54 rabbits (solid- and liquid-diet groups, n=48; unweaned group, n=6) were histochemically examined at 4, 9, 12, 18, and 33 weeks after birth. Six fiber types (I, IC, IIC, IIA, IIAB, and IIB) were distinguished via mATPase staining. Significant increases in the diameters of all fiber types were seen up to 33 weeks of age in the solid-diet group; however, no significant increase was noted in fiber types I and IC, from 4 to 33 weeks of age, in the liquid-diet group. The proportion of slow fibers increased up to 12 weeks followed by an increase in the number of fast fibers in the solid-diet group, whereas in the liquid-diet group, the number of slow fiber declined after weaning. Liquid-diet consumption caused muscle fiber atrophy and an increase in the number of fast fibers during early developmental stages after weaning. Furthermore, the growth pattern of the medial pterygoid muscle in the liquid-diet group was different from that in the solid-diet group. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Jaw-muscle fiber architecture in tufted capuchins favors generating relatively large muscle forces without compromising jaw gape.

    PubMed

    Taylor, Andrea B; Vinyard, Christopher J

    2009-12-01

    Tufted capuchins (sensu lato) are renowned for their dietary flexibility and capacity to exploit hard and tough objects. Cebus apella differs from other capuchins in displaying a suite of craniodental features that have been functionally and adaptively linked to their feeding behavior, particularly the generation and dissipation of relatively large jaw forces. We compared fiber architecture of the masseter and temporalis muscles between C. apella (n=12) and two "untufted" capuchins (C. capucinus, n=3; C. albifrons, n=5). These three species share broadly similar diets, but tufted capuchins occasionally exploit mechanically challenging tissues. We tested the hypothesis that tufted capuchins exhibit architectural properties of their jaw muscles that facilitate relatively large forces including relatively greater physiologic cross-sectional areas (PCSA), more pinnate fibers, and lower ratios of mass to tetanic tension (Mass/P(0)). Results show some evidence supporting these predictions, as C. apella has relatively greater superficial masseter and temporalis PCSAs, significantly so only for the temporalis following Bonferroni adjustment. Capuchins did not differ in pinnation angle or Mass/P(0). As an architectural trade-off between maximizing muscle force and muscle excursion/contraction velocity, we also tested the hypothesis that C. apella exhibits relatively shorter muscle fibers. Contrary to our prediction, there are no significant differences in relative fiber lengths between tufted and untufted capuchins. Therefore, we attribute the relatively greater PCSAs in tufted capuchins primarily to their larger muscle masses. These findings suggest that relatively large jaw-muscle PCSAs can be added to the suite of masticatory features that have been functionally linked to the exploitation of a more resistant diet by C. apella. By enlarging jaw-muscle mass to increase PCSA, rather than reducing fiber lengths and increasing pinnation, tufted capuchins appear to have

  8. Muscle contraction is required to maintain the pool of muscle progenitors via YAP and NOTCH during fetal myogenesis.

    PubMed

    Esteves de Lima, Joana; Bonnin, Marie-Ange; Birchmeier, Carmen; Duprez, Delphine

    2016-08-24

    The importance of mechanical activity in the regulation of muscle progenitors during chick development has not been investigated. We show that immobilization decreases NOTCH activity and mimics a NOTCH loss-of-function phenotype, a reduction in the number of muscle progenitors and increased differentiation. Ligand-induced NOTCH activation prevents the reduction of muscle progenitors and the increase of differentiation upon immobilization. Inhibition of NOTCH ligand activity in muscle fibers suffices to reduce the progenitor pool. Furthermore, immobilization reduces the activity of the transcriptional co-activator YAP and the expression of the NOTCH ligand JAG2 in muscle fibers. YAP forced-activity in muscle fibers prevents the decrease of JAG2 expression and the number of PAX7+ cells in immobilization conditions. Our results identify a novel mechanism acting downstream of muscle contraction, where YAP activates JAG2 expression in muscle fibers, which in turn regulates the pool of fetal muscle progenitors via NOTCH in a non-cell-autonomous manner.

  9. Artificial muscles made of chiral two-way shape memory polymer fibers

    NASA Astrophysics Data System (ADS)

    Yang, Qianxi; Fan, Jizhou; Li, Guoqiang

    2016-10-01

    In this work, we demonstrate the unusual improvement of the tensile actuation of hierarchically chiral structured artificial muscle made of two-way shape memory polymer (2W-SMP) fiber. Experimental results show that the chemically cross-linked poly(ethylene-co-vinyl acetate) 2W-SMP fibers possess an average negative coefficient of thermal expansion (NCTE) that is at least one order higher than that of the polyethylene fiber used previously. As expected, the increase in axial thermal contraction of the precursor fiber leads to an increase in the recovered torque ( 4.4 Nmm ) of the chiral fiber and eventually in the tensile actuation of the twisted-then-coiled artificial muscle ( 67.81 ±1.82 % ). A mechanical model based on Castigliano's second theorem is proposed, and the calculated result is consistent with the experimental result (64.17% tensile stroke). The model proves the significance of the NCTE and the recovered torque on tensile actuation of the artificial muscle and can be used as a guidance for the future design.

  10. A One-Step Immunostaining Method to Visualize Rodent Muscle Fiber Type within a Single Specimen

    PubMed Central

    Sawano, Shoko; Komiya, Yusuke; Ichitsubo, Riho; Ohkawa, Yasuyuki; Nakamura, Mako; Tatsumi, Ryuichi; Ikeuchi, Yoshihide; Mizunoya, Wataru

    2016-01-01

    In this study, we present a quadruple immunostaining method for rapid muscle fiber typing of mice and rats using antibodies specific to the adult myosin heavy chain (MyHC) isoforms MyHC1, 2A, 2X, and 2B, which are common marker proteins of distinct muscle fiber types. We developed rat monoclonal antibodies specific to each MyHC isoform and conjugated these four antibodies to fluorophores with distinct excitation and emission wavelengths. By mixing the four types of conjugated antibodies, MyHC1, 2A, 2X, and 2B could be distinguished within a single specimen allowing for facile delineation of skeletal muscle fiber types. Furthermore, we could observe hybrid fibers expressing MyHC2X and MyHC2B together in single longitudinal muscle sections from mice and rats, that was not attained in previous techniques. This staining method is expected to be applied to study muscle fiber type transition in response to environmental factors, and to ultimately develop techniques to regulate animal muscle fiber types. PMID:27814384

  11. Nandrolone normalizes determinants of muscle mass and fiber type after spinal cord injury.

    PubMed

    Wu, Yong; Zhao, Jingbo; Zhao, Weidong; Pan, Jiangping; Bauman, William A; Cardozo, Christopher P

    2012-05-20

    Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1α protein and PGC-1α mRNA levels. For PGC-1α target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1α in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1α target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation.

  12. Quadriceps muscle strength and voluntary activation after polio.

    PubMed

    Beelen, Anita; Nollet, Frans; de Visser, Marianne; de Jong, Bareld A; Lankhorst, Gustaaf J; Sargeant, Anthony J

    2003-08-01

    Quadriceps strength, maximal anatomical cross-sectional area (CSA), maximal voluntary activation (MVA), and maximal relaxation rate (MRR) were studied in 48 subjects with a past history of polio, 26 with and 22 without postpoliomyelitis syndrome (PPS), and in 13 control subjects. It was also investigated whether, apart from CSA, MVA and MRR were determinants of muscle strength. Polio subjects had significantly less strength, CSA, and MRR in the more-affected quadriceps than control subjects. MVA was reduced in 18 polio subjects and normal in all controls. PPS subjects differed from non-PPS subjects only in that the MVA of the more-affected quadriceps was significantly lower. Both CSA and MVA were found to be associated with muscle strength. Quadriceps strength in polio subjects was dependent not only on muscle mass, but also on the ability to activate the muscles. Since impaired activation was more pronounced in PPS subjects, the new muscle weakness and functional decline in PPS may be due not only to a gradual loss of muscle fibers, but also to an increasing inability to activate the muscles.

  13. Molecular determinants of force production in human skeletal muscle fibers: effects of myosin isoform expression and cross-sectional area.

    PubMed

    Miller, Mark S; Bedrin, Nicholas G; Ades, Philip A; Palmer, Bradley M; Toth, Michael J

    2015-03-15

    Skeletal muscle contractile performance is governed by the properties of its constituent fibers, which are, in turn, determined by the molecular interactions of the myofilament proteins. To define the molecular determinants of contractile function in humans, we measured myofilament mechanics during maximal Ca(2+)-activated and passive isometric conditions in single muscle fibers with homogenous (I and IIA) and mixed (I/IIA and IIA/X) myosin heavy chain (MHC) isoforms from healthy, young adult male (n = 5) and female (n = 7) volunteers. Fibers containing only MHC II isoforms (IIA and IIA/X) produced higher maximal Ca(2+)-activated forces over the range of cross-sectional areas (CSAs) examined than MHC I fibers, resulting in higher (24-42%) specific forces. The number and/or stiffness of the strongly bound myosin-actin cross bridges increased in the higher force-producing MHC II isoforms and, in all isoforms, better predicted force than CSA. In men and women, cross-bridge kinetics, in terms of myosin attachment time and rate of myosin force production, were independent of CSA, although women had faster (7-15%) kinetics. The relative proportion of cross bridges and/or their stiffness was reduced as fiber size increased, causing a decline in specific force. Results from our examination of molecular mechanisms across the range of physiological CSAs explain the variation in specific force among the different fiber types in human skeletal muscle, which may have relevance to understanding how various physiological and pathophysiological conditions modulate single-fiber and whole muscle contractility. Copyright © 2015 the American Physiological Society.

  14. Molecular determinants of force production in human skeletal muscle fibers: effects of myosin isoform expression and cross-sectional area

    PubMed Central

    Bedrin, Nicholas G.; Ades, Philip A.; Palmer, Bradley M.; Toth, Michael J.

    2015-01-01

    Skeletal muscle contractile performance is governed by the properties of its constituent fibers, which are, in turn, determined by the molecular interactions of the myofilament proteins. To define the molecular determinants of contractile function in humans, we measured myofilament mechanics during maximal Ca2+-activated and passive isometric conditions in single muscle fibers with homogenous (I and IIA) and mixed (I/IIA and IIA/X) myosin heavy chain (MHC) isoforms from healthy, young adult male (n = 5) and female (n = 7) volunteers. Fibers containing only MHC II isoforms (IIA and IIA/X) produced higher maximal Ca2+-activated forces over the range of cross-sectional areas (CSAs) examined than MHC I fibers, resulting in higher (24–42%) specific forces. The number and/or stiffness of the strongly bound myosin-actin cross bridges increased in the higher force-producing MHC II isoforms and, in all isoforms, better predicted force than CSA. In men and women, cross-bridge kinetics, in terms of myosin attachment time and rate of myosin force production, were independent of CSA, although women had faster (7–15%) kinetics. The relative proportion of cross bridges and/or their stiffness was reduced as fiber size increased, causing a decline in specific force. Results from our examination of molecular mechanisms across the range of physiological CSAs explain the variation in specific force among the different fiber types in human skeletal muscle, which may have relevance to understanding how various physiological and pathophysiological conditions modulate single-fiber and whole muscle contractility. PMID:25567808

  15. Analysis of muscle fiber conduction velocity during finger flexion and extension after stroke.

    PubMed

    Conrad, Megan O; Qiu, Dan; Hoffmann, Gilles; Zhou, Ping; Kamper, Derek G

    2017-05-01

    Stroke survivors experience greater strength deficits during finger extension than finger flexion. Prior research indicates relatively little observed weakness is directly attributable to muscle atrophy. Changes in other muscle properties, however, may contribute to strength deficits. This study measured muscle fiber conduction velocity (MFCV) in a finger flexor and extensor muscle to infer changes in muscle fiber-type after stroke. Conduction velocity was measured using a linear EMG surface electrode array for both extensor digitorum communis and flexor digitorum superficialis in 12 stroke survivors with chronic hand hemiparesis and five control subjects. Measurements were made in both hands for all subjects. Stroke survivors had either severe (n = 5) or moderate (n = 7) hand impairment. Absolute MFCV was significantly lower in the paretic hand of severely impaired stroke patients compared to moderately impaired patients and healthy control subjects. The relative MFCV between the two hands, however, was quite similar for flexor muscles across all subjects and for extensor muscles for the neurologically intact control subjects. However, MFCV for finger extensors was smaller in the paretic as compared to the nonparetic hand for both groups of stroke survivors. One explanation for reduced MFCV may be a type-II to type-I muscle fiber, especially in extrinsic extensors. Clinically, therapists may use this information to develop therapeutic exercises targeting loss of type-II fiber in extensor muscles.

  16. Dynamic formation of microenvironments at the myotendinous junction correlates with muscle fiber morphogenesis in zebrafish

    PubMed Central

    Snow, Chelsi J.; Henry, Clarissa A.

    2009-01-01

    Muscle development involves the specification and morphogenesis of muscle fibers that attach to tendons. After attachment, muscles and tendons then function as an integrated unit to transduce force to the skeletal system and stabilize joints. The attachment site is the myotendinous junction, or MTJ, and is the primary site of force transmission. We find that attachment of fast-twitch myofibers to the MTJ correlates with the formation of novel microenvironments within the MTJ. The expression or activation of two proteins involved in anchoring the intracellular cytoskeleton to the extracellular matrix, Focal adhesion kinase (Fak) and β-dystroglycan is up-regulated. Conversely, the extracellular matrix protein Fibronectin (Fn) is down-regulated. This degradation of Fn as fast-twitch fibers attach to the MTJ results in Fn protein defining a novel microenvironment within the MTJ adjacent to slow-twitch, but not fast-twitch, muscle. Interestingly, however, Fak, laminin, Fn and β-dystroglycan concentrate at the MTJ in mutants that do not have slow-twitch fibers. Taken together, these data elucidate novel and dynamic microenvironments within the MTJ and indicate that MTJ morphogenesis is spatially and temporally complex. PMID:18783736

  17. Using vertebral movement and intact paraspinal muscles to determine the distribution of intrafusal fiber innervation of muscle spindle afferents in the anesthetized cat.

    PubMed

    Reed, William R; Cao, Dong-Yuan; Ge, Weiqing; Pickar, Joel G

    2013-03-01

    Increasing our knowledge regarding intrafusal fiber distribution and physiology of paraspinal proprioceptors may provide key insights regarding proprioceptive deficits in trunk control associated with low back pain and lead to more effective clinical intervention. The use of vertebral movement as a means to reliably stretch paraspinal muscles would greatly facilitate physiological study of paraspinal muscle proprioceptors where muscle tendon isolation is either very difficult or impossible. The effects of succinylcholine (SCh) on 194 muscle spindle afferents from lumbar longissimus or multifidus muscles in response to computer-controlled, ramp-and-hold movements of the L(6) vertebra were investigated in anesthetized cats. Paraspinal muscles were stretched by moving the L(6) vertebra 1.5-1.7 mm in the dorsal-ventral direction. Initial frequency (IF), dynamic difference (DD), their changes (∆) following SCh injection (100-400 μg kg(-1)), and post-SCh dynamic difference (SChDD) were measured. Muscle spindle intrafusal fiber terminations were classified as primary or secondary fibers as well as bag(1) (b(1)c), bag(2) (b(2)c), b(1)b(2)c, or chain (c) fibers. Intrafusal fiber subpopulations were distinguished using logarithmic transformation of SChDD and ∆IF distributions as established by previous investigators. Increases in DD indicate strength of b(1)c influence while increases in IF indicate strength of b(2)c influence. Out of 194 afferents, 46.9 % of afferents terminated on b(2)c fibers, 46.4 % on b(1)b(2)c fibers, 1 % on b(1)c fibers, and 5.7 % terminated on c fibers. Based on these intrafusal fiber subpopulation distributions, controlled vertebral movement can effectively substitute for direct tendon stretch and allow further investigation of paraspinal proprioceptors in this anatomically complex body region.

  18. Differential MMP-2 and MMP-9 activity and collagen distribution in skeletal muscle from pacu (Piaractus mesopotamicus) during juvenile and adult growth phases.

    PubMed

    Michelin, Aline Cristina; Justulin, Luis Antonio; Delella, Flávia Karina; Padovani, Carlos Roberto; Felisbino, Sérgio Luis; Dal-Pai-Silva, Maeli

    2009-03-01

    Here, we evaluated collagen distribution and matrix metalloproteinases (MMPs) MMP-2 and MMP-9 activities in skeletal muscle of pacu (Piaractus mesopotamicus) during juvenile and adult growth phases. Muscle samples from juvenile and adult fishes were processed by histochemistry for collagen system fibers and for gelatin-zymography for MMP-2 and MMP-9 activities analysis. Picrosirius staining revealed a myosept, endomysium, and perimysium-like structures in both growth phases and muscle types, with increased areas of collagen fibers in adults, mainly in red muscle. Reticulin staining showed that reticular fibers in the endomysium-like structure were thinner and discontinuous in the red muscle fibers. The zymography revealed clear bands of the pro- MMP-9, active- MMP-9, intermediate- MMP-2, and active- MMP-2 forms in red and white muscle in both growth phases. MMP-2 activity was more intense in juvenile than adult muscle fibers. Comparing the red and white muscle types, MMP-2 activity was significantly higher in red muscle in adult phase only. The activity of MMP-9 forms was similar in juvenile red and white muscles and in the adult red muscle, without any activity in adult white muscle. In conclusion, our results show that, in pacu, the higher activities of MMP-2 and -9 are associated with the rapid muscle growth in juvenile age and in adult fish, these activities are related with a different red and white muscle physiology. This study may contribute to the understanding muscle growth mechanisms and may also contribute to analyse red and the white muscle parameters of firmness and softness, respectively, of the commercial product. (c) 2009 Wiley-Liss, Inc.

  19. Fiber-type composition in the perivertebral musculature of lizards: Implications for the evolution of the diapsid trunk muscles.

    PubMed

    Moritz, Sabine; Schilling, Nadja

    2013-03-01

    The perivertebral musculature of lizards is critical for the stabilization and the mobilization of the trunk during locomotion. Some trunk muscles are also involved in ventilation. This dual function of trunk muscles in locomotion and ventilation leads to a biomechanical conflict in many lizards and constrains their ability to breathe while running ("axial constraint") which likely is reflected by their high anaerobic scope. Furthermore, different foraging and predator-escape strategies were shown to correlate with the metabolic profile of locomotor muscles in lizards. Because knowledge of muscle's fiber-type composition may help to reveal a muscle's functional properties, we investigated the distribution pattern of muscle fiber types in the perivertebral musculature in two small lizard species with a generalized body shape and subjected to the axial constraint (Dipsosaurus dorsalis, Acanthodactylus maculatus) and one species that circumvents the axial constraint by means of gular pumping (Varanus exanthematicus). Additionally, these species differ in their predator-escape and foraging behaviors. Using refined enzyme-histochemical protocols, muscle fiber types were differentiated in serial cross-sections through the trunk, maintaining the anatomical relationships between the skeleton and the musculature. The fiber composition in Dipsosaurus and Acanthodactylus showed a highly glycolytic profile, consistent with their intermittent locomotor style and reliance on anaerobic metabolism during activity. Because early representatives of diapsids resemble these two species in several postcranial characters, we suggest that this glycolytic profile represents the plesiomorphic condition for diapsids. In Varanus, we found a high proportion of oxidative fibers in all muscles, which is in accordance with its high aerobic scope and capability of sustained locomotion. Copyright © 2012 Wiley Periodicals, Inc.

  20. Ultrastructural alterations in skeletal muscle fibers of rats after exercise

    NASA Technical Reports Server (NTRS)

    Akuzawa, M.; Hataya, M.

    1982-01-01

    Ultrastructural alterations in skeletal muscle fibers were electron microscopically studied in rats forced to run on the treadmill until all-out. When they were mild and limited to relatively small areas, the reconstruction of filaments ensued within 10 days without infiltration of cells. When they were severe and extensive, phagocytes infiltrated in the lesions and removed degenerative sacroplasmic debris from muscle fibers. A little later, myoblasts appeared and regeneration was accomplished in 30 days in much the same manner as in myogenesis.

  1. Early changes in fiber profile and capillary density in long-term stimulated muscles.

    PubMed

    Hudlická, O; Dodd, L; Renkin, E M; Gray, S D

    1982-10-01

    Predominantly fast skeletal muscles of rabbits [tibialis anterior (TA), extensor digitorum longus (EDL)] were stimulated at a frequency naturally occurring in nerves to slow muscles (10 Hz continuously) for 8 h/day for 2--4 days. Such stimulation is known to convert all glycolytic fibers to oxidative and to increase capillary density. Our aim was to study early stages of conversion to investigate the factors responsible for the changes. Staining of quick-frozen sections for myosin ATPase, succinic dehydrogenase, and alkaline phosphatase was used to study the distribution of different fiber types and to measure fiber cross-sectional areas, capillaries per square millimeter, and capillary-to-fiber ratios in each fiber category. TA but not EDL showed conversion of fast glycolytic to fast oxidative fibers after 2 days, more after 4 days of stimulation. In both muscles, the largest fast glycolytic fibers were diminished in number after stimulation. There was significant increase in total capillaries per square millimeter after 4 days and some increase after 2 days of stimulation. The increase in capillaries per square millimeter exceeded the increase in the number of fibers per square millimeter, and since there was no change in mean fiber area, the increase is attributed to capillary growth. In EDL, there was an increase in the number of capillaries supplying both fast glycolytic and fast oxidative fibers, suggesting that capillary growth precedes fiber type conversion. In TA, the number of capillaries supplying fast oxidative fibers was increased but that to fast glycolytic fibers, was not. This is consistent with capillary growth simultaneous with or following fiber conversion. In both TA and EDL the number of capillaries perfused after contraction was higher in stimulated muscles, suggesting that increased capillary flow contributed to capillary growth.

  2. Velocity, force, power, and Ca2+ sensitivity of fast and slow monkey skeletal muscle fibers

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Bodine, S. C.; Romatowski, J. G.; Widrick, J. J.

    1998-01-01

    In this study, we determined the contractile properties of single chemically skinned fibers prepared from the medial gastrocnemius (MG) and soleus (Sol) muscles of adult male rhesus monkeys and assessed the effects of the spaceflight living facility known as the experiment support primate facility (ESOP). Muscle biopsies were obtained 4 wk before and immediately after an 18-day ESOP sit, and fiber type was determined by immunohistochemical techniques. The MG slow type I fiber was significantly smaller than the MG type II, Sol type I, and Sol type II fibers. The ESOP sit caused a significant reduction in the diameter of type I and type I/II (hybrid) fibers of Sol and MG type II and hybrid fibers but no shift in fiber type distribution. Single-fiber peak force (mN and kN/m2) was similar between fiber types and was not significantly different from values previously reported for other species. The ESOP sit significantly reduced the force (mN) of Sol type I and MG type II fibers. This decline was entirely explained by the atrophy of these fiber types because the force per cross-sectional area (kN/m2) was not altered. Peak power of Sol and MG fast type II fiber was 5 and 8.5 times that of slow type I fiber, respectively. The ESOP sit reduced peak power by 25 and 18% in Sol type I and MG type II fibers, respectively, and, for the former fiber type, shifted the force-pCa relationship to the right, increasing the Ca2+ activation threshold and the free Ca2+ concentration, eliciting half-maximal activation. The ESOP sit had no effect on the maximal shortening velocity (Vo) of any fiber type. Vo of the hybrid fibers was only slightly higher than that of slow type I fibers. This result supports the hypothesis that in hybrid fibers the slow myosin heavy chain would be expected to have a disproportionately greater influence on Vo.

  3. Experiment K-308: Automatic analysis of muscle fibers from rats subjected to spaceflight

    NASA Technical Reports Server (NTRS)

    Castleman, K. R.; Chui, L. A.; Vandermeullen, J. P.

    1981-01-01

    The morphology of histochemically prepared muscle sections from the gastrocnemius and plantaris muscles of flight and vivarium control rats was studied quantitatively. Both fast-twitch and slow-twitch fibers were significantly smaller in flight groups than in control groups. Fibers in group 4F were somewhat larger than in 1F, presumably due to growth after recovery. Fibers in 4V were slightly larger than in 1V, presumably due to age. The slow fibers showed more spaceflight induced size loss than fast fibers, suggesting they suffered more from hypogravity. The proportion of slow fibers was also lower in the flight groups, suggesting spaceflight induced fiber type conversion from slow to fast.

  4. Constant Fiber Number During Skeletal Muscle Atrophy and Modified Arachidonate Metabolism During Hypertrophy

    NASA Technical Reports Server (NTRS)

    Templeton, G.

    1985-01-01

    A previously documented shift from Type I to IIA predominance of the soleus muscle during rat suspension was further investigated to determine if this shift was by selective reduction of a single fiber type, simultaneous reduction and formation of fibers with different fiber types, or a transformation of fiber type by individual fibers. By partial acid digestion and dissection, average total soleus fiber number was found to be 3022 + or - 80 (SE) and 3008 + or - 64 before and after four-week suspension (n=12). Another area of current research was based on previous studies which indicate that prostaglandins are biosynthesized by skeletal muscle and evoke protein synthesis and degradation.

  5. Muscle contraction is required to maintain the pool of muscle progenitors via YAP and NOTCH during fetal myogenesis

    PubMed Central

    Esteves de Lima, Joana; Bonnin, Marie-Ange; Birchmeier, Carmen; Duprez, Delphine

    2016-01-01

    The importance of mechanical activity in the regulation of muscle progenitors during chick development has not been investigated. We show that immobilization decreases NOTCH activity and mimics a NOTCH loss-of-function phenotype, a reduction in the number of muscle progenitors and increased differentiation. Ligand-induced NOTCH activation prevents the reduction of muscle progenitors and the increase of differentiation upon immobilization. Inhibition of NOTCH ligand activity in muscle fibers suffices to reduce the progenitor pool. Furthermore, immobilization reduces the activity of the transcriptional co-activator YAP and the expression of the NOTCH ligand JAG2 in muscle fibers. YAP forced-activity in muscle fibers prevents the decrease of JAG2 expression and the number of PAX7+ cells in immobilization conditions. Our results identify a novel mechanism acting downstream of muscle contraction, where YAP activates JAG2 expression in muscle fibers, which in turn regulates the pool of fetal muscle progenitors via NOTCH in a non-cell-autonomous manner. DOI: http://dx.doi.org/10.7554/eLife.15593.001 PMID:27554485

  6. Muscle fibers are injured at the time of acute and chronic rotator cuff repair.

    PubMed

    Davis, Max E; Stafford, Patrick L; Jergenson, Matthew J; Bedi, Asheesh; Mendias, Christopher L

    2015-01-01

    Rotator cuff tears are a common source of shoulder pain and disability. Even after surgical repair, some patients continue to have reduced function and progression of fatty degeneration. Because patients with chronic cuff tears often experience muscle shortening, it is possible that repairing the tendon to its anatomic footprint induces a stretch-induced muscle injury that could contribute to failures of the repair and perhaps ongoing pain. We hypothesized that, compared with acutely torn and repaired muscles, the stretch that is required to repair a chronically torn cuff would result in more muscle fiber damage. Specifically, we asked: (1) Is there muscle fiber damage that occurs from repair of an acutely torn rotator cuff and does it vary by location in the muscle; and (2) is the damage greater in the case of repair of a chronic injury? We used an open surgical approach to create a full-thickness rotator cuff tear in rats, and measured changes in muscle mass, length, and the number of fibers containing the membrane impermeable Evans Blue Dye after acute (1 day) or chronic (28 days) cuff tear or repair in rats. Differences between groups were tested using a one-way ANOVA followed by Tukey's post hoc sorting. Chronic tears resulted in 24% to 35% decreases in mass and a 20% decrease in length. The repair of acutely and chronically torn muscles resulted in damage to 90% of fibers in the distal portion of the muscle. In the proximal portion, no differences between the acutely torn and repaired groups and controls were observed, whereas repairing the chronically torn group resulted in injury to almost 70% of fibers. In a rat model, marked injury to muscle fibers is induced when the tendons of torn rotator cuffs are repaired to their anatomic footprint. In this animal model, we found that repair of chronically torn cuff muscles results in extensive injury throughout the muscle. Based on these findings, we posit that inducing a widespread injury at the time of surgical

  7. BRANCHED FIBERS FROM OLD FAST-TWITCH DYSTROPHIC MUSCLES ARE THE SITES OF TERMINAL DAMAGE IN MUSCULAR DYSTROPHY.

    PubMed

    Kiriaev, Leonit; Kueh, Sindy; Morley, John W; North, Kathryn N; Houweling, Peter J; Head, Stewart I

    2018-02-07

    A striking pathological feature of dystrophinopathies is the presence of morphologically abnormal branched skeletal muscle fibers. The deterioration of muscle contractile function in Duchenne muscular dystrophy is accompanied by both an increase in number and complexity of these branched fibers. We propose that when number and complexity of branched fibers reaches a critical threshold, "tipping point" the branches in and of themselves are the site of contraction-induced rupture. In the present study, we use the dystrophic mdx mouse and littermate controls to study the pre-diseased dystrophic fast-twitch EDL muscle at 2-3-weeks, the peak myonecrotic phase at 6-9 weeks and finally "old" at 58-112 weeks. Using a combination of isolated muscle function contractile measurements coupled with single fiber imaging and confocal microscope imaging of cleared whole muscles we identified a distinct pathophysiology; acute fiber rupture at branch nodes, which occurs in "old" fast-twitch EDL muscle approaching the end stage of the dystrophinopathy muscle disease, where the EDL muscles are entirely composed of complexed branched fibers. This evidence supports our concept of "tipping point" where the number and extent of fiber branching reaches a level where the branching itself terminally compromises muscle function, irrespective of the absence of dystrophin.

  8. Using laser capture microdissection to study fiber specific signaling in locomotor muscle in COPD: A pilot study.

    PubMed

    Mohan, Divya; Lewis, Amy; Patel, Mehul S; Curtis, Katrina J; Lee, Jen Y; Hopkinson, Nicholas S; Wilkinson, Ian B; Kemp, Paul R; Polkey, Michael I

    2017-06-01

    Quadriceps dysfunction is important in chronic obstructive pulmonary disease (COPD), with an associated increased proportion of type II fibers. Investigation of protein synthesis and degradation has yielded conflicting results, possibly due to study of whole biopsy samples, whereas signaling may be fiber-specific. Our objective was to develop a method for fiber-specific gene expression analysis. 12 COPD and 6 healthy subjects underwent quadriceps biopsy. Cryosections were immunostained for type II fibers, which were separated using laser capture microdissection (LCM). Whole muscle and different fiber populations were subject to quantitative polymerase chain reaction. Levels of muscle-RING-finger-protein-1 and Atrogin-1 were lower in type II fibers of COPD versus healthy subjects (P = 0.02 and P = 0.03, respectively), but differences were not apparent in whole muscle or type I fibers. We describe a novel method for studying fiber-specific gene expression in optimum cutting temperature compound-embedded muscle specimens. LCM offers a more sensitive way to identify molecular changes in COPD muscle. Muscle Nerve 55: 902-912, 2017. © 2016 Wiley Periodicals, Inc.

  9. Experiment K-6-21. Effect of microgravity on 1) metabolic enzymes of type 1 and type 2 muscle fibers and on 2) metabolic enzymes, neutransmitter amino acids, and neurotransmitter associated enzymes in motor and somatosensory cerebral cortex. Part 1: Metabolic enzymes of individual muscle fibers; part 2: metabolic enzymes of hippocampus and spinal cord

    NASA Technical Reports Server (NTRS)

    Lowry, O.; Mcdougal, D., Jr.; Nemeth, Patti M.; Maggie, M.-Y. Chi; Pusateri, M.; Carter, J.; Manchester, J.; Norris, Beverly; Krasnov, I.

    1990-01-01

    The individual fibers of any individual muscle vary greatly in enzyme composition, a fact which is obscured when enzyme levels of a whole muscle are measured. The purpose of this study was therefore to assess the changes due to weightless on the enzyme patterns composed by the individual fibers within the flight muscles. In spite of the limitation in numbers of muscles examined, it is apparent that: (1) that the size of individual fibers (i.e., their dry weight) was reduced about a third, (2) that this loss in dry mass was accompanied by changes in the eight enzymes studied, and (3) that these changes were different for the two muscles, and different for the two enzyme groups. In the soleus muscle the absolute amounts of the three enzymes of oxidative metabolism decreased about in proportion to the dry weight loss, so that their concentration in the atrophic fibers was almost unchanged. In contrast, there was little loss among the four enzymes of glycogenolysis - glycolysis so that their concentrations were substantially increased in the atrophic fibers. In the TA muscle, these seven enzymes were affected in just the opposite direction. There appeared to be no absolute loss among the oxidative enzymes, whereas the glycogenolytic enzymes were reduced by nearly half, so that the concentrations of the first metabolic group were increased within the atrophic fibers and the concentrations of the second group were only marginally decreased. The behavior of hexokinase was exceptional in that it did not decrease in absolute terms in either type of muscle and probably increased as much as 50 percent in soleus. Thus, their was a large increase in concentration of this enzyme in the atrophied fibers of both muscles. Another clear-cut finding was the large increase in the range of activities of the glycolytic enzymes among individual fibers of TA muscles. This was due to the emergence of TA fibers with activities for enzymes of this group extending down to levels as low as

  10. Nandrolone Normalizes Determinants of Muscle Mass and Fiber Type after Spinal Cord Injury

    PubMed Central

    Wu, Yong; Zhao, Jingbo; Zhao, Weidong; Pan, Jiangping; Bauman, William A.

    2012-01-01

    Abstract Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1α protein and PGC-1α mRNA levels. For PGC-1α target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1α in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1α target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation. PMID:22208735

  11. Skeletal muscle fiber type conversion during the repair of mouse soleus: potential implications for muscle healing after injury.

    PubMed

    Matsuura, Tetsuya; Li, Yong; Giacobino, Jean-Paul; Fu, Freddie H; Huard, Johnny

    2007-11-01

    We used a mouse model of cardiotoxin injury to examine fiber type conversion during muscle repair. We evaluated the soleus muscles of 37 wild-type mice at 2, 4, 8, and 12 weeks after injury. We also used antibodies (fMHC and sMHC) against fast and slow myosin heavy chain to classify the myofibers into three categories: fast-, slow-, and mixed (hybrid)-type myofibers (myofibers expressing both fMHC and sMHC). Our results revealed an increase in the percentage of slow-type myofibers and a decrease in the percentage of fast-type myofibers during the repair process. The percentage of hybrid-type myofibers increased 2 weeks after injury, then gradually decreased over the following 6 weeks. Similarly, our analysis of centronucleated myofibers showed an increase in the percentage of slow-type myofibers and decreases in the percentages of fast- and hybrid-type myofibers. We also investigated the relationship between myofiber type conversion and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha). The expression of both PGC-1alpha protein, which is expressed in both the nucleus and the cytoplasm of regenerating myofibers, and sMHC protein increased with time after cardiotoxin injection, but we observed no significant differential expression of fMHC protein in regenerating muscle fibers during muscle repair. PGC-1alpha-positive myofibers underwent fast to slow myofiber type conversion during the repair process. These results suggest that PGC-1alpha contributes to myofiber type conversion after muscle injury and that this phenomenon could influence the recovery of the injured muscle. (c) 2007 Orthopaedic Research Society.

  12. Diet‐induced obesity alters skeletal muscle fiber types of male but not female mice

    PubMed Central

    DeNies, Maxwell S.; Johnson, Jordan; Maliphol, Amanda B.; Bruno, Michael; Kim, Annabelle; Rizvi, Abbas; Rustici, Kevyn; Medler, Scott

    2014-01-01

    Abstract Skeletal muscles are highly plastic tissues capable dramatic remodeling in response to use, disuse, disease, and other factors. Growing evidence suggests that adipose tissues exert significant effects on the basic fiber‐type composition of skeletal muscles. In the current study, we investigated the long‐term effects of a high‐fat diet and subsequent obesity on the muscle fiber types in C57 BLK/6J mice. Litters of mice were randomly assigned to either a high‐fat diet or a control group at the time of weaning, and were maintained on this diet for approximately 1 year. Single fibers were harvested from the soleus and plantaris muscles, and fiber types were determined using SDS‐PAGE. The high‐fat diet mice were significantly heavier than the control mice (39.17 ± 2.7 g vs. 56.87 ± 3.4 g; P < 0.0003), but muscle masses were not different. In male mice, the high‐fat diet was associated with a significantly lower proportion of slow, type I fibers in the soleus muscle (40.4 ± 3.5% vs. 29.33 ± 2.6%; P < 0.0165). Moreover, the proportion of type I fibers in the soleus of male mice was inversely proportional to the relative fatness of the male mice (P < 0.003; r2 = 0.65), but no association was observed in female mice. In male mice, the decline in type I fibers was correlated with an increase in type I/IIA hybrid fibers, suggesting that the type I fibers were transformed primarily into these hybrids. The reported trends indicate that type I fibers are most susceptible to the effects of obesity, and that these fiber‐type changes can be sex specific. PMID:24744883

  13. Effects of Fiber Type and Size on the Heterogeneity of Oxygen Distribution in Exercising Skeletal Muscle

    PubMed Central

    Liu, Gang; Mac Gabhann, Feilim; Popel, Aleksander S.

    2012-01-01

    The process of oxygen delivery from capillary to muscle fiber is essential for a tissue with variable oxygen demand, such as skeletal muscle. Oxygen distribution in exercising skeletal muscle is regulated by convective oxygen transport in the blood vessels, oxygen diffusion and consumption in the tissue. Spatial heterogeneities in oxygen supply, such as microvascular architecture and hemodynamic variables, had been observed experimentally and their marked effects on oxygen exchange had been confirmed using mathematical models. In this study, we investigate the effects of heterogeneities in oxygen demand on tissue oxygenation distribution using a multiscale oxygen transport model. Muscles are composed of different ratios of the various fiber types. Each fiber type has characteristic values of several parameters, including fiber size, oxygen consumption, myoglobin concentration, and oxygen diffusivity. Using experimentally measured parameters for different fiber types and applying them to the rat extensor digitorum longus muscle, we evaluated the effects of heterogeneous fiber size and fiber type properties on the oxygen distribution profile. Our simulation results suggest a marked increase in spatial heterogeneity of oxygen due to fiber size distribution in a mixed muscle. Our simulations also suggest that the combined effects of fiber type properties, except size, do not contribute significantly to the tissue oxygen spatial heterogeneity. However, the incorporation of the difference in oxygen consumption rates of different fiber types alone causes higher oxygen heterogeneity compared to control cases with uniform fiber properties. In contrast, incorporating variation in other fiber type-specific properties, such as myoglobin concentration, causes little change in spatial tissue oxygenation profiles. PMID:23028531

  14. Different responses in soleus muscle fibers of Wistar and Wistar Hannover rats to hindlimb unloading

    NASA Astrophysics Data System (ADS)

    Wang, Xiaodong; Kawano, Fuminori; Terada, Masahiro; Matsuoka, Yoshikazu; Shinoda, Yo; Ishihara, Akihiko; Ohira, Yoshinobu

    2005-08-01

    Effects of 16 days of hindlimb suspension on the characteristics of single soleus muscle fibers were compared between male Wistar and Wistar Hannover rats (5 weeks old). The greater effects of unloading were noted in Wistar Hannover rats. The unloading-related reductions of muscle weight and fiber cross-sectional area vs. the pre-suspension levels were greater than Wistar rats. The percent of fibers expressing pure type I myosin heavy chain (MHC) was decreased and that of type I+II MHC fibers was increased, the magnitudes of these changes were greater than Wistar rats. Total number of myonuclei in control situation was greater in Wistar Hannover rats, but the more numbers of myonuclei were decreased following unloading. Responses of myonuclear domain levels were similar. The numbers of both quiescent and mitotic active satellite cells in control situation were greater in Wistar rats. But the magnitude of the unloading- related decrease was identical for Wistar Hannover and Wistar rats. Although the level of heat shock protein 27 (HSP27) expression in Wistar rats was decreased by unloading, de novo appearance of HSP27 was noted in Wistar Hannover rats. It is suggested that greater responses of soleus muscle fibers of Wistar Hannover than Wistar rats may be related to the different expression of protein, although the precise mechanism is still unclear.

  15. High-fat diet induces skeletal muscle oxidative stress in a fiber type-dependent manner in rats.

    PubMed

    Pinho, Ricardo A; Sepa-Kishi, Diane M; Bikopoulos, George; Wu, Michelle V; Uthayakumar, Abinas; Mohasses, Arta; Hughes, Meghan C; Perry, Christopher G R; Ceddia, Rolando B

    2017-09-01

    This study investigated the effects of high-fat (HF) diet on parameters of oxidative stress among muscles with distinct fiber type composition and oxidative capacities. To accomplish that, male Wistar rats were fed either a low-fat standard chow (SC) or a HF diet for 8 weeks. Soleus, extensor digitorum longus (EDL), and epitrochlearis muscles were collected and mitochondrial H 2 O 2 (mtH 2 O 2 ) emission, palmitate oxidation, and gene expression and antioxidant system were measured. Chronic HF feeding enhanced fat oxidation in oxidative and glycolytic muscles. It also caused a significant reduction in mtH 2 O 2 emission in the EDL muscle, although a tendency towards a reduction was also found in the soleus and epitrochlearis muscles. In the epitrochlearis, HF diet increased mRNA expression of the NADPH oxidase complex; however, this muscle also showed an increase in the expression of antioxidant proteins, suggesting a higher capacity to generate and buffer ROS. The soleus muscle, despite being highly oxidative, elicited H 2 O 2 emission rates equivalent to only 20% and 35% of the values obtained for EDL and epitrochlearis muscles, respectively. Furthermore, the Epi muscle with the lowest oxidative capacity was the second highest in H 2 O 2 emission. In conclusion, it appears that intrinsic differences related to the distribution of type I and type II fibers, rather than oxidative capacity, drove the activity of the anti- and pro-oxidant systems and determine ROS production in different skeletal muscles. This also suggests that the impact of potentially deleterious effects of ROS production on skeletal muscle metabolism/function under lipotoxic conditions is fiber type-specific. Copyright © 2017. Published by Elsevier Inc.

  16. Transversal Stiffness and Young's Modulus of Single Fibers from Rat Soleus Muscle Probed by Atomic Force Microscopy

    PubMed Central

    Ogneva, Irina V.; Lebedev, Dmitry V.; Shenkman, Boris S.

    2010-01-01

    Abstract The structural integrity of striated muscle is determined by extra-sarcomere cytoskeleton that includes structures that connect the Z-disks and M-bands of a sarcomere to sarcomeres of neighbor myofibrils or to sarcolemma. Mechanical properties of these structures are not well characterized. The surface structure and transversal stiffness of single fibers from soleus muscle of the rat were studied with atomic force microscopy in liquid. We identified surface regions that correspond to projections of the Z-disks, M-bands, and structures between them. Transversal stiffness of the fibers was measured in each of these three regions. The stiffness was higher in the Z-disk regions, minimal between the Z-disks and the M-bands, and intermediate in the M-band regions. The stiffness increased twofold when relaxed fibers were maximally activated with calcium and threefold when they were transferred to rigor (ATP-free) solution. Transversal stiffness of fibers heavily treated with Triton X-100 was about twice higher than that of the permeabilized ones, however, its regional difference and the dependence on physiological state of the fiber remained the same. The data may be useful for understanding mechanics of muscle fibers when it is subjected to both axial and transversal strain and stress. PMID:20141755

  17. Developing Laryngeal Muscle of Xenopus laevis as a Model System: Androgen-Driven Myogenesis Controls Fiber Type Transformation

    PubMed Central

    Nasipak, Brian; Kelley, Darcy B.

    2014-01-01

    The developmental programs that contribute to myogenic stem cell proliferation and muscle fiber differentiation control fiber numbers and twitch type. In this study, we describe the use of an experimental model system—androgen-regulated laryngeal muscle of juvenile clawed frogs, Xenopus laevis—to examine the contribution of proliferation by specific populations of myogenic stem cells to expression of the larynx-specific myosin heavy chain isoform, LM. Androgen treatment of juveniles (Stage PM0) resulted in up-regulation of an early (Myf-5) and a late (myogenin) myogenic regulatory factor; the time course of LM up-regulation tracked that of myogenin. Myogenic stem cells stimulated to proliferate by androgen include a population that expresses Pax-7, a marker for the satellite cell myogenic stem cell population. Since androgen can switch muscle fiber types from fast to slow even in denervated larynges, we developed an ex vivo culture system to explore the relation between proliferation and LM expression. Cultured whole larynges maintain sensitivity to androgen, increasing in size and LM expression. Blockade of cell proliferation with cis-platin prevents the switch from slow to fast twitch muscle fibers as assayed by ATPase activity. Blockade of cell proliferation in vivo also resulted in inhibition of LM expression. Thus, both in vivo and ex vivo, inhibition of myogenic stem cell proliferation blocks androgen-induced LM expression and fiber type switching in juveniles. PMID:21954146

  18. Hibernating squirrel muscle activates the endurance exercise pathway despite prolonged immobilization

    PubMed Central

    Xu, Ran; Andres-Mateos, Eva; Mejias, Rebeca; MacDonald, Elizabeth M.; Leinwand, Leslie A.; Merriman, Dana K.; Fink, Rainer H. A.; Cohn, Ronald D.

    2013-01-01

    Skeletal muscle atrophy is a very common clinical challenge in many disuse conditions. Maintenance of muscle mass is crucial to combat debilitating functional consequences evoked from these clinical conditions. In contrast, hibernation represents a physiological state in which there is natural protection against disuse atrophy despite prolonged periods of immobilization and lack of nutrient intake. Even though peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1-α (PGC-1α) is a central mediator in muscle remodeling pathways, its role in the preservation of skeletal muscle mass during hibernation remains unclear. Since PGC-1α regulates muscle fiber type formation and mitochondrial biogenesis, we analyzed muscles of 13-lined ground squirrels. We find that animals in torpor exhibit a shift to slow-twitch Type I muscle fibers. This switch is accompanied by activation of the PGC-1α-mediated endurance exercise pathway. In addition, we observe increased antioxidant capacity without evidence of oxidative stress, a marked decline in apoptotic susceptibility, and enhanced mitochondrial abundance and metabolism. These results show that activation of the endurance exercise pathway can be achieved in vivo despite prolonged periods of immobilization, and therefore might be an important mechanism for skeletal muscle preservation during hibernation. This PGC-1α regulated pathway may be a potential therapeutic target promoting skeletal muscle homeostasis and oxidative balance to prevent muscle loss in a variety of inherited and acquired neuromuscular disease conditions. PMID:23333568

  19. Muscle fiber type distribution in climbing Hawaiian gobioid fishes: ontogeny and correlations with locomotor performance.

    PubMed

    Cediel, Roberto A; Blob, Richard W; Schrank, Gordon D; Plourde, Robert C; Schoenfuss, Heiko L

    2008-01-01

    Three species of Hawaiian amphidromous gobioid fishes are remarkable in their ability to climb waterfalls up to several hundred meters tall. Juvenile Lentipes concolor and Awaous guamensis climb using rapid bursts of axial undulation, whereas juvenile Sicyopterus stimpsoni climb using much slower movements, alternately attaching oral and pelvic sucking disks to the substrate during prolonged bouts of several cycles. Based on these differing climbing styles, we hypothesized that propulsive musculature in juvenile L. concolor and A. guamensis would be dominated by white muscle fibers, whereas S. stimpsoni would exhibit a greater proportion of red muscle fibers than other climbing species. We further predicted that, because adults of these species shift from climbing to burst swimming as their main locomotor behavior, muscle from adult fish of all three species would be dominated by white fibers. To test these hypotheses, we used ATPase assays to evaluate muscle fiber type distribution in Hawaiian climbing gobies for three anatomical regions (midbody, anal, and tail). Axial musculature was dominated by white muscle fibers in juveniles of all three species, but juvenile S. stimpsoni had a significantly greater proportion of red fibers than the other two species. Fiber type proportions of adult fishes did not differ significantly from those of juveniles. Thus, muscle fiber type proportions in juveniles appear to help accommodate differences in locomotor demands among these species, indicating that they overcome the common challenge of waterfall climbing through both diverse behaviors and physiological specializations.

  20. A Physiological Neural Controller of a Muscle Fiber Oculomotor Plant in Horizontal Monkey Saccades

    PubMed Central

    Enderle, John D.

    2014-01-01

    A neural network model of biophysical neurons in the midbrain is presented to drive a muscle fiber oculomotor plant during horizontal monkey saccades. Neural circuitry, including omnipause neuron, premotor excitatory and inhibitory burst neurons, long lead burst neuron, tonic neuron, interneuron, abducens nucleus, and oculomotor nucleus, is developed to examine saccade dynamics. The time-optimal control strategy by realization of agonist and antagonist controller models is investigated. In consequence, each agonist muscle fiber is stimulated by an agonist neuron, while an antagonist muscle fiber is unstimulated by a pause and step from the antagonist neuron. It is concluded that the neural network is constrained by a minimum duration of the agonist pulse and that the most dominant factor in determining the saccade magnitude is the number of active neurons for the small saccades. For the large saccades, however, the duration of agonist burst firing significantly affects the control of saccades. The proposed saccadic circuitry establishes a complete model of saccade generation since it not only includes the neural circuits at both the premotor and motor stages of the saccade generator, but also uses a time-optimal controller to yield the desired saccade magnitude. PMID:24944832

  1. Muscle fiber type, Achilles tendon length, potentiation, and running economy.

    PubMed

    Hunter, Gary R; McCarthy, John P; Carter, Stephen J; Bamman, Marcas M; Gaddy, Emily S; Fisher, Gordon; Katsoulis, Kostantina; Plaisance, Eric P; Newcomer, Bradley R

    2015-05-01

    The purpose of this investigation was to develop a potential model for how muscle fiber type, Achilles tendon length, stretch-shortening cycle potentiation (SSCP), and leg strength interact with running economy. Twenty trained male distance runners 24-40 years of age served as subjects. Running economy (net oxygen uptake) was measured while running on a treadmill. Leg press SSCP(force) and SSCP(velocity) were determined by measuring the difference in velocity between a static leg press throw and a countermovement leg press throw. Vertical jump SSCP was determined by measuring the difference in jump height between a static jump and a drop jump from a 20.3-cm bench. Tendon length was measured by magnetic resonance imaging, and muscle fiber type was made from a vastus lateralis muscle biopsy. Type IIx muscle fiber percent (r = 0.70, p < 0.001) and leg strength (r = 0.95, p < 0.001) were positively and independently related to late eccentric force development. Achilles tendon length (r = 0.42, p ≤ 0.05) and late eccentric force during stretch-shortening cycle (r = 0.76, p < 0.001) were independently related to SSCP(force). SSCP(force) was related to SSCP(velocity), which in turn was related to running economy (r = 0.61, p < 0.01). These results suggest that longer Achilles tendon length, type II fiber, and muscular leg strength may enhance the potential for SSCP, running economy, and physiological effort while running.

  2. Rescue of dystrophic skeletal muscle by PGC-1α involves a fast to slow fiber type shift in the mdx mouse.

    PubMed

    Selsby, Joshua T; Morine, Kevin J; Pendrak, Klara; Barton, Elisabeth R; Sweeney, H Lee

    2012-01-01

    Increased utrophin expression is known to reduce pathology in dystrophin-deficient skeletal muscles. Transgenic over-expression of PGC-1α has been shown to increase levels of utrophin mRNA and improve the histology of mdx muscles. Other reports have shown that PGC-1α signaling can lead to increased oxidative capacity and a fast to slow fiber type shift. Given that it has been shown that slow fibers produce and maintain more utrophin than fast skeletal muscle fibers, we hypothesized that over-expression of PGC-1α in post-natal mdx mice would increase utrophin levels via a fiber type shift, resulting in more slow, oxidative fibers that are also more resistant to contraction-induced damage. To test this hypothesis, neonatal mdx mice were injected with recombinant adeno-associated virus (AAV) driving expression of PGC-1α. PGC-1α over-expression resulted in increased utrophin and type I myosin heavy chain expression as well as elevated mitochondrial protein expression. Muscles were shown to be more resistant to contraction-induced damage and more fatigue resistant. Sirt-1 was increased while p38 activation and NRF-1 were reduced in PGC-1α over-expressing muscle when compared to control. We also evaluated if the use a pharmacological PGC-1α pathway activator, resveratrol, could drive the same physiological changes. Resveratrol administration (100 mg/kg/day) resulted in improved fatigue resistance, but did not achieve significant increases in utrophin expression. These data suggest that the PGC-1α pathway is a potential target for therapeutic intervention in dystrophic skeletal muscle.

  3. Load-dependent mechanical efficiency of individual myosin heads in skeletal muscle fibers activated by laser flash photolysis of caged calcium in the presence of a limited amount of ATP.

    PubMed

    Sugi, H; Iwamoto, H; Akimoto, T; Ushitani, H

    1998-01-01

    Although a contracting muscle regulates its energy output depending on the load imposed on it ("Fenn effect"), the mechanism underlying the load-dependent energy output remains obscure. To explore the possibility that the mechanical efficiency, with which chemical energy derived from ATP hydrolysis is converted into mechanical work, of individual myosin heads changes in a load-dependent manner, we examined the auxotonic shortening of glycerinated rabbit psoas muscle fibers, containing ATP molecules almost equal in number to the myosin heads, following laser flash photolysis of caged calcium. Immediately before laser flash activation, almost all of the myosin heads in the fiber are in the state, M.ADP.Pi, and can undergo only one ATP hydrolysis cycle after activation. When the fibers were activated to shorten under various auxotonic loads, the length, force and power output changes were found to be scaled according to the auxotonic load. Both the power and energy outputs were maximal under a moderate auxotonic load. The amount of M.ADP.Pi utilized at a time after activation was estimated from the amount of isometric force developed after interruption of fiber shortening. This amount was minimal in the isometric condition, and increased nearly in proportion to the distance of fiber shortening. These results are taken as evidence that the efficiency of chemo-mechanical energy conversion in individual myosin heads changes in a load-dependent manner.

  4. [Pathophysiology of muscular atrophy due to disuse--with special reference to a single muscle fiber and its ultrastructure].

    PubMed

    Sukegawa, T

    1983-08-01

    Immobilization muscule atrophy was experimentally induced by fixing one ankle joint with a K-wire in an extended position in rats. The animals were sacrificed at designated intervals to obtain the soleus muscle from the fixed (or disused) side and the free side; the muscles were weighed wet, evaluated (musculo) physiologically using a single-skinned muscle fiber method, and further examined histochemically and electron-microscopically. The wet weight of the disused soleus muscle was reduced to 54% of that of the healthy (used) muscle. According to classification by types of muscle fibers stained for ATPase, conversion of muscle fiber type, i.e., conversions of type 1 (red muscle) into type 2 (white muscle) was noted on the disused side, and similar findings were also observed by examination using a single skinned muscle fiber method. The maximal tension developed by the disused single muscle fiber was lower. This may be attributable to structural changes in the myofilament arrangement observed under an electron microscope. No abnormalities were found in calcium ion uptake by the sarcoplasmic reticulum. Under the present experimental conditions, it was clarified that the disuse atrophy of skeletal muscle induces not only reduction of muscle fibers in diameter but also their dedifferentiation and redifferentiation.

  5. Experiment K-6-07. Metabolic and morphologic properties of muscle fibers after spaceflight

    NASA Technical Reports Server (NTRS)

    Edgerton, R.; Miu, B.; Martin, Thomas P.; Roy, R.; Marini, J.; Leger, J. J.; Oganov, V.; Ilyina-Kakueva, E.

    1990-01-01

    The present study demonstrates that the general capability of skeletal muscle to maintain its proteins decreases rapidly in response to space flight. The present findings suggest further that the magnitude of enzymatic and cell volumes changes in response to space flight depend on several factors including the muscle and its fiber type composition. It appears that in order to associate physiological relevance to the observed enzymatic changes, cell volume should be considered also. Although it remains unclear as to the stimulus, or lack of stimulus, that triggers the rapid changes in muscle proteins in response to space flight, ground-based models of muscle atrophy suggest that the reduction in mechanical loading of muscle may be more important than the total amount of activation over a 24-hr period.

  6. Functional properties of slow and fast gastrocnemius muscle fibers after a 17-day spaceflight

    NASA Technical Reports Server (NTRS)

    Widrick, J. J.; Romatowski, J. G.; Norenberg, K. M.; Knuth, S. T.; Bain, J. L.; Riley, D. A.; Trappe, S. W.; Trappe, T. A.; Costill, D. L.; Fitts, R. H.

    2001-01-01

    The purpose of this investigation was to study the effects of a 17-day spaceflight on the contractile properties of individual fast- and slow-twitch fibers isolated from biopsies of the fast-twitch gastrocnemius muscle of four male astronauts. Single chemically skinned fibers were studied during maximal Ca2+-activated contractions with fiber myosin heavy chain (MHC) isoform expression subsequently determined by SDS gel electrophoresis. Spaceflight had no significant effect on the mean diameter or specific force of single fibers expressing type I, IIa, or IIa/IIx MHC, although a small reduction in average absolute force (P(o)) was observed for the type I fibers (0.68 +/- 0.02 vs. 0.64 +/- 0.02 mN, P < 0.05). Subject-by-flight interactions indicated significant intersubject variation in response to the flight, as postflight fiber diameter and P(o) where significantly reduced for the type I and IIa fibers obtained from one astronaut and for the type IIa fibers from another astronaut. Average unloaded shortening velocity [V(o), in fiber lengths (FL)/s] was greater after the flight for both type I (0.60 +/- 0.03 vs. 0.76 +/- 0.02 FL/s) and IIa fibers (2.33 +/- 0.25 vs. 3.10 +/- 0.16 FL/s). Postflight peak power of the type I and IIa fibers was significantly reduced only for the astronaut experiencing the greatest fiber atrophy and loss of P(o). These results demonstrate that 1) slow and fast gastrocnemius fibers show little atrophy and loss of P(o) but increased V(o) after a typical 17-day spaceflight, 2) there is, however, considerable intersubject variation in these responses, possibly due to intersubject differences in in-flight physical activity, and 3) in these four astronauts, fiber atrophy and reductions in P(o) were less for slow and fast fibers obtained from the phasic fast-twitch gastrocnemius muscle compared with slow and fast fibers obtained from the slow antigravity soleus [J. J. Widrick, S. K. Knuth, K. M. Norenberg, J. G. Romatowski, J. L. W. Bain, D. A

  7. A Contractile Network of Interstitial Cells of Cajal in the Supratarsal Mueller's Smooth Muscle Fibers With Sparse Sympathetic Innervation

    PubMed Central

    Yuzuriha, Shunsuke; Matsuo, Kiyoshi; Ban, Ryokuya; Yano, Shiharu; Moriizumi, Tetsuji

    2012-01-01

    Background: We previously reported that the supratarsal Mueller's muscle is innervated by both sympathetic efferent fibers and trigeminal proprioceptive afferent fibers, which function as mechanoreceptors-inducing reflexive contractions of both the levator and frontalis muscles. Controversy still persists regarding the role of the mechanoreceptors in Mueller's muscle; therefore, we clinically and histologically investigated Mueller's muscle. Methods: We evaluated the role of phenylephrine administration into the upper fornix in contraction of Mueller's smooth muscle fibers and how intraoperative stretching of Mueller's muscle alters the degree of eyelid retraction in 20 patients with aponeurotic blepharoptosis. In addition, we stained Mueller's muscle in 7 cadavers with antibodies against α-smooth muscle actin, S100, tyrosine hydroxylase, c-kit, and connexin 43. Results: Maximal eyelid retraction occurred approximately 3.8 minutes after administration of phenylephrine and prolonged eyelid retraction for at least 20 minutes after administration. Intraoperative stretching of Mueller's muscle increased eyelid retraction due to its reflexive contraction. The tyrosine hydroxylase antibody sparsely stained postganglionic sympathetic nerve fibers, whereas the S100 and c-kit antibodies densely stained the interstitial cells of Cajal (ICCs) among Mueller's smooth muscle fibers. A connexin 43 antibody failed to stain Mueller's muscle. Conclusions: A contractile network of ICCs may mediate neurotransmission within Mueller's multiunit smooth muscle fibers that are sparsely innervated by postganglionic sympathetic fibers. Interstitial cells of Cajal may also serve as mechanoreceptors that reflexively contract Mueller's smooth muscle fibers, forming intimate associations with intramuscular trigeminal proprioceptive fibers to induce reflexive contraction of the levator and frontalis muscles. PMID:22359687

  8. Early effects of carbachol on the morphology of motor endplates of mammalian skeletal muscle fibers.

    PubMed

    Voigt, Tilman

    2010-03-01

    Long-term disturbance of the calcium homeostasis of motor endplates (MEPs) causes necrosis of muscle fibers. The onset of morphological changes in response to this disturbance, particularly in relation to the fiber type, is presently unknown. Omohyoid muscles of mice were incubated for 1-30 minutes in 0.1 mM carbachol, an acetylcholine agonist that causes an inward calcium current. In these muscles, the structural changes of the sarcomeres and the MEP sarcoplasm were evaluated at the light- and electron-microscopic level. Predominantly in type I fibers, carbachol incubation resulted in strong contractures of the sarcomeres underlying the MEPs. Owing to these contractures, the usual beret-like form of the MEP-associated sarcoplasm was deformed into a mushroom-like body. Consequently, the squeezed MEPs partially overlapped the adjacent muscle fiber segments. There are no signs of contractures below the MEPs if muscles were incubated in carbachol in calcium-free Tyrode's solution. Carbachol induced inward calcium current and produced fiber-type-specific contractures. This finding points to differences in the handling of calcium in MEPs. Possible mechanisms for these fiber-type-specific differences caused by carbachol-induced calcium entry are assessed.

  9. Role of ATF4 in skeletal muscle atrophy.

    PubMed

    Adams, Christopher M; Ebert, Scott M; Dyle, Michael C

    2017-05-01

    Here, we discuss recent work focused on the role of activating transcription factor 4 (ATF4) in skeletal muscle atrophy. Muscle atrophy involves and requires widespread changes in skeletal muscle gene expression; however, the transcriptional regulatory proteins responsible for those changes are not yet well defined. Recent work indicates that some forms of muscle atrophy require ATF4, a stress-inducible bZIP transcription factor subunit that helps to mediate a broad range of stress responses in mammalian cells. ATF4 expression in skeletal muscle fibers is sufficient to induce muscle fiber atrophy and required for muscle atrophy during several stress conditions, including aging, fasting, and limb immobilization. By helping to activate specific genes in muscle fibers, ATF4 contributes to the expression of numerous mRNAs, including at least two mRNAs (Gadd45a and p21) that encode mediators of muscle fiber atrophy. Gadd45a promotes muscle fiber atrophy by activating the protein kinase MEKK4. p21 promotes atrophy by reducing expression of spermine oxidase, a metabolic enzyme that helps to maintain muscle fiber size under nonstressed conditions. In skeletal muscle fibers, ATF4 is critical component of a complex and incompletely understood molecular signaling network that causes muscle atrophy during aging, fasting, and immobilization.

  10. Fiber networks amplify active stress

    NASA Astrophysics Data System (ADS)

    Lenz, Martin; Ronceray, Pierre; Broedersz, Chase

    Large-scale force generation is essential for biological functions such as cell motility, embryonic development, and muscle contraction. In these processes, forces generated at the molecular level by motor proteins are transmitted by disordered fiber networks, resulting in large-scale active stresses. While fiber networks are well characterized macroscopically, this stress generation by microscopic active units is not well understood. I will present a comprehensive theoretical study of force transmission in these networks. I will show that the linear, small-force response of the networks is remarkably simple, as the macroscopic active stress depends only on the geometry of the force-exerting unit. In contrast, as non-linear buckling occurs around these units, local active forces are rectified towards isotropic contraction and strongly amplified. This stress amplification is reinforced by the networks' disordered nature, but saturates for high densities of active units. I will show that our predictions are quantitatively consistent with experiments on reconstituted tissues and actomyosin networks, and that they shed light on the role of the network microstructure in shaping active stresses in cells and tissue.

  11. Analysis of fiber type transformation and histology in chronic electrically stimulated canine rectus abdominis muscle island-flap stomal sphincters.

    PubMed

    Majzoub, Ramsey K; Bardoel, Janou W J M; Maldonado, Claudio; Barker, John H; Stadelmann, Wayne K

    2003-01-01

    Dynamic skeletal muscle flaps are designed to perform a specific functional task through contraction and relaxation of their muscle fibers. The most commonly used dynamic skeletal flaps today are for cardiomyoplasty and anal or urinary myoplasty. Low-frequency chronic stimulation of these flaps enables them to use their intrinsic energy stores in a more efficient manner through aerobic metabolic pathways for increased endurance and improved work capacity. The purpose of this study was to (1) determine whether fiber type transformation from fatigue-prone (type II) muscle fibers to fatigue-resistant (type I) muscle fibers could be demonstrated in the authors' chronic canine stomal sphincter model where the rectus abdominis muscle was used to create a functional stomal sphincter, (2) assess whether there is any correlation between the degree of muscle fiber type transformation and the continence times, and (3) examine the long-term effects of the training regimens on the skeletal muscle fibers through histologic and volumetric analysis. Eight dynamic island-flap sphincters were created from a part of the rectus abdominis muscle in mongrel dogs by preserving the deep inferior epigastric vascular pedicle and the most caudal investing intercostal nerve. The muscular sphincters were wrapped around a blind loop of distal ileum and trained with pacing electrodes. Two different training protocols were used. In group A (n = 4), a preexisting anal dynamic graciloplasty training protocol was used. A revised protocol was used in group B (n = 4). Muscle biopsy specimens were obtained before and after training from the rectus abdominis muscle sphincter. Fiber type transformation was assessed using a monoclonal antibody directed against the fatigue-prone type II fibers. Pretraining and posttraining skeletal muscle specimens were examined histologically. A significant fiber type conversion was achieved in both group A and group B animals, with each group achieving greater than 50

  12. Influence of intramuscular fiber orientation on the Achilles tendon curvature using three-dimensional finite element modeling of contracting skeletal muscle.

    PubMed

    Kinugasa, Ryuta; Yamamura, Naoto; Sinha, Shantanu; Takagi, Shu

    2016-10-03

    Tendon curvature plays a key role in mechanical gain (amplifying the joint excursion relative to fiber length change) during joint motion, but the mechanism remains unresolved. A three-dimensional finite element (FE) model was used to investigate the influence of intramuscular fiber orientation upon the curvature pattern of the Achilles tendon during active muscular contraction. Two simulation models, with fiber pennation angles of θ = 25° and 47° were tested for the gastrocnemius and soleus muscles. A smaller pennation angle (25°) of the soleus muscle fibers was accompanied by a large change in curvature whereas a larger pennation angle (47°) of the soleus muscle was accompanied by small effects. These results suggest that the fiber pennation angle determines the curvature of the tendon, and the magnitude of the curvature varies along the length of the aponeurosis. Such FE modeling has the potential of determining changes in force output consequent to changes in intramuscular fiber orientation arising from resistance training or unloading, and provides mechanism for predicting the risk of Achilles tendon ruptures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Function and position determine relative proportions of different fiber types in limb muscles of the lizard Tropidurus psammonastes.

    PubMed

    Pereira, Anieli G; Abdala, Virginia; Kohlsdorf, Tiana

    2015-02-01

    Skeletal muscles can be classified as flexors or extensors according to their function, and as dorsal or ventral according to their position. The latter classification evokes their embryological origin from muscle masses initially divided during limb development, and muscles sharing a given position do not necessarily perform the same function. Here, we compare the relative proportions of different fiber types among six limb muscles in the lizard Tropidurus psammonastes. Individual fibers were classified as slow oxidative (SO), fast glycolytic (FG) or fast oxidative-glycolytic (FOG) based on mitochondrial content; muscles were classified according to position and function. Mixed linear models considering one or both effects were compared using likelihood ratio tests. Variation in the proportion of FG and FOG fibers is mainly explained by function (flexor muscles have on average lower proportions of FG and higher proportions of FOG fibers), while variation in SO fibers is better explained by position (they are less abundant in ventral muscles than in those developed from a dorsal muscle mass). Our results clarify the roles of position and function in determining the relative proportions of the various muscle fibers and provide evidence that these factors may differentially affect distinct fiber types. Copyright © 2014. Published by Elsevier GmbH.

  14. Trigeminal Proprioception Evoked by Strong Stretching of the Mechanoreceptors in Müller's Muscle Induces Reflex Contraction of the Orbital Orbicularis Oculi Slow-Twitch Muscle Fibers.

    PubMed

    Matsuo, Kiyoshi; Ban, Ryokuya; Ban, Midori; Yuzuriha, Shunsuke

    2014-01-01

    The mixed orbicularis oculi muscle lacks an intramuscular proprioceptive system such as muscle spindles, to induce reflex contraction of its slow-twitch fibers. We evaluated whether the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction of the slow-twitch fibers of the orbicularis oculi in addition to those of the levator and frontalis muscles. We evaluated in patients with aponeurosis-disinserted blepharoptosis whether strong stretching of the mechanoreceptors in Müller's muscle from upgaze with unilateral lid load induced reflex contraction of the orbicularis oculi slow-twitch fibers and whether anesthesia of Müller's muscle precluded the contraction. We compared the electromyographic responses of the bilateral orbicularis oculi muscles to unilateral intraoperative direct stimulation of the trigeminal proprioceptive nerve with those to unilateral transcutaneous electrical stimulation of the supraorbital nerve. Upgaze with a unilateral 3-g lid load induced reflex contraction of the bilateral orbicularis oculi muscles with ipsilateral dominance. Anesthesia of Müller's muscle precluded the reflex contraction. The orbicularis oculi reflex evoked by stimulation of the trigeminal proprioceptive nerve differed from that by electrical stimulation of the supraorbital nerve in terms of the intensity of current required to induce the reflex, the absence of R1, and duration. The mechanoreceptors in Müller's muscle functions as an extramuscular proprioceptive system to induce reflex contraction of the orbital orbicularis oculi slow-twitch fibers. Whereas reflex contraction of the pretarsal orbicularis fast-twitch fibers functions in spontaneous or reflex blinking, that of the orbital orbicularis oculi slow-twitch fibers may factor in grimacing and blepharospasm.

  15. Prevention of muscle fibers atrophy during gravitational unloading: The effect of L-arginine administration

    NASA Astrophysics Data System (ADS)

    Kartashkina, N.; Lomonosova, Y.; Shevchenko, T. F.; Bugrova, A. E.; Turtikova, O. V.; Kalamkarov, G. R.; Nemirovskaya, T. L.

    2011-05-01

    Gravitational unloading results in pronounced atrophy of m.soleus. Probably, the output of NO is controlled by the muscle activity. We hypothesized that NO may be involved in the protein metabolism and increase of its concentration in muscle can prevent atrophic changes induced by gravitational unloading. In order to test the hypothesis we applied NO donor L-arginine during gravitational unloading. 2.5-month-old male Wistar rats weighing 220-230g were divided into sedentary control group (CTR, n=7), 14-day hindlimb suspension (HS, n=7), 14 days of hindlimb suspension+ L-arginine (HSL, n=7) (with a daily supplementation of 500 mg/kg wt L-arginine) and 14 days of hindlimb suspension+ L-NAME (HSN, n=7) (90 mg/kg wt during 14 days). Cross sectional area (CSA) of slow twitch (ST) and fast twitch (FT) soleus muscle fibers decreased by 45% and 28% in the HS group ( p<0.05) and 40% and 25% in the HSN group, as compared to the CTR group ( p<0.05), respectively. CSA of ST and FT muscle fibers were 25% and 16% larger in the HSL group in comparison with the HS group ( p<0.05), respectively. The atrophy of FT muscle fibers in the HSL group was completely prevented since FT fiber CSA had no significant differences from the CTR group. In HS group, the percentage of fibers revealing either gaps/disruption of the dystrophin layer of the myofiber surface membrane increased by 27% and 17%, respectively, as compared to the controls (CTR group, p<0.05). The destructions in dystrophin layer integrity and reductions of desmin content were significantly prevented in HSL group. NO concentration decreased by 60% in the HS group (as well as HSN group) and at the same time no changes were detectable in the HSL group. This fact indicates the compensation of NO content in the unloaded muscle under L-arginine administration. The levels of atrogin-1 mRNA were considerably altered in suspended animals (HS group: plus 27%, HSL group: minus 13%) as compared to the control level. Conclusion: L

  16. Life-Long Wheel Running Attenuates Age-Related Fiber Loss in the Plantaris Muscle of Mice: a Pilot Study.

    PubMed

    Suwa, M; Ishioka, T; Kato, J; Komaita, J; Imoto, T; Kida, A; Yokochi, T

    2016-06-01

    The purpose of this study was to investigate whether long-term wheel running would attenuate age-related loss of muscle fiber. Male ICR mice were divided into young (Y, n=12, aged 3 months), old-sedentary (OS, n=5, aged 24 months), and old-exercise (OE, n=6, aged 24 months) groups. The OE group started spontaneous wheel running at 3 months and continued until 24 months of age. Soleus and plantaris muscles were fixed in 4% paraformaldehyde buffer. The fixed muscle was digested in a 50% NaOH solution to isolate single fiber and then fiber number was quantified. The masses of the soleus and plantaris muscles were significantly lower at 24 months than at 3 months of age, and this age-related difference was attenuated by wheel running (P<0.05). Soleus muscle fiber number did not differ among the groups. In the plantaris muscle, the fiber number in the OS group (1 288±92 fibers) was significantly lower than in the Y group (1 874±93 fibers), and this decrease was attenuated in the OE group (1 591±80 fibers) (P<0.05). These results suggest that age-related fiber loss occurs only in the fast-twitch fiber-rich muscle of mice, and that life-long wheel running exercise can prevent this fiber loss. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Slow to fast alterations in skeletal muscle fibers caused by clenbuterol, a beta(2)-receptor agonist

    NASA Technical Reports Server (NTRS)

    Zeman, Richard J.; Ludemann, Robert; Easton, Thomas G.; Etlinger, Joseph D.

    1988-01-01

    The effects of a beta(2)-receptor agonist, clenbuterol, and a beta(2) antagonist, butoxamine, on the skeletal muscle fibers of rats were investigated. It was found that chronic treatment of rats with clenbuterol caused hypertrophy of histochemically identified fast-twitch, but not slow-twitch, fibers within the soleus, while in the extensor digitorum longus the mean areas of both fiber types were increased; in both muscles, the ratio of the number of fast-twitch to slow-twitch fibers was increased. In contrast, a treatment with butoxamine caused a reduction of the fast-twitch fiber size in both muscles, and the ratio of the fast-twitch to slow-twitch fibers was decreased.

  18. Sarcomere Length and Tension Changes in Tetanized Frog Muscle Fibers after Quick Stretches and Releases

    NASA Astrophysics Data System (ADS)

    Sugi, Haruo; Kobayashi, Takakazu

    1983-10-01

    The sarcomere length changes in tetanized frog muscle fibers in response to quick fiber length changes were examined along the fiber length with a high-sensitivity laser diffraction technique. The experiments were only performed with muscle fibers in which the uniform orientation and sarcomere length of the component myofibrils were well preserved during a tetanus. When the sarcomere length changes were recorded near the fixed fiber end, the delay of the onset of sarcomere length change in response to the applied fiber length change tended to be longer than that of the onset of tension changes recorded at the fixed fiber end. The magnitude of sarcomere length changes was larger near the moving fiber end than near the fixed fiber end. In the case of quick releases, the resulting sarcomere shortening tended to outlast the fiber shortening, so that the quick tension recovery started during the sarcomere shortening. These results indicate (i) that the tension changes in response to quick fiber length changes may not give direct information about the cross-bridge properties and (ii) that the viscoelastic multisegmental nature of muscle fibers should be taken into consideration in interpreting the tension responses to quick length changes.

  19. Mitochondrial-nuclear crosstalk, haplotype and copy number variation distinct in muscle fiber type, mitochondrial respiratory and metabolic enzyme activities.

    PubMed

    Liu, Xuan; Trakooljul, Nares; Hadlich, Frieder; Murani, Eduard; Wimmers, Klaus; Ponsuksili, Siriluck

    2017-10-25

    Genes expressed in mitochondria work in concert with those expressed in the nucleus to mediate oxidative phosphorylation (OXPHOS), a process that is relevant for muscle metabolism and meat quality. Mitochondrial genome activity can be efficiently studied and compared in Duroc and Pietrain pigs, which harbor different mitochondrial haplotypes and distinct muscle fiber types, mitochondrial respiratory activities, and fat content. Pietrain pigs homozygous-positive for malignant hyperthermia susceptibility (PiPP) carried only haplotype 8 and showed the lowest absolute mtDNA copy number accompanied by a decrease transcript abundance of mitochondrial-encoded subunits ND1, ND6, and ATP6 and nuclear-encoded subunits NDUFA11 and NDUFB8. In contrast, we found that haplotype 4 of Duroc pigs had significantly higher mitochondrial DNA (mtDNA) copy numbers and an increase transcript abundance of mitochondrial-encoded subunits ND1, ND6, and ATP6. These results suggest that the variation in mitochondrial and nuclear genetic background among these animals has an effect on mitochondrial content and OXPHOS system subunit expression. We observed the co-expression pattern of mitochondrial and nuclear encoded OXPHOS subunits suggesting that the mitochondrial-nuclear crosstalk functionally involves in muscle metabolism. The findings provide valuable information for understanding muscle biology processes and energy metabolism, and may direct use for breeding strategies to improve meat quality and animal health.

  20. Muscle Fiber Size and Function in Elderly Humans: A Longitudinal Study

    USDA-ARS?s Scientific Manuscript database

    Cross-sectional studies are likely to underestimate age-related changes in skeletal muscle strength and mass. The purpose of this longitudinal study was to assess whole muscle and single muscle fiber alterations in the same cohort of 12 older (mean age: start of study=71.1+/-5.4 yrs and end of study...

  1. Effect of 23-day muscle disuse on sarcoplasmic reticulum Ca2+ properties and contractility in human type I and type II skeletal muscle fibers.

    PubMed

    Lamboley, C R; Wyckelsma, V L; Perry, B D; McKenna, M J; Lamb, G D

    2016-08-01

    Inactivity negatively impacts on skeletal muscle function mainly through muscle atrophy. However, recent evidence suggests that the quality of individual muscle fibers is also altered. This study examined the effects of 23 days of unilateral lower limb suspension (ULLS) on specific force and sarcoplasmic reticulum (SR) Ca(2+) content in individual skinned muscle fibers. Muscle biopsies of the vastus lateralis were taken from six young healthy adults prior to and following ULLS. After disuse, the endogenous SR Ca(2+) content was ∼8% lower in type I fibers and maximal SR Ca(2+) capacity was lower in both type I and type II fibers (-11 and -5%, respectively). The specific force, measured in single skinned fibers from three subjects, decreased significantly after ULLS in type II fibers (-23%) but not in type I fibers (-9%). Western blot analyses showed no significant change in the amounts of myosin heavy chain (MHC) I and MHC IIa following the disuse, whereas the amounts of sarco(endo)plasmic reticulum Ca(2+)-ATPase 1 (SERCA1) and calsequestrin increased by ∼120 and ∼20%, respectively, and the amount of troponin I decreased by ∼21%. These findings suggest that the decline in force and power occurring with muscle disuse is likely to be exacerbated in part by reductions in maximum specific force in type II fibers, and in the amount of releasable SR Ca(2+) in both fiber types, the latter not being attributable to a reduced calsequestrin level. Furthermore, the ∼3-wk disuse in human elicits change in SR properties, in particular a more than twofold upregulation in SERCA1 density, before any fiber-type shift. Copyright © 2016 the American Physiological Society.

  2. Energetic aspects of skeletal muscle contraction: implications of fiber types.

    PubMed

    Rall, J A

    1985-01-01

    In this chapter fundamental energetic properties of skeletal muscles as elucidated from isolated muscle preparations are described. Implications of these intrinsic properties for the energetic characterization of different fiber types and for the understanding of locomotion have been considered. Emphasis was placed on the myriad of physical and chemical techniques that can be employed to understand muscle energetics and on the interrelationship of results from different techniques. The anaerobic initial processes which liberate energy during contraction and relaxation are discussed in detail. The high-energy phosphate (approximately P) utilized during contraction and relaxation can be distributed between actomyosin ATPase or cross-bridge cycling (70%) and the Ca2+ ATPase of the sacroplasmic reticulum (30%). Muscle shortening increases the rate of approximately P hydrolysis, and stretching a muscle during contraction suppresses the rate of approximately P hydrolysis. The economy of an isometric contraction is defined as the ratio of isometric mechanical response to energetic cost and is shown to be a fundamental intrinsic parameter describing muscle energetics. Economy of contraction varies across the animal kingdom by over three orders of magnitude and is different in different mammalian fiber types. In mammalian skeletal muscles differences in economy of contraction can be attributed mainly to differences in the specific actomyosin and Ca2+ ATPase of muscles. Furthermore, there is an inverse relationship between economy of contraction and maximum velocity of muscle shortening (Vmax) and maximum power output. This is a fundamental relationship. Muscles cannot be economical at developing and maintaining force and also exhibit rapid shortening. Interestingly, there appears to be a subtle system of unknown nature that modulates the Vmax and economy of contraction. Efficiency of a work-producing contraction is defined and contrasted to the economy of contraction

  3. Effects of cannabinoids on caffeine contractures in slow and fast skeletal muscle fibers of the frog.

    PubMed

    Huerta, Miguel; Ortiz-Mesina, Mónica; Trujillo, Xóchitl; Sánchez-Pastor, Enrique; Vásquez, Clemente; Castro, Elena; Velasco, Raymundo; Montoya-Pérez, Rocío; Onetti, Carlos

    2009-05-01

    The effect of cannabinoids on caffeine contractures was investigated in slow and fast skeletal muscle fibers using isometric tension recording. In slow muscle fibers, WIN 55,212-2 (10 and 5 microM) caused a decrease in tension. These doses reduced maximum tension to 67.43 +/- 8.07% (P = 0.02, n = 5) and 79.4 +/- 14.11% (P = 0.007, n = 5) compared to control, respectively. Tension-time integral was reduced to 58.37 +/- 7.17% and 75.10 +/- 3.60% (P = 0.002, n = 5), respectively. Using the CB(1) cannabinoid receptor agonist ACPA (1 microM) reduced the maximum tension of caffeine contractures by 68.70 +/- 11.63% (P = 0.01, n = 5); tension-time integral was reduced by 66.82 +/- 6.89% (P = 0.02, n = 5) compared to controls. When the CB(1) receptor antagonist AM281 was coapplied with ACPA, it reversed the effect of ACPA on caffeine-evoked tension. In slow and fast muscle fibers incubated with the pertussis toxin, ACPA had no effect on tension evoked by caffeine. In fast muscle fibers, ACPA (1 microM) also decreased tension; the maximum tension was reduced by 56.48 +/- 3.4% (P = 0.001, n = 4), and tension-time integral was reduced by 57.81 +/- 2.6% (P = 0.006, n = 4). This ACPA effect was not statistically significant with respect to the reduction in tension in slow muscle fibers. Moreover, we detected the presence of mRNA for the cannabinoid CB(1) receptor on fast and slow skeletal muscle fibers, which was significantly higher in fast compared to slow muscle fiber expression. In conclusion, our results suggest that in the slow and fast muscle fibers of the frog cannabinoids diminish caffeine-evoked tension through a receptor-mediated mechanism.

  4. Comparison of Muscle Fiber and Meat Quality Characteristics in Different Japanese Quail Lines

    PubMed Central

    Choi, Y. M.; Hwang, S.; Lee, K.

    2016-01-01

    The aim of this study was to compare the growth performance, fiber characteristics of the pectoralis major muscle, and meat quality characteristics in the heavy weight (HW) and random bred control (RBC) quail lines and genders. The HW male exhibited more than two times greater body (245.7 vs 96.1 g, p<0.05) and pectoralis major muscle (PMW; 37.1 vs 11.1 g, p<0.05) weights compared to the RBC female. This growth performance in the HW line was associated with a greater muscle fiber area (1,502 vs 663.0 μm2, p<0.001) compared to the RBC line. Greater muscle mass of the HW male was accompanied by a higher percentage of type IIB fiber compared to the HW female (64.0% vs 51.0%, p<0.05). However, muscle fiber hyperplasia (increase in fiber number) has had a somewhat limited effect on PMW between the two lines. On the other hand, the HW line harboring a higher proportion of type IIB fiber showed rapid pH decline at the early postmortem period (6.23 vs 6.41, p<0.05) and lighter meat surface (53.5 vs 47.3, p<0.05) compared to the RBC line harboring a lower proportion of type IIB fiber. There were no significant differences observed in the measurement of water-holding capacity including drip loss (2.74% vs 3.07%, p>0.05) and cooking loss (21.9% vs 20.4%, p>0.05) between the HW and RBC lines. Therefore, the HW quail line developed by selection from the RBC quail, was slightly different in the meat quality characteristics compared to the RBC line, and a marked difference was found in growth performance between the two quail lines. PMID:27383804

  5. Altered Ca2+ signaling in skeletal muscle fibers of the R6/2 mouse, a model of Huntington’s disease

    PubMed Central

    Braubach, Peter; Orynbayev, Murat; Andronache, Zoita; Hering, Tanja; Landwehrmeyer, Georg Bernhard; Lindenberg, Katrin S.

    2014-01-01

    Huntington’s disease (HD) is caused by an expanded CAG trinucleotide repeat within the gene encoding the protein huntingtin. The resulting elongated glutamine (poly-Q) sequence of mutant huntingtin (mhtt) affects both central neurons and skeletal muscle. Recent reports suggest that ryanodine receptor–based Ca2+ signaling, which is crucial for skeletal muscle excitation–contraction coupling (ECC), is changed by mhtt in HD neurons. Consequently, we searched for alterations of ECC in muscle fibers of the R6/2 mouse, a mouse model of HD. We performed fluorometric recordings of action potentials (APs) and cellular Ca2+ transients on intact isolated toe muscle fibers (musculi interossei), and measured L-type Ca2+ inward currents on internally dialyzed fibers under voltage-clamp conditions. Both APs and AP-triggered Ca2+ transients showed slower kinetics in R6/2 fibers than in fibers from wild-type mice. Ca2+ removal from the myoplasm and Ca2+ release flux from the sarcoplasmic reticulum were characterized using a Ca2+ binding and transport model, which indicated a significant reduction in slow Ca2+ removal activity and Ca2+ release flux both after APs and under voltage-clamp conditions. In addition, the voltage-clamp experiments showed a highly significant decrease in L-type Ca2+ channel conductance. These results indicate profound changes of Ca2+ turnover in skeletal muscle of R6/2 mice and suggest that these changes may be associated with muscle pathology in HD. PMID:25348412

  6. Contractile properties of single permeabilized muscle fibers from congenital cleft palates and normal palates of Spanish goats.

    PubMed

    Hanes, Michael C; Weinzweig, Jeffrey; Kuzon, William M; Panter, Kip E; Buchman, Steven R; Faulkner, John A; Yu, Deborah; Cederna, Paul S; Larkin, Lisa M

    2007-05-01

    Analysis of the composition of muscle fibers constituent to a cleft palate could provide significant insight into the cause of velopharyngeal inadequacy. The authors hypothesized that levator veli palatini muscle dysfunction inherent to cleft palates could affect the timing and outcome of cleft palate repair. Single, permeabilized muscle fibers from levator veli palatini muscles of three normal (n = 19 fibers) and three chemically induced congenital cleft palates (n = 21 fibers) of 14-month-old goats were isolated, and contractile properties were evaluated. The maximum isometric force and rate constants of tension redevelopment (ktr) were measured, and the specific force and normalized power were calculated for each fiber. The ktr measures indicate that cleft fibers are predominantly fast-fatigable; normal fibers are slow fatigue-resistant: after a 10-minute isometric contraction, fibers from cleft palates had a loss of force 16 percent greater than that from normal palates (p = 0.0001). The cross-sectional areas of the fibers from cleft palates (2750 +/- 209 microm2) were greater (p = 0.05) than those from normal palates (2226 +/- 143 microm2). Specific forces did not differ between the two groups. Maximum normalized power of fibers from cleft palates (11.05 +/- 1.82 W/l) was greater (p = 0.0001) than fibers from normal palates (1.60 +/- 0.12 W/l). There are clear physiologic differences in single muscle fibers from cleft palates and normal palates: cleft palate fibers are physiologically fast, have greater fatigability, and have greater power production. Detection of functional and/or fiber type differences in muscles of cleft palates may provide preoperative identification of a patient's susceptibility to velopharyngeal inadequacy and permit early surgical intervention to correct this clinical condition.

  7. Modulation of Muscle Fiber Compositions in Response to Hypoxia via Pyruvate Dehydrogenase Kinase-1

    PubMed Central

    Nguyen, Daniel D.; Kim, Gyuyoup; Pae, Eung-Kwon

    2016-01-01

    Muscle fiber-type changes in hypoxic conditions in accordance with pyruvate dehydrogenase kinase (Pdk)-1 and hypoxia inducible factor (Hif)-1α were investigated in rats. Hif-1α and its down-stream molecule Pdk-1 are well known for readily response to hypoxia. We questioned their roles in relation to changes in myosin heavy chain (MyHC) composition in skeletal muscles. We hypothesize that the level of Pdk-1 with respect to the level of Hif-1α determines MyHC composition of the muscle in rats in hypoxia. Young male rats were housed in a chamber maintained at 11.5% (for sustained hypoxia) or fluctuating between 11.5 and 20.8% (for intermittent hypoxia or IH) oxygen levels. Then, muscle tissues from the geniohyoid (GH), soleus, and anterior tibialis (TA) were obtained at the end of hypoxic conditionings. After both hypoxic conditionings, protein levels of Pdk-1 and Hif-1 increased in GH muscles. GH muscles in acute sustained hypoxia favor an anaerobic glycolytic pathway, resulting in an increase in glycolytic MyHC IIb protein-rich fibers while maintain original fatigue-resistant MyHC IIa protein in the fibers; thus, the numbers of IIa- and IIb MyHC co-expressing fibers increased. Exogenous Pdk-1 over-expression using plasmid vectors elevated not only the glycolytic MyHC IIb, but also IIx as well as IIa expressions in C2C12 myotubes in ambient air significantly. The increase of dual expression of IIa- and IIb MyHC proteins in fibers harvested from the geniohyoid muscle has a potential to improve endurance as shown in our fatigability tests. By increasing the Pdk-1/Hif-1 ratio, a mixed-type muscle could alter endurance within the innate characteristics of the muscle toward more fatigue resistant. We conclude that an increased Pdk-1 level in skeletal muscle helps maintain MyHC compositions to be a fatigue resistant mixed-type muscle. PMID:28018235

  8. A biologically inspired artificial muscle based on fiber-reinforced and electropneumatic dielectric elastomers

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Zhang, Chi; Luo, Meng; Chen, Xi; Li, Dichen; Chen, Hualing

    2017-08-01

    Dielectric elastomers (DEs) have great potential for use as artificial muscles because of the following characteristics: electrical activity, fast and large deformation under stimuli, and softness as natural muscles. Inspired by the traditional McKibben actuators, in this study, we developed a cylindrical soft fiber-reinforced and electropneumatic DE artificial muscle (DEAM) by mimicking the spindle shape of natural muscles. Based on continuum mechanics and variation principle, the inhomogeneous actuation of DEAMs was theoretically modeled and calculated. Prototypes of DEAMs were prepared to validate the design concept and theoretical model. The theoretical predictions are consistent with the experimental results; they successfully predicted the evolutions of the contours of DEAMs with voltage. A pneumatically supported high prestretch in the hoop direction was achieved by our DEAM prototype without buckling the soft fibers sandwiched by the DE films. Besides, a continuously tunable prestretch in the actuation direction was achieved by varying the supporting pressure. Using the theoretical model, the failure modes, maximum actuations, and critical voltages were analyzed; they were highly dependent on the structural parameters, i.e., the cylinder aspect ratio, prestretch level, and supporting pressure. The effects of structural parameters and supporting pressure on the actuation performance were also investigated to optimize the DEAMs.

  9. Modeling the dispersion effects of contractile fibers in smooth muscles

    NASA Astrophysics Data System (ADS)

    Murtada, Sae-Il; Kroon, Martin; Holzapfel, Gerhard A.

    2010-12-01

    Micro-structurally based models for smooth muscle contraction are crucial for a better understanding of pathological conditions such as atherosclerosis, incontinence and asthma. It is meaningful that models consider the underlying mechanical structure and the biochemical activation. Hence, a simple mechanochemical model is proposed that includes the dispersion of the orientation of smooth muscle myofilaments and that is capable to capture available experimental data on smooth muscle contraction. This allows a refined study of the effects of myofilament dispersion on the smooth muscle contraction. A classical biochemical model is used to describe the cross-bridge interactions with the thin filament in smooth muscles in which calcium-dependent myosin phosphorylation is the only regulatory mechanism. A novel mechanical model considers the dispersion of the contractile fiber orientations in smooth muscle cells by means of a strain-energy function in terms of one dispersion parameter. All model parameters have a biophysical meaning and may be estimated through comparisons with experimental data. The contraction of the middle layer of a carotid artery is studied numerically. Using a tube the relationships between the internal pressure and the stretches are investigated as functions of the dispersion parameter, which implies a strong influence of the orientation of smooth muscle myofilaments on the contraction response. It is straightforward to implement this model in a finite element code to better analyze more complex boundary-value problems.

  10. Muscle fiber characteristics and performance correlates of male Olympic-style weightlifters.

    PubMed

    Fry, Andrew C; Schilling, Brian K; Staron, Robert S; Hagerman, Fredrick C; Hikida, Robert S; Thrush, John T

    2003-11-01

    Biopsies fro the vastus lateralis muscle of male weightlifters (WL; n=6; X +/- SE, age=27.0 +/- 2.1 years), and non-weight-trained men (CON; n=7; age=27.0 +/- 2.0 years) were compared for fiber types, myosin heavy chain (MHC) and titin content, and fiber type-specific capillary density. Differences (p<0.05) were observed for percent fiber types IIC (WL=0.4 +/- 0.2, CON=2.4 +/- 0.8); IIA (WL=50.5 +/- 3.2, CON=26.9 +/- 3.7); and IIB (WL=1.7 +/- 1.4, CON=21.0 +/- 5.3), as well as percent MHC IIa (WL=65.3 +/- 2.4, CON=52.1 +/- 4.2) and percent MHC IIB (WL=0.9 +/- 0.9; CON=18.2 +/- 6.1). All WL exhibited only the titin-1 isoform. Capillary density (caps.mm(-2)) for all fiber types combined was greater for the CON subjects (WL=192.7 +/- 17.3; CON=262.9 +/- 26.3), due primarily to a greater capillary density in the IIA fibers. Weightlifting performances and vertical jump power were correlated with type II fiber characteristics. These results suggest that successful weightlifting performance is not dependent on IIB fibers, and that weightlifters exhibit large percentages of type IIA muscle fibers and MHC IIa isoform content.

  11. Distinct skeletal muscle fiber characteristics and gene expression in diet-sensitive versus diet-resistant obesity.

    PubMed

    Gerrits, Martin F; Ghosh, Sujoy; Kavaslar, Nihan; Hill, Benjamin; Tour, Anastasia; Seifert, Erin L; Beauchamp, Brittany; Gorman, Shelby; Stuart, Joan; Dent, Robert; McPherson, Ruth; Harper, Mary-Ellen

    2010-08-01

    Inter-individual variability in weight gain and loss under energy surfeit and deficit conditions, respectively, are well recognized but poorly understood phenomena. We documented weight loss variability in an intensively supervised clinical weight loss program and assessed skeletal muscle gene expression and phenotypic characteristics related to variable response to a 900 kcal regimen. Matched pairs of healthy, diet-compliant, obese diet-sensitive (ODS) and diet-resistant (ODR) subjects were defined as those in the highest and lowest quintiles for weight loss rate. Physical activity energy expenditure was minimal and comparable. Following program completion and weight stabilization, skeletal muscle biopsies were obtained. Gene expression analysis of rectus femoris and vastus lateralis indicated upregulation of genes and gene sets involved in oxidative phosphorylation and glucose and fatty acid metabolism in ODS compared with ODR. In vastus lateralis, there was a higher proportion of oxidative (type I) fibers in ODS compared with ODR women and lean controls, fiber hypertrophy in ODS compared with ODR women and lean controls, and lower succinate dehydrogenase in oxidative and oxidative-glycolytic fibers in all obese compared with lean subjects. Intramuscular lipid content was generally higher in obese versus lean, and specifically higher in ODS vs. lean women. Altogether, our findings demonstrate differences in muscle gene expression and fiber composition related to clinical weight loss success.

  12. Distinct skeletal muscle fiber characteristics and gene expression in diet-sensitive versus diet-resistant obesity

    PubMed Central

    Gerrits, Martin F.; Ghosh, Sujoy; Kavaslar, Nihan; Hill, Benjamin; Tour, Anastasia; Seifert, Erin L.; Beauchamp, Brittany; Gorman, Shelby; Stuart, Joan; Dent, Robert; McPherson, Ruth; Harper, Mary-Ellen

    2010-01-01

    Inter-individual variability in weight gain and loss under energy surfeit and deficit conditions, respectively, are well recognized but poorly understood phenomena. We documented weight loss variability in an intensively supervised clinical weight loss program and assessed skeletal muscle gene expression and phenotypic characteristics related to variable response to a 900 kcal regimen. Matched pairs of healthy, diet-compliant, obese diet-sensitive (ODS) and diet-resistant (ODR) subjects were defined as those in the highest and lowest quintiles for weight loss rate. Physical activity energy expenditure was minimal and comparable. Following program completion and weight stabilization, skeletal muscle biopsies were obtained. Gene expression analysis of rectus femoris and vastus lateralis indicated upregulation of genes and gene sets involved in oxidative phosphorylation and glucose and fatty acid metabolism in ODS compared with ODR. In vastus lateralis, there was a higher proportion of oxidative (type I) fibers in ODS compared with ODR women and lean controls, fiber hypertrophy in ODS compared with ODR women and lean controls, and lower succinate dehydrogenase in oxidative and oxidative-glycolytic fibers in all obese compared with lean subjects. Intramuscular lipid content was generally higher in obese versus lean, and specifically higher in ODS vs. lean women. Altogether, our findings demonstrate differences in muscle gene expression and fiber composition related to clinical weight loss success. PMID:20332421

  13. Trigeminal Proprioception Evoked by Strong Stretching of the Mechanoreceptors in Müller's Muscle Induces Reflex Contraction of the Orbital Orbicularis Oculi Slow-Twitch Muscle Fibers

    PubMed Central

    Ban, Ryokuya; Ban, Midori; Yuzuriha, Shunsuke

    2014-01-01

    Objective: The mixed orbicularis oculi muscle lacks an intramuscular proprioceptive system such as muscle spindles, to induce reflex contraction of its slow-twitch fibers. We evaluated whether the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction of the slow-twitch fibers of the orbicularis oculi in addition to those of the levator and frontalis muscles. Methods: We evaluated in patients with aponeurosis-disinserted blepharoptosis whether strong stretching of the mechanoreceptors in Müller's muscle from upgaze with unilateral lid load induced reflex contraction of the orbicularis oculi slow-twitch fibers and whether anesthesia of Müller's muscle precluded the contraction. We compared the electromyographic responses of the bilateral orbicularis oculi muscles to unilateral intraoperative direct stimulation of the trigeminal proprioceptive nerve with those to unilateral transcutaneous electrical stimulation of the supraorbital nerve. Results: Upgaze with a unilateral 3-g lid load induced reflex contraction of the bilateral orbicularis oculi muscles with ipsilateral dominance. Anesthesia of Müller's muscle precluded the reflex contraction. The orbicularis oculi reflex evoked by stimulation of the trigeminal proprioceptive nerve differed from that by electrical stimulation of the supraorbital nerve in terms of the intensity of current required to induce the reflex, the absence of R1, and duration. Conclusions: The mechanoreceptors in Müller's muscle functions as an extramuscular proprioceptive system to induce reflex contraction of the orbital orbicularis oculi slow-twitch fibers. Whereas reflex contraction of the pretarsal orbicularis fast-twitch fibers functions in spontaneous or reflex blinking, that of the orbital orbicularis oculi slow-twitch fibers may factor in grimacing and blepharospasm. PMID:25210572

  14. Muscle fatigue examined at different temperatures in experiments on intact mammalian (rat) muscle fibers.

    PubMed

    Roots, H; Ball, G; Talbot-Ponsonby, J; King, M; McBeath, K; Ranatunga, K W

    2009-02-01

    In experiments on small bundles of intact fibers from a rat fast muscle, in vitro, we examined the decline in force in repeated tetanic contractions; the aim was to characterize the effect of shortening and of temperature on the initial phase of muscle fatigue. Short tetanic contractions were elicited at a control repetition rate of 1/60 s, and fatigue was induced by raising the rate to 1/5 s for 2-3 min, both in isometric mode (no shortening) and in shortening mode, in which each tetanic contraction included a ramp shortening at a standard velocity. In experiments at 20 degrees C (n = 12), the force decline during a fatigue run was 25% in the isometric mode but was significantly higher (35%) in the shortening mode. In experiments at different temperatures (10-30 degrees C, n = 11), the tetanic frequency and duration were adjusted as appropriate, and for shortening mode, the velocity was adjusted for maximum power output. In isometric mode, fatigue of force was significantly less at 30 degrees C ( approximately 20%) than at 10 degrees C ( approximately 30%); the power output (force x velocity) was >10x higher at 30 degrees C than at 10 degrees C, and power decline during a fatigue run was less at 30 degrees C ( approximately 20-30%) than at 10 degrees C ( approximately 50%). The finding that the extent of fatigue is increased with shortening contractions and is lower at higher temperatures is consistent with the view that force depression by inorganic phosphate, which accumulates within fibers during activity, may be a primary cause of initial muscle fatigue.

  15. Arrest is a regulator of fiber-specific alternative splicing in the indirect flight muscles of Drosophila

    PubMed Central

    Oas, Sandy T.

    2014-01-01

    Drosophila melanogaster flight muscles are distinct from other skeletal muscles, such as jump muscles, and express several uniquely spliced muscle-associated transcripts. We sought to identify factors mediating splicing differences between the flight and jump muscle fiber types. We found that the ribonucleic acid–binding protein Arrest (Aret) is expressed in flight muscles: in founder cells, Aret accumulates in a novel intranuclear compartment that we termed the Bruno body, and after the onset of muscle differentiation, Aret disperses in the nucleus. Down-regulation of the aret gene led to ultrastructural changes and functional impairment of flight muscles, and transcripts of structural genes expressed in the flight muscles became spliced in a manner characteristic of jump muscles. Aret also potently promoted flight muscle splicing patterns when ectopically expressed in jump muscles or tissue culture cells. Genetically, aret is located downstream of exd (extradenticle), hth (homothorax), and salm (spalt major), transcription factors that control fiber identity. Our observations provide insight into a transcriptional and splicing regulatory network for muscle fiber specification. PMID:25246617

  16. Effects of dietary protein restriction on muscle fiber characteristics and mTORC1 pathway in the skeletal muscle of growing-finishing pigs.

    PubMed

    Li, Yinghui; Li, Fengna; Wu, Li; Wei, Hongkui; Liu, Yingying; Li, Tiejun; Tan, Bie; Kong, Xiangfeng; Yao, Kang; Chen, Shuai; Wu, Fei; Duan, Yehui; Yin, Yulong

    2016-01-01

    To investigate the effects of dietary crude protein (CP) restriction on muscle fiber characteristics and key regulators related to protein deposition in skeletal muscle, a total of 18 growing-finishing pigs (62.30 ± 0.88 kg) were allotted to 3 groups and fed with the recommended adequate protein (AP, 16 % CP) diet, moderately restricted protein (MP, 13 % CP) diet and low protein (LP, 10 % CP) diet, respectively. The skeletal muscle of different locations in pigs, including longissimus dorsi muscle (LDM), psoas major muscle (PMM) and biceps femoris muscle (BFM) were collected and analyzed. Results showed that growing-finishing pigs fed the MP or AP diet improved (P < 0.01) the average daily gain and feed: gain ratio compared with those fed the LP diet, and the MP diet tended to increase (P = 0.09) the weight of LDM. Moreover, the ATP content and energy charge value were varied among muscle samples from different locations of pigs fed the reduced protein diets. We also observed that pigs fed the MP diet up-regulated (P < 0.05) muscular mRNA expression of all the selected key genes, except that myosin heavy chain (MyHC) IIb, MyHC IIx, while mRNA expression of ubiquitin ligases genes was not affected by dietary CP level. Additionally, the activation of mammalian target of rapamycin complex 1 (mTORC1) pathway was stimulated (P < 0.05) in skeletal muscle of the pigs fed the MP or AP diet compared with those fed the LP diet. The results suggest that the pigs fed the MP diet could catch up to the growth performance and the LDM weight of the pigs fed the AP diet, and the underlying mechanism may be partly due to the alteration in energy status, modulation of muscle fiber characteristics and mTORC1 activation as well as its downstream effectors in skeletal muscle of different locations in growing-finishing pigs.

  17. Cheap Labor: Myosin fiber type expression and enzyme activity in the forelimb musculature of sloths (Pilosa: Xenarthra).

    PubMed

    Spainhower, Kyle B; Cliffe, Rebecca N; Metz, Allan K; Barkett, Ernest M; Kiraly, Paije M; Thomas, Dylan R; Kennedy, Sarah J; Avey-Arroyo, Judy; Butcher, Michael T

    2018-05-03

    Sloths are canopy-dwelling inhabitants of American neotropical rainforests that exhibit suspensory behaviors. These abilities require both strength and muscular endurance to hang for extended periods of time; however, the skeletal muscle mass of sloths is reduced, thus requiring modifications to muscle architecture and leverage for large joint torque. We hypothesize that intrinsic muscle properties also are modified for fatigue resistance and predict a heterogeneous expression of slow/fast myosin heavy chain (MHC) fibers that utilize oxidative metabolic pathways for economic force production. MHC fiber type distribution and energy metabolism in the forelimb muscles of three-toed ( Bradypus variegatus, N=5) and two-toed ( Choloepus hoffmanni, N=4) sloths were evaluated using SDS-PAGE, immunohistochemistry, and enzyme activity assays. The results partially support our hypothesis by a primary expression of the slow MHC-1 isoform as well as moderate expression of fast MHC-2A fibers, while few hybrid MHC-1/2A fibers were found in both species. MHC-1 fibers were larger in cross-sectional area (CSA) than MHC-2A fibers and comprised the greatest %CSA in each muscle sampled. Enzyme assays showed elevated activity for the anaerobic enzymes creatine kinase (CK) and lactate dehydrogenase (LDH) compared to low activity for aerobic markers citrate synthase (CS) and 3- hydroxyacetyl CoA dehydrogenase (3-HAD). These findings suggest that sloth forelimb muscles may rely heavily on rapid ATP resynthesis pathways, and lactate accumulation may be beneficial. The intrinsic properties observed match well with suspensory requirements, and these modifications may have further evolved in unison with low metabolism and slow movement patterns as means to systemically conserve energy.

  18. [Ultrastructure of the blood vessels and muscle fibers in the skeletal muscle of rats flown on the Kosmos-605 and Kosmos-782 biosatellites].

    PubMed

    Savik, Z F; Rokhlenko, K D

    1981-01-01

    Electron microscopy was used to study ultrastructures of the wall of blood vessels and muscle fibers of the red (soleus) and mixed (gastrocnemius) muscles of rats flown on Cosmos-605 for 22.5 days and on Cosmos-782 for 19,5 days and sacrificed 4-6 hours, 48 hours and 25-27 days postflight. It was demonstrated that the orbital flight did not induce significant changes in the ultrastructure of blood vessels of the soleus and gastrocnemius muscles but caused atrophy of muscle fibers and reduction of the number of functioning capillaries. Readaptation of the soleus vascular system to 1 g led to degradation of permeability of capillary and venular walls and development of edema of the perivascular connective tissue. This may be one of the factors responsible for dystrophic changes in muscle fibers.

  19. A mathematical model of force transmission from intrafascicularly terminating muscle fibers.

    PubMed

    Sharafi, Bahar; Blemker, Silvia S

    2011-07-28

    Many long skeletal muscles are comprised of fibers that terminate intrafascicularly. Force from terminating fibers can be transmitted through shear within the endomysium that surrounds fibers or through tension within the endomysium that extends from fibers to the tendon; however, it is unclear which pathway dominates in force transmission from terminating fibers. The purpose of this work was to develop mathematical models to (i) compare the efficacy of lateral (through shear) and longitudinal (through tension) force transmission in intrafascicularly terminating fibers, and (ii) determine how force transmission is affected by variations in the structure and properties of fibers and the endomysium. The models demonstrated that even though the amount of force that can be transmitted from an intrafascicularly terminating fiber is dependent on fiber resting length (the unstretched length at which passive stress is zero), endomysium shear modulus, and fiber volume fraction (the fraction of the muscle cross-sectional area that is occupied by fibers), fibers that have values of resting length, shear modulus, and volume fraction within physiologic ranges can transmit nearly all of their peak isometric force laterally through shearing of the endomysium. By contrast, the models predicted only limited force transmission ability through tension within the endomysium that extends from the fiber to the tendon. Moreover, when fiber volume fraction decreases to unhealthy ranges (less than 50%), the force-transmitting potential of terminating fibers through shearing of the endomysium decreases significantly. The models presented here support the hypothesis that lateral force transmission through shearing of the endomysium is an effective mode of force transmission in terminating fibers. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Influence of partial activation on force-velocity properties of frog skinned muscle fibers in millimolar magnesium ion

    PubMed Central

    1986-01-01

    Segments of briefly glycerinated muscle fibers from Rana pipiens were activated rapidly by a brief exposure to 2.5 mM free calcium followed by a solution containing calcium buffered with EGTA to produce the desired level of force. Steps to isotonic loads were made using a servomotor, usually 3-5 s after the onset of activation. The relative isotonic forces (P/P0) and velocities from contractions obtained under similar circumstances were grouped together and fitted with hyperbolic functions. Under the condition of 6 mM MgCl2 and 5 mM ATP, there was no significant difference in the relative force-velocity relations obtained at full activation compared with those obtained at partial activation when developed force was approximately 40% of its full value. Control experiments showed that a variety of factors did not alter either the relative force-velocity relations or the finding that partial activation did not change these properties. The factors investigated included the decline in force that occurs with each successive contraction of skinned fibers, the segment length (over a range of 1-3 mm), the sarcomere length (over a range of 1.9-2.2 microns), the magnesium ion concentration (26 microM and 1.4 mM were tested), the ATP concentration, the presence of free calcium, and the age of the preparation (up to 30 h). Attempts to repeat earlier experiments by others showing a dependence of shortening velocity on activation were unsuccessful because the low ionic strength used in those experiments caused the fibers to break after a few contractions. The main conclusion, that the shortening velocity is independent of the level of activation, is consistent with the hypothesis that the cross- bridges act independently and that activating calcium acts only as an all-or-none switch for individual cross-bridge attachment sites, and does not otherwise influence the kinetics of cross-bridge movement. PMID:3486252

  1. Superpixel-based segmentation of muscle fibers in multi-channel microscopy.

    PubMed

    Nguyen, Binh P; Heemskerk, Hans; So, Peter T C; Tucker-Kellogg, Lisa

    2016-12-05

    Confetti fluorescence and other multi-color genetic labelling strategies are useful for observing stem cell regeneration and for other problems of cell lineage tracing. One difficulty of such strategies is segmenting the cell boundaries, which is a very different problem from segmenting color images from the real world. This paper addresses the difficulties and presents a superpixel-based framework for segmentation of regenerated muscle fibers in mice. We propose to integrate an edge detector into a superpixel algorithm and customize the method for multi-channel images. The enhanced superpixel method outperforms the original and another advanced superpixel algorithm in terms of both boundary recall and under-segmentation error. Our framework was applied to cross-section and lateral section images of regenerated muscle fibers from confetti-fluorescent mice. Compared with "ground-truth" segmentations, our framework yielded median Dice similarity coefficients of 0.92 and higher. Our segmentation framework is flexible and provides very good segmentations of multi-color muscle fibers. We anticipate our methods will be useful for segmenting a variety of tissues in confetti fluorecent mice and in mice with similar multi-color labels.

  2. [Effect of glutamate on membrane potential and volume of the skeletal muscle fibers in rats following NO-synthase inhibition in vivo].

    PubMed

    Khairova, P A; Malomuzh, A I; Naumenko, N V; Urazaev, A Kh

    2002-11-01

    Cross-sectional area (CSA) of muscle fibers incubated in culture medium 199 for 3 hours dramatically increases, whereas resting membrane potential (RMP) decreases compared to "freshly-isolated" muscles. Both glutamate and sodium nitroprusside prevent these changes. MK-801, a specific inhibitor of NMDA-receptors, eliminates protective effects of glutamate on both CSA and RMP. NO-synthase inhibition in vivo promotes an increase of initial CSA and decrease of mean RMP. Under these conditions, effects of glutamate and sodium nitroprusside on CSA and RMP of denervated muscles are less obvious. It has been concluded that synaptic glutamate is able to participate in regulation of RMP and cell volume in muscle fibers through the activation of postsynaptic NMDA-receptors and muscle NO-synthase.

  3. Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles.

    PubMed

    Dufresne, Sébastien S; Dumont, Nicolas A; Boulanger-Piette, Antoine; Fajardo, Val A; Gamu, Daniel; Kake-Guena, Sandrine-Aurélie; David, Rares Ovidiu; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M; Pape, Paul C; Tupling, A Russell; Frenette, Jérôme

    2016-04-15

    Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca(2+)sensor, and altered activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) modulating Ca(2+)storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca(2+)storage and SERCA activity, ultimately affecting denervated skeletal muscle function. Copyright © 2016 the American Physiological Society.

  4. Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles

    PubMed Central

    Dufresne, Sébastien S.; Dumont, Nicolas A.; Boulanger-Piette, Antoine; Fajardo, Val A.; Gamu, Daniel; Kake-Guena, Sandrine-Aurélie; David, Rares Ovidiu; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M.; Pape, Paul C.; Tupling, A. Russell

    2016-01-01

    Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca2+ sensor, and altered activity of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) modulating Ca2+ storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca2+ storage and SERCA activity, ultimately affecting denervated skeletal muscle function. PMID:26825123

  5. Depolarization of the Internal Membrane System in the Activation of Frog Skeletal Muscle

    PubMed Central

    Costantin, L. L.; Podolsky, R. J.

    1967-01-01

    "Skinned" muscle fibers, single fibers from the frog semitendinosus muscle in which the sarcolemma had been removed, could be reversibly activated by electrical stimulation. Electrical responsiveness was abolished when the skinned fiber was prepared from a muscle exposed to a cardiac glycoside, and the development of responsiveness was delayed when the muscle was bathed in high potassium solution. The findings were taken as evidence that active sodium-potassium exchange across the internal membranes restored electrical excitability, after the sarcolemma had been removed, by establishing a potential gradient across the internal membranes. In general, the contractions were graded with the strength of the applied current. On occasion, however, "all-or-none" type responses were seen, raising the possibility that the internal membranes were capable of an electrically regenerative response. Activation could also be produced by an elevation of the intracellular chloride ion concentration or a decrease in the intracellular potassium, ion concentration, suggesting that depolarization of some element of the internal membrane system, that is, a decrease in the potential of the lumen of the internal membrane system relative to the potential of the myofibrillar space, was responsible for activation in these experiments. The distribution of both the electrically induced contractions and those produced by changes in the intracellular ion concentrations indicated that the responsive element of the internal membrane system was electrically continuous over many sarcomeres. PMID:6033576

  6. Impact of Western and Mediterranean Diets and Vitamin D on Muscle Fibers of Sedentary Rats

    PubMed Central

    Purrello, Francesco

    2018-01-01

    Background: The metabolic syndrome is associated with sarcopenia. Decreased serum levels of Vitamin D (VitD) and insulin-like growth factor (IGF)-1 and their mutual relationship were also reported. We aimed to evaluate whether different dietary profiles, containing or not VitD, may exert different effects on muscle molecular morphology. Methods: Twenty-eight male rats were fed for 10 weeks in order to detect early defects induced by different dietary regimens: regular diet (R); regular diet with vitamin D supplementation (R-DS) and regular diet with vitamin D restriction (R-DR); high-fat butter-based diets (HFB-DS and HFB-DR) with 41% energy from fat; high-fat extra-virgin olive oil-based diets (HFEVO-DS and HFEVO-DR) with 41% energy from fat. IL-1β, insulin-like growth factor (IGF)1, Dickkopf-1 (DKK-1), and VitD-receptor (VDR) expressions were evaluated by immunohistochemistry. Muscle fiber perimeter was measured by histology and morphometric analysis. Results: The muscle fibers of the HEVO-DS rats were hypertrophic, comparable to those of the R-DS rats. An inverse correlation existed between the dietary fat content and the perimeter of the muscle fibers (p < 0.01). In the HFB-DR rats, the muscle fibers appeared hypotrophic with an increase of IL-1β and a dramatic decrease of IGF-1 expression. Conclusions: High-fat western diet could impair muscle metabolism and lay the ground for subsequent muscle damage. VitD associated with a Mediterranean diet showed trophic action on the muscle fibers. PMID:29462978

  7. Chapter 2. Calcineurin signaling and the slow oxidative skeletal muscle fiber type.

    PubMed

    Mallinson, Joanne; Meissner, Joachim; Chang, Kin-Chow

    2009-01-01

    Calcineurin, also known as protein phosphatase 2B (PP2B), is a calcium-calmodulin-dependent phosphatase. It couples intracellular calcium to dephosphorylate selected substrates resulting in diverse biological consequences depending on cell type. In mammals, calcineurin's functions include neuronal growth, development of cardiac valves and hypertrophy, activation of lymphocytes, and the regulation of ion channels and enzymes. This chapter focuses on the key roles of calcineurin in skeletal muscle differentiation, regeneration, and fiber type conversion to an oxidative state, all of which are crucial to muscle development, metabolism, and functional adaptations. It seeks to integrate the current knowledge of calcineurin signaling in skeletal muscle and its interactions with other prominent regulatory pathways and their signaling intermediates to form a molecular overview that could provide directions for possible future exploitations in human metabolic health.

  8. In Vivo Microscopy Reveals Extensive Embedding of Capillaries within the Sarcolemma of Skeletal Muscle Fibers

    PubMed Central

    Glancy, Brian; Hsu, Li-Yueh; Dao, Lam; Bakalar, Matthew; French, Stephanie; Chess, David J.; Taylor, Joni L.; Picard, Martin; Aponte, Angel; Daniels, Mathew P.; Esfahani, Shervin; Cushman, Samuel; Balaban, Robert S.

    2013-01-01

    Objective To provide insight into mitochondrial function in vivo, we evaluated the 3D spatial relationship between capillaries, mitochondria, and muscle fibers in live mice. Methods 3D volumes of in vivo murine Tibialis anterior muscles were imaged by multi-photon microscopy (MPM). Muscle fiber type, mitochondrial distribution, number of capillaries, and capillary-to-fiber contact were assessed. The role of myoglobin-facilitated diffusion was examined in myoglobin knockout mice. Distribution of GLUT4 was also evaluated in the context of the capillary and mitochondrial network. Results MPM revealed that 43.6 ± 3.3% of oxidative fiber capillaries had ≥ 50% of their circumference embedded in a groove in the sarcolemma, in vivo. Embedded capillaries were tightly associated with dense mitochondrial populations lateral to capillary grooves and nearly absent below the groove. Mitochondrial distribution, number of embedded capillaries, and capillary-to-fiber contact were proportional to fiber oxidative capacity and unaffected by myoglobin knockout. GLUT4 did not preferentially localize to embedded capillaries. Conclusions Embedding capillaries in the sarcolemma may provide a regulatory mechanism to optimize delivery of oxygen to heterogeneous groups of muscle fibers. We hypothesize that mitochondria locate to paravascular regions due to myofibril voids created by embedded capillaries, not to enhance the delivery of oxygen to the mitochondria. PMID:25279425

  9. Myomaker: A membrane activator of myoblast fusion and muscle formation

    PubMed Central

    Millay, Douglas P.; O’Rourke, Jason R.; Sutherland, Lillian B.; Bezprozvannaya, Svetlana; Shelton, John M.; Bassel-Duby, Rhonda; Olson, Eric N.

    2013-01-01

    Summary Fusion of myoblasts is essential for the formation of multi-nucleated muscle fibers. However, the identity of myogenic proteins that directly govern this fusion process has remained elusive. Here, we discovered a muscle-specific membrane protein, named Myomaker, that controls myoblast fusion. Myomaker is expressed on the cell surface of myoblasts during fusion and is down-regulated thereafter. Over-expression of Myomaker in myoblasts dramatically enhances fusion and genetic disruption of Myomaker in mice causes perinatal death due to an absence of multi-nucleated muscle fibers. Remarkably, forced expression of Myomaker in fibroblasts promotes fusion with myoblasts, demonstrating the direct participation of this protein in the fusion process. Pharmacologic perturbation of the actin cytoskeleton abolishes the activity of Myomaker, consistent with prior studies implicating actin dynamics in myoblast fusion. These findings reveal a long-sought myogenic fusion protein both necessary and sufficient for mammalian myoblast fusion and provide new insights into the molecular underpinnings of muscle formation. PMID:23868259

  10. Passive stretch reduces calpain activity through nitric oxide pathway in unloaded soleus muscles.

    PubMed

    Xu, Peng-Tao; Li, Quan; Sheng, Juan-Juan; Chang, Hui; Song, Zhen; Yu, Zhi-Bin

    2012-08-01

    Unloading in spaceflight or long-term bed rest induces to pronounced atrophy of anti-gravity skeletal muscles. Passive stretch partially resists unloading-induced atrophy of skeletal muscle, but the mechanism remains elusive. The aims of this study were to investigate the hypotheses that stretch tension might increase protein level of neuronal nitric oxide synthase (nNOS) in unloaded skeletal muscle, and then nNOS-derived NO alleviated atrophy of skeletal muscle by inhibiting calpain activity. The tail-suspended rats were used to unload rat hindlimbs for 2 weeks, at the same time, left soleus muscle was stretched by applying a plaster cast to fix the ankle at 35° dorsiflexion. Stretch partially resisted atrophy and inhibited the decreased protein level and activity of nNOS in unloaded soleus muscles. Unloading increased frequency of calcium sparks and elevated intracellular resting and caffeine-induced Ca(2+) concentration ([Ca(2+)]i) in unloaded soleus muscle fibers. Stretch reduced frequency of calcium sparks and restored intracellular resting and caffeine-induced Ca(2+) concentration to control levels in unloaded soleus muscle fibers. The increased protein level and activity of calpain as well as the higher degradation of desmin induced by unloading were inhibited by stretch in soleus muscles. In conclusion, these results suggest that stretch can preserve the stability of sarcoplasmic reticulum Ca(2+) release channels which prevents the elevated [Ca(2+)]i by means of keeping nNOS activity, and then the enhanced protein level and activity of calpain return to control levels in unloaded soleus muscles. Therefore, stretch can resist in part atrophy of unloaded soleus muscles.

  11. Long-term high-level exercise promotes muscle reinnervation with age.

    PubMed

    Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Fruhmann, Hannah; Vogelauer, Michael; Burggraf, Samantha; Mayr, Winfried; Krenn, Matthias; Paternostro-Sluga, Tatjana; Hamar, Dusan; Cvecka, Jan; Sedliak, Milan; Tirpakova, Veronika; Sarabon, Nejc; Musarò, Antonio; Sandri, Marco; Protasi, Feliciano; Nori, Alessandra; Pond, Amber; Zampieri, Sandra

    2014-04-01

    The histologic features of aging muscle suggest that denervation contributes to atrophy, that immobility accelerates the process, and that routine exercise may protect against loss of motor units and muscle tissue. Here, we compared muscle biopsies from sedentary and physically active seniors and found that seniors with a long history of high-level recreational activity up to the time of muscle biopsy had 1) lower loss of muscle strength versus young men (32% loss in physically active vs 51% loss in sedentary seniors); 2) fewer small angulated (denervated) myofibers; 3) a higher percentage of fiber-type groups (reinnervated muscle fibers) that were almost exclusive of the slow type; and 4) sparse normal-size muscle fibers coexpressing fast and slow myosin heavy chains, which is not compatible with exercise-driven muscle-type transformation. The biopsies from the old physically active seniors varied from sparse fiber-type groupings to almost fully transformed muscle, suggesting that coexpressing fibers appear to fill gaps. Altogether, the data show that long-term physical activity promotes reinnervation of muscle fibers and suggest that decades of high-level exercise allow the body to adapt to age-related denervation by saving otherwise lost muscle fibers through selective recruitment to slow motor units. These effects on size and structure of myofibers may delay functional decline in late aging.

  12. Recovery from muscle weakness by exercise and FES: lessons from Masters, active or sedentary seniors and SCI patients.

    PubMed

    Carraro, Ugo; Kern, Helmut; Gava, Paolo; Hofer, Christian; Loefler, Stefan; Gargiulo, Paolo; Edmunds, Kyle; Árnadóttir, Íris Dröfn; Zampieri, Sandra; Ravara, Barbara; Gava, Francesco; Nori, Alessandra; Gobbo, Valerio; Masiero, Stefano; Marcante, Andrea; Baba, Alfonc; Piccione, Francesco; Schils, Sheila; Pond, Amber; Mosole, Simone

    2017-08-01

    Many factors contribute to the decline of skeletal muscle that occurs as we age. This is a reality that we may combat, but not prevent because it is written into our genome. The series of records from World Master Athletes reveals that skeletal muscle power begins to decline at the age of 30 years and continues, almost linearly, to zero at the age of 110 years. Here we discuss evidence that denervation contributes to the atrophy and slowness of aged muscle. We compared muscle from lifelong active seniors to that of sedentary elderly people and found that the sportsmen have more muscle bulk and slow fiber type groupings, providing evidence that physical activity maintains slow motoneurons which reinnervate muscle fibers. Further, accelerated muscle atrophy/degeneration occurs with irreversible Conus and Cauda Equina syndrome, a spinal cord injury in which the human leg muscles may be permanently disconnected from the nervous system with complete loss of muscle fibers within 5-8 years. We used histological morphometry and Muscle Color Computed Tomography to evaluate muscle from these peculiar persons and reveal that contraction produced by home-based Functional Electrical Stimulation (h-bFES) recovers muscle size and function which is reversed if h-bFES is discontinued. FES also reverses muscle atrophy in sedentary seniors and modulates mitochondria in horse muscles. All together these observations indicate that FES modifies muscle fibers by increasing contractions per day. Thus, FES should be considered in critical care units, rehabilitation centers and nursing facilities when patients are unable or reluctant to exercise.

  13. An Overview of Laryngeal Muscle Single Fiber Electromyography.

    PubMed

    Bertorini, Tulio E; Sharaf, Aboubakar G

    2015-08-01

    Needle electromyography is an important tool in the diagnosis of neuromuscular diseases and has also been applied successfully in the evaluation of the vocal cord paralysis. Laryngeal electromyography, initially described by Weddell, is used to determine the cause of vocal cord paralysis and to differentiate organic from nonorganic causes of speech disorders. This test allows the diagnosis of lower motor neuron and nerve paralysis as well as myopathies. Laryngeal electromyography also helps to determine the prognosis of paralysis caused by traumatic injury of the laryngeal nerves and is used for guidance during botulinum toxin injection in spasmodic dysphonias. Single fiber electromyography is used to diagnose abnormalities of neuromuscular transmission and is applied in the study the architecture of the motor unit in muscles. This article reviews the techniques of laryngeal muscles single fiber electromyography, provides limited informative data, and discusses its potential value in the evaluation of patients with dysphonia.

  14. Memristive Model of the Barnacle Giant Muscle Fibers

    NASA Astrophysics Data System (ADS)

    Sah, Maheshwar Pd.; Kim, Hyongsuk; Eroglu, Abdullah; Chua, Leon

    The generation of action potentials (oscillations) in biological systems is a complex, yet poorly understood nonlinear dynamical phenomenon involving ions. This paper reveals that the time-varying calcium ion and the time-varying potassium ion, which are essential for generating action potentials in Barnacle giant muscle fibers are in fact generic memristors in the perspective of electrical circuit theory. We will show that these two ions exhibit all the fingerprints of memristors from the equations of the Morris-Lecar model of the Barnacle giant muscle fibers. This paper also gives a textbook reference to understand the difference between memristor and nonlinear resistor via analysis of the potassium ion-channel memristor and calcium ion-channel nonlinear resistor. We will also present a comprehensive in-depth analysis of the generation of action potentials (oscillations) in memristive Morris-Lecar model using small-signal circuit model and the Hopf bifurcation theorem.

  15. Creatine Supplementation Induces Alteration in Cross-Sectional Area in Skeletal Muscle Fibers of Wistar Rats Under Swimming Training

    PubMed Central

    Santos, Fernando Farias Dos; Moura, José A. A.; Curi, Rui; Fernandes, Luiz C.

    2002-01-01

    Creatine has been shown to increase the total muscle mass. In this study, we investigated the effect of oral creatine monohydrate supplementation on cross-sectional area of type I, IIA and IIB fibers of gastrocnemius, extensor digitorum longus - EDL and soleus muscles from male Wistar rats subjected to swimming training for 33 days. Four groups were set up: sedentary with no supplementation (CON), sedentary with creatine supplementation (3.3 mg creatine per g chow) (CR), exercised with no supplementation (EX) and exercised with supplementation (CREX). The rats performed in a special swimming pool and swam five times a week for 1 hour each day, with a extra lead weight corresponding to 15% of their body weight. At the end of 33 days, skeletal muscles of the animals were dissected and the samples got immediately frozen using liquid nitrogen. Muscle samples were allocated to slices of 10 μm by a cryostat at -20°C, which was followed by histochemical analysis in order to identify fiber types of the muscles, and morphometrical analysis to calculate the muscle fiber areas. All groups gained body weight at the end of 33 days but there was no statistical difference among them. The EX and CREX rats had a larger food intake than the sedentary groups (CON and CR), and the CREX group had a larger food intake than CR rats. The cross-sectional area of type I and IIA fibers of the soleus muscle, type IIA and IIB fibers of EDL muscle and type IIA and IIB fibers of the white portion of gastrocnemius muscle were greater in the EX and CREX groups in comparison to sedentary rats. In addition, these fibers were greater in the CREX rats than in the EX group. There was no change in the cross sectional area of type I fibers in EDL muscle among all groups studied. Our results suggest that creatine supplementation enhances the exercise related muscle fiber hypertrophy in rodents. PMID:24701129

  16. Bion 11 Spaceflight Project: Effect of Weightlessness on Single Muscle Fiber Function in Rhesus Monkeys

    NASA Technical Reports Server (NTRS)

    Fitts, Robert H.; Romatowski, Janell G.; Widrick, Jeffrey J.; DeLaCruz, Lourdes

    1999-01-01

    Although it is well known that microgravity induces considerable limb muscle atrophy, little is known about how weightlessness alters cell function. In this study, we investigated how weightlessness altered the functional properties of single fast and slow striated muscle fibers. Physiological studies were carried out to test the hypothesis that microgravity causes fiber atrophy, a decreased peak force (Newtons), tension (Newtons/cross-sectional area) and power, an elevated peak rate of tension development (dp/dt), and an increased maximal shortening velocity (V(sub o)) in the slow type I fiber, while changes in the fast-twitch fiber are restricted to atrophy and a reduced peak force. For each fiber, we determined the peak force (P(sub o)), V(sub o), dp/dt, the force-velocity relationship, peak power, the power-force relationship, the force-pCa relationship, and fiber stiffness. Biochemical studies were carried out to assess the effects of weightlessness on the enzyme and substrate profile of the fast- and slow-twitch fibers. We predicted that microgravity would increase resting muscle glycogen and glycolytic metabolism in the slow fiber type, while the fast-twitch fiber enzyme profile would be unaltered. The increased muscle glycogen would in part result from an elevated hexokinase and glycogen synthase. The enzymes selected for study represent markers for mitochondrial function (citrate synthase and 0-hydroxyacyl-CoA dehydrogenase), glycolysis (Phosphofructokinase and lactate dehydrogenase), and fatty acid transport (Carnitine acetyl transferase). The substrates analyzed will include glycogen, lactate, adenosine triphosphate, and phosphocreatine.

  17. Fiber Typing of the Erector Spinae and Multifidus Muscles in Healthy Controls and Back Pain Patients: A Systematic Literature Review.

    PubMed

    Cagnie, Barbara; Dhooge, Famke; Schumacher, Charline; De Meulemeester, Kayleigh; Petrovic, Mirko; van Oosterwijck, Jessica; Danneels, Lieven

    2015-01-01

    Understanding the changes in muscle fiber typing is relevant in the context of muscle disorders because it provides information on the metabolic profile and functional capacity. The aim of this study was to systematically review the literature comparing muscle fiber typing in the back muscles of healthy subjects with low back pain (LBP) patients. Predefined keywords regarding muscle fiber typing and back muscles were combined in PubMed and Web of Science electronic search engines from inception to August 2014. Full-text articles were independently screened by 2 independent, blinded researchers. Full texts fulfilling the predefined inclusion criteria were assessed on risk of bias by 2 independent researchers, and relative data were extracted. Data were not pooled because of heterogeneity in biopsy locations and population. From the 214 articles that were identified, 18 met the inclusion criteria. These articles evaluated the muscle fiber type distribution or proportional fiber type area between muscles, muscle layers, men, and women or healthy subjects and LBP patients. Regarding muscle fiber type distribution, findings in healthy subjects and LBP patients show no or inconclusive evidence for intermuscular and interindividual differentiation. Studies evaluating the proportional fiber type area also suggest little intermuscular differentiation but provide plausible evidence that the proportional area occupied by type I fibers is higher in women compared to men. The evidence for differentiation based on the presence of low back pain is conflicting. This study found that the evidence regarding muscle fiber typing in back muscles is either inconclusive or shows little differences. The most plausible evidence exists for differentiation in proportional fiber type area depending on sex. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  18. Muscle fiber type characteristics in females with chronic obstructive pulmonary disease. A preliminary study.

    PubMed

    Green, Howard J; Burnett, M E; D'Arsigny, C; Iqbal, S; Ouyang, J; Webb, K A; O'Donnell, D E

    2009-02-01

    Chronic obstructive pulmonary disease (COPD) is known to elicit intrinsic abnormalities in male skeletal muscle. However, it is unclear to what extent these changes occur in women and whether they are fiber-type specific. We investigated fiber-type specific differences in selected histochemical properties in muscle obtained from women with moderate to severe COPD compared to healthy control (CON) women. Tissue was obtained from the vastus lateralis in five COPD patients (age 66.9 +/- 2.6 years; FEV1 = 43 +/- 7%) and eight CON (age 68 +/- 4.9 years; FEV1 = 113 +/- 4.2%). Compared to CON, the distribution (30.6 +/- 5.2 vs. 57.9 +/- 4.6%) and cross sectional area of type I (CSA, 5660 +/- 329 vs. 3586 +/- 257 microm2) and type IIA (2770 +/- 302 vs. 2099 +/- 206 microm2) were lower (P < 0.05) and higher (P < 0.05), respectively, in COPD. Disease state did not alter either the distribution or CSA of the IIA, IIAX or type X subtypes. Although differences were found between fiber types in the number of capillary contacts (n) (I > IIAX, IIX; IIA > IIX) and the capillaries per CSA (microm210(-3)) (I < IIA, IIAX, IIX), no differences were found between CON and COPD. Succinic dehydrogenase activity and sarcoplasmic reticulum (SR) Ca2+-ATPase activity, measured photometrically (OD units), were higher (P < 0.05), and lower (P < 0.05), respectively, in type I compared to the type II fiber subtypes. These properties were not altered with COPD. COPD in females is accompanied by a higher percent of type II fibers, a larger CSA of type I and type IIA fibers, both of which occur in the absence of differences in oxidative potential and the potential for SR Ca2+-sequestration.

  19. Could the peristaltic transition zone be caused by non-uniform esophageal muscle fiber architecture? A simulation study.

    PubMed

    Kou, W; Pandolfino, J E; Kahrilas, P J; Patankar, N A

    2017-06-01

    Based on a fully coupled computational model of esophageal transport, we analyzed how varied esophageal muscle fiber architecture and/or dual contraction waves (CWs) affect bolus transport. Specifically, we studied the luminal pressure profile in those cases to better understand possible origins of the peristaltic transition zone. Two groups of studies were conducted using a computational model. The first studied esophageal transport with circumferential-longitudinal fiber architecture, helical fiber architecture and various combinations of the two. In the second group, cases with dual CWs and varied muscle fiber architecture were simulated. Overall transport characteristics were examined and the space-time profiles of luminal pressure were plotted and compared. Helical muscle fiber architecture featured reduced circumferential wall stress, greater esophageal distensibility, and greater axial shortening. Non-uniform fiber architecture featured a peristaltic pressure trough between two high-pressure segments. The distal pressure segment showed greater amplitude than the proximal segment, consistent with experimental data. Dual CWs also featured a pressure trough between two high-pressure segments. However, the minimum pressure in the region of overlap was much lower, and the amplitudes of the two high-pressure segments were similar. The efficacy of esophageal transport is greatly affected by muscle fiber architecture. The peristaltic transition zone may be attributable to non-uniform architecture of muscle fibers along the length of the esophagus and/or dual CWs. The difference in amplitude between the proximal and distal pressure segments may be attributable to non-uniform muscle fiber architecture. © 2017 John Wiley & Sons Ltd.

  20. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

    PubMed

    Mijwel, Sara; Cardinale, Daniele A; Norrbom, Jessica; Chapman, Mark; Ivarsson, Niklas; Wengström, Yvonne; Sundberg, Carl Johan; Rundqvist, Helene

    2018-05-11

    Exercise has been suggested to ameliorate the detrimental effects of chemotherapy on skeletal muscle. The aim of this study was to compare the effects of different exercise regimens with usual care on skeletal muscle morphology and mitochondrial markers in patients being treated with chemotherapy for breast cancer. Specifically, we compared moderate-intensity aerobic training combined with high-intensity interval training (AT-HIIT) and resistance training combined with high-intensity interval training (RT-HIIT) with usual care (UC). Resting skeletal muscle biopsies were obtained pre- and postintervention from 23 randomly selected women from the OptiTrain breast cancer trial who underwent RT-HIIT, AT-HIIT, or UC for 16 wk. Over the intervention, citrate synthase activity, muscle fiber cross-sectional area, capillaries per fiber, and myosin heavy chain isoform type I were reduced in UC, whereas RT-HIIT and AT-HIIT were able to counteract these declines. AT-HIIT promoted up-regulation of the electron transport chain protein levels vs. UC. RT-HIIT favored satellite cell count vs. UC and AT-HIIT. There was a significant association between change in citrate synthase activity and self-reported fatigue. AT-HIIT and RT-HIIT maintained or improved markers of skeletal muscle function compared with the declines found in the UC group, indicating a sustained trainability in addition to the preservation of skeletal muscle structural and metabolic characteristics during chemotherapy. These findings highlight the importance of supervised exercise programs for patients with breast cancer during chemotherapy.-Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengström, Y., Sundberg, C. J., Rundqvist, H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

  1. Alpine Skiing With total knee ArthroPlasty (ASWAP): metabolism, inflammation, and skeletal muscle fiber characteristics.

    PubMed

    Kristensen, M; Pötzelsberger, B; Scheiber, P; Bergdahl, A; Hansen, C N; Andersen, J L; Narici, M; Salvioli, S; Conte, M; Müller, E; Dela, F

    2015-08-01

    We investigated the effect of alpine skiing for 12 weeks on skeletal muscle characteristics and biomarkers of glucose homeostasis and cardiovascular risk factors. Twenty-three patients with a total knee arthroplasty (TKA) were studied 2.9 ± 0.9 years (mean ± SD) after the operation. Fourteen patients participated in the intervention group (IG) and nine in the control group (CG). Blood samples and muscle biopsies were obtained before (PRE) and 7.3 ± 0.8 days after (POST) the intervention, and blood samples again after a retention (RET) phase of 8 weeks. With skiing, glucose homeostasis improved in IG (decrease in fasting insulin, increase in muscle glycogen) but not in CG. Fiber type distribution and size, as well as capillary density and number of capillaries around the fibers (CAF), were not different between the operated and the non-operated leg in either group. The relative number of type I fibers increased with skiing in IG with no change in CG. Inflammatory biomarkers, plasma lipids, and mitochondrial proteins and activity did not change. Alpine skiing is metabolically beneficial and can be used as a training modality by elderly people with TKA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Degeneration and regeneration of neuromuscular junction architecture in rat skeletal muscle fibers damaged by bupivacaine hydrochloride.

    PubMed

    Nishizawa, Tomie; Tamaki, Hiroyuki; Kasuga, Norikatsu; Takekura, Hiroaki

    2003-01-01

    We evaluated the degeneration and regeneration of neuromuscular junctions (NMJs) on the extensor digitorum longus muscle of Fischer 344 rats between 4 h and 3 weeks after bupivacaine hydrochloride (BPVC) injection, which induces muscle fiber necrosis, using histochemical staining by acetylcholine esterase (AchE)-silver and electron microscopy. Degeneration of muscle fibers and NMJs was observed 4 h after BPVC injection. One week after BPVC injection, some terminal axons were almost completely retracted, and the level of basal lamina-associated AchE in some NMJ regions had gradually disappeared. At that time, the depression contained a few, mostly pit-like or elongated oval invaginations: the incipient junctional folds and some NMJs did not have any secondary junctional fold. By 2 weeks after the BPVC injection, secondary junctional folds began to develop: however, the number of secondary junctional folds was clearly less than that in normal NMJs. At 3 weeks when regeneration of muscle fibers was well advanced, the staining for AchE at the end-plates became stronger and better-defined. The volume density of mitochondria in the terminal area of the terminal significantly decreased upon BPVC-induced destruction of the NMJ, and the density reached the lowest value 24 h after BPVC injection. Significant changes in the ultrastructural features of the architecture of NMJs occurred in skeletal muscle fibers damaged by BPVC during both the degeneration and regeneration processes. The changes in the ultrastructural and morphological features of the NMJ architecture during the regeneration of degenerated muscle fibers resembled those that occur during the differentiation of normal muscle fibers.

  3. MicroRNA in Skeletal Muscle: Its Crucial Roles in Signal Proteins, Mus cle Fiber Type, and Muscle Protein Synthesis.

    PubMed

    Zhang, Jing; Liu, Yu Lan

    2017-01-01

    Pork is one of the most economical sources of animal protein for human consumption. Meat quality is an important economic trait for the swine industry, which is primarily determined by prenatal muscle development and postnatal growth. Identification of the molecular mechanisms underlying skeletal muscle development is a key priority. MicroRNAs (miRNAs) are a class of small noncoding RNAs that have emerged as key regulators of skeletal muscle development. A number of muscle-related miRNAs have been identified by functional gain and loss experiments in mouse model. However, determining miRNA-mRNA interactions involved in pig skeletal muscle still remains a significant challenge. For a comprehensive understanding of miRNA-mediated mechanisms underlying muscle development, miRNAome analyses of pig skeletal muscle have been performed by deep sequencing. Additionally, porcine miRNA single nucleotide polymorphisms have been implicated in muscle fiber types and meat quality. The present review provides an overview of current knowledge on recently identified miRNAs involved in myogenesis, muscle fiber type and muscle protein metabolism. Undoubtedly, further systematic understanding of the functions of miRNAs in pig skeletal muscle development will be helpful to expand the knowledge of basic skeletal muscle biology and be beneficial for the genetic improvement of meat quality traits. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Evidence for the load-dependent mechanical efficiency of individual myosin heads in skeletal muscle fibers activated by laser flash photolysis of caged calcium in the presence of a limited amount of ATP.

    PubMed

    Sugi, H; Iwamoto, H; Akimoto, T; Ushitani, H

    1998-03-03

    Although a contracting muscle regulates its energy output depending on the load imposed on it ("Fenn effect"), the mechanism underlying the load-dependent energy output remains obscure. To explore the possibility that the mechanical efficiency, with which chemical energy derived from ATP hydrolysis is converted into mechanical work, of individual myosin heads changes in a load-dependent manner, we examined the auxotonic shortening of glycerinated rabbit psoas muscle fibers, containing ATP molecules almost equal in number to the myosin heads, after laser-flash photolysis of caged calcium. Immediately before laser-flash activation, almost all of the myosin heads in the fiber are in the state M.ADP.Pi, and can undergo only one ATP hydrolysis cycle after activation. When the fibers were activated to shorten under various auxotonic loads, the length, force, and power output changes were found to be scaled according to the auxotonic load. Both the power and energy outputs were maximal under a moderate auxotonic load. The amount of M.ADP.Pi utilized at a time after activation was estimated from the amount of isometric force developed after interruption of fiber shortening. This amount was minimal in the isometric condition and increased nearly in proportion to the distance of fiber shortening. These results are taken as evidence that the efficiency of chemomechanical energy conversion in individual myosin heads changes in a load-dependent manner.

  5. Muscle tension line concept in nasolabial muscle complex--based on 3-dimensional reconstruction of nasolabial muscle fibers.

    PubMed

    Yin, Ningbei; Wu, Jiajun; Chen, Bo; Song, Tao; Ma, Hengyuan; Zhao, Zhenmin; Wang, Yongqian; Li, Haidong; Wu, Di

    2015-03-01

    Plastic surgeons have attempted various ways to rebuild the aesthetic subunits of the upper lip in patients with cleft lip with less than perfect results in most cases. We propose that repairing the 3 muscle tension line groups in the nasolabial complex will have improved aesthetic results. Micro-computed tomographic scans were performed on the nasolabial tissues of 5 normal aborted fetuses and used to construct a 3-dimensional model to study the nasolabial muscle complex structure. The micro-computed tomographic (CT) scans showed the close relationship and interaction between the muscle fibers of nasalis, pars peripheralis, levator labii superioris, and pars marginalis. Based on the 2-dimensional images obtained from the micro-computed tomographic scans, we suggest the concept of nasolabial muscle complex and muscle tension line group theory: there is a close relationship among the alar part of the nasalis, depressor septi muscle, orbicularis oris muscle, and levator labii superioris alaeque nasi. The tension line groups are 3 tension line structures in the nasolabial muscle complex that interlock with each other at the intersections and maintain the specific shape and aesthetics of the lip and nose.

  6. Nitric Oxide Regulates Skeletal Muscle Fatigue, Fiber Type, Microtubule Organization, and Mitochondrial ATP Synthesis Efficiency Through cGMP-Dependent Mechanisms.

    PubMed

    Moon, Younghye; Balke, Jordan E; Madorma, Derik; Siegel, Michael P; Knowels, Gary; Brouckaert, Peter; Buys, Emmanuel S; Marcinek, David J; Percival, Justin M

    2017-06-10

    Skeletal muscle nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathways are impaired in Duchenne and Becker muscular dystrophy partly because of reduced nNOSμ and soluble guanylate cyclase (GC) activity. However, GC function and the consequences of reduced GC activity in skeletal muscle are unknown. In this study, we explore the functions of GC and NO-cGMP signaling in skeletal muscle. GC1, but not GC2, expression was higher in oxidative than glycolytic muscles. GC1 was found in a complex with nNOSμ and targeted to nNOS compartments at the Golgi complex and neuromuscular junction. Baseline GC activity and GC agonist responsiveness was reduced in the absence of nNOS. Structural analyses revealed aberrant microtubule directionality in GC1 -/- muscle. Functional analyses of GC1 -/- muscles revealed reduced fatigue resistance and postexercise force recovery that were not due to shifts in type IIA-IIX fiber balance. Force deficits in GC1 -/- muscles were also not driven by defects in resting mitochondrial adenosine triphosphate (ATP) synthesis. However, increasing muscle cGMP with sildenafil decreased ATP synthesis efficiency and capacity, without impacting mitochondrial content or ultrastructure. GC may represent a new target for alleviating muscle fatigue and that NO-cGMP signaling may play important roles in muscle structure, contractility, and bioenergetics. These findings suggest that GC activity is nNOS dependent and that muscle-specific control of GC expression and differential GC targeting may facilitate NO-cGMP signaling diversity. They suggest that nNOS regulates muscle fiber type, microtubule organization, fatigability, and postexercise force recovery partly through GC1 and suggest that NO-cGMP pathways may modulate mitochondrial ATP synthesis efficiency. Antioxid. Redox Signal. 26, 966-985.

  7. Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats

    PubMed Central

    Acevedo, Luz M.; Raya, Ana I.; Martínez-Moreno, Julio M.

    2017-01-01

    Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats. PMID:28253314

  8. Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats.

    PubMed

    Acevedo, Luz M; Raya, Ana I; Martínez-Moreno, Julio M; Aguilera-Tejero, Escolástico; Rivero, José-Luis L

    2017-01-01

    Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats.

  9. Biochemical adaptations of antigravity muscle fibers to disuse atrophy

    NASA Technical Reports Server (NTRS)

    Booth, F. W.

    1978-01-01

    Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.

  10. Active shortening protects against stretch-induced force deficits in human skeletal muscle

    PubMed Central

    Saripalli, Anjali L.; Sugg, Kristoffer B.; Brooks, Susan V.

    2017-01-01

    Skeletal muscle contraction results from molecular interactions of myosin “crossbridges” with adjacent actin filament binding sites. The binding of myosin to actin can be “weak” or “strong,” and only strong binding states contribute to force production. During active shortening, the number of strongly bound crossbridges declines with increasing shortening velocity. Forcibly stretching a muscle that is actively shortening at high velocity results in no apparent negative consequences, whereas stretch of an isometrically (fixed-length) contracting muscle causes ultrastructural damage and a decline in force-generating capability. Our working hypothesis is that stretch-induced damage is uniquely attributable to the population of crossbridges that are strongly bound. We tested the hypothesis that stretch-induced force deficits decline as the prevailing shortening velocity is increased. Experiments were performed on permeabilized segments of individual skeletal muscle fibers obtained from human subjects. Fibers were maximally activated and allowed either to generate maximum isometric force (Fo), or to shorten at velocities that resulted in force maintenance of ≈50% Fo or ≈2% Fo. For each test condition, a rapid stretch equivalent to 0.1 × optimal fiber length was applied. Relative to prestretch Fo, force deficits resulting from stretches applied during force maintenance of 100, ≈50, and ≈2% Fo were 23.2 ± 8.6, 7.8 ± 4.2, and 0.3 ± 3.3%, respectively (means ± SD, n = 20). We conclude that stretch-induced damage declines with increasing shortening velocity, consistent with the working hypothesis that the fraction of strongly bound crossbridges is a causative factor in the susceptibility of skeletal muscle to stretch-induced damage. NEW & NOTEWORTHY Force deficits caused by stretch of contracting muscle are most severe when the stretch is applied during an isometric contraction, but prevented if the muscle is shortening at high velocity when the

  11. Controlled chaos: three-dimensional kinematics, fiber histochemistry, and muscle contractile dynamics of autotomized lizard tails.

    PubMed

    Higham, Timothy E; Lipsett, Kathryn R; Syme, Douglas A; Russell, Anthony P

    2013-01-01

    The ability to shed an appendage occurs in both vertebrates and invertebrates, often as a tactic to avoid predation. The tails of lizards, unlike most autotomized body parts of animals, exhibit complex and vigorous movements once disconnected from the body. Despite the near ubiquity of autotomy across groups of lizards and the fact that this is an extraordinary event involving the self-severing of the spinal cord, our understanding of why and how tails move as they do following autotomy is sparse. We herein explore the histochemistry and physiology of the tail muscles of the leopard gecko (Eublepharis macularius), a species that exhibits vigorous and variable tail movements following autotomy. To confirm that the previously studied tail movements of this species are generally representative of geckos and therefore suitable for in-depth muscle studies, we quantified the three-dimensional kinematics of autotomized tails in three additional species. The movements of the tails of all species were generally similar and included jumps, flips, and swings. Our preliminary analyses suggest that some species of gecko exhibit short but high-frequency movements, whereas others exhibit larger-amplitude but lower-frequency movements. We then compared the ATPase and oxidative capacity of muscle fibers and contractile dynamics of isolated muscle bundles from original tails, muscle from regenerate tails, and fast fibers from an upper limb muscle (iliofibularis) of the leopard gecko. Histochemical analysis revealed that more than 90% of the fibers in original and regenerate caudal muscles had high ATPase but possessed a superficial layer of fibers with low ATPase and high oxidative capacity. We found that contraction kinetics, isometric force, work, power output, and the oscillation frequency at which maximum power was generated were lowest in the original tail, followed by the regenerate tail and then the fast fibers of the iliofibularis. Muscle from the original tail exhibited

  12. Effects of dietary supplementation with carnosine on growth performance, meat quality, antioxidant capacity and muscle fiber characteristics in broiler chickens.

    PubMed

    Cong, Jiahui; Zhang, Lin; Li, Jiaolong; Wang, Shuhao; Gao, Feng; Zhou, Guanghong

    2017-08-01

    The effects of dietary carnosine were evaluated on the growth performance, meat quality, antioxidant capacity and muscle fiber characteristics in thigh muscle of 256 one-day-old male broilers assigned to four diets - basal diets supplemented with 0, 100, 200 or 400 mg kg -1 carnosine respectively - during a 42 day experiment. Carnosine concentration and carnosine synthase expression in thigh muscle were linearly increased (P < 0.05) and the feed/gain ratio was decreased (P < 0.05) in the starter period by carnosine addition. Dietary supplementation with carnosine resulted in linear increases in pH 45 min , redness and cohesiveness and decreases in drip loss, cooking loss, shear force and hardness (P < 0.05). Carnosine addition elevated the activities of antioxidant enzymes and reduced contents of malondialdehyde and carbonyl compounds (P < 0.05). Dietary carnosine linearly decreased diameters and increased densities of muscle fibers (P < 0.01). The ratios of myosin heavy chain (MyHC) I and IIa were increased while that of MyHC IIb was decreased (P < 0.01). The mRNA expressions of genes related to fiber type transformation were linearly up-regulated (P < 0.05). These findings indicated that carnosine supplementation was beneficial to improve the growth performance, meat quality, antioxidant capacity and muscle fiber characteristics of broilers. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  13. On simulating sustained isometric muscle fatigue: a phenomenological model considering different fiber metabolisms.

    PubMed

    Grasa, J; Sierra, M; Muñoz, M J; Soteras, F; Osta, R; Calvo, B; Miana-Mena, F J

    2014-11-01

    The present study shows a new computational FEM technique to simulate the evolution of the mechanical response of 3D muscle models subjected to fatigue. In an attempt to obtain very realistic models, parameters needed to adjust the mathematical formulation were obtained from in vivo experimental tests. The fatigue contractile properties of three different rat muscles (Tibialis Anterior, Extensor Digitorium Longus and Soleus) subjected to sustained maximal isometric contraction were determined. Experiments were conducted on three groups [Formula: see text] of male Wistar rats [Formula: see text] using a protocol previously developed by the authors for short tetanic contractions. The muscles were subjected to an electrical stimulus to achieve tetanic contraction during 10 s. The parameters obtained for each muscle were incorporated into a finite strain formulation for simulating active and passive behavior of muscles with different fiber metabolisms. The results show the potential of the model to predict muscle fatigue under high-frequency stimulation and the 3D distribution of mechanical variables such as stresses and strains.

  14. Does metabosensitive afferent fibers activity differ from slow- and fast-twitch muscles?

    PubMed

    Caron, Guillaume; Decherchi, Patrick; Marqueste, Tanguy

    2015-09-01

    This study was designed to investigate the metabosensitive afferent response evoked by electrically induced fatigue (EIF), lactic acid (LA) and potassium chloride (KCl) in three muscle types. We recorded the activity of groups III-IV afferents originating from soleus, gastrocnemius and tibialis anterior muscles. Our data showed a same pattern of response in the three muscles after chemical injections, i.e., a bell curve with maximal discharge rate at 1 mM for LA injections and a linear relationship between KCl concentrations and the afferent discharge rate. Furthermore, a stronger response was recorded after EIF in the gastrocnemius muscle compared to the two other muscles. The change in afferent discharge after 1 mM LA injection was higher for the gastrocnemius muscle compared to the response obtained with the corresponding concentration applied in the two other muscles, whereas changes to KCl injections did not dramatically differ between the three muscles. We conclude that anatomical (mass, phenotype, vascularization, receptor and afferent density…) and functional (flexor vs. extensor) differences between muscles could explain the amplitude of these responses.

  15. Rod distribution and muscle fiber type modification in the progression of nemaline myopathy.

    PubMed

    Gurgel-Giannetti, Juliana; Reed, Umbertina C; Marie, Sueli K; Zanoteli, Edmar; Fireman, Moacir A T; Oliveira, Acary S B; Werneck, Lineu C; Beggs, Alan H; Zatz, Mayana; Vainzof, Mariz

    2003-03-01

    Nemaline myopathy is a structural congenital myopathy associated with the presence of rodlike structures inside the muscle fibers and type I predominance. It may be caused by mutations in at least five genes: slow alpha-tropomyosin 3 (chromosome 1q22-23), nebulin (chromosome 2q21.1-q22), actin (chromosome 1q42), tropomyosin 2 (chromosome 9p13), and troponin T1 (chromosome 19q13.4). The effect of these mutations in the expression of the protein and the mechanism of rod formation is still under investigation. We analyzed the possibility of progressive alterations with time and/or disease evolution, such as transformation of type I to type II fiber and rod pattern and distribution in muscle fibers from patients with nemaline myopathy, through a morphometric and immunohistochemical analysis of different muscle protein isoforms. A tendency of diffuse rods to be organized in the subsarcolemmal region was observed in two patients who were submitted to subsequent biopsies after 10 and 13 years. Additionally, we observed the expression of type II protein isoforms in type I fibers and a higher proportion of type II fibers in the younger patient of a pair of affected sibs, giving further support to the hypothesis of progressive conversion of type II to type I fibers in nemaline myopathy.

  16. Carnitine supplementation to obese Zucker rats prevents obesity-induced type II to type I muscle fiber transition and favors an oxidative phenotype of skeletal muscle

    PubMed Central

    2013-01-01

    Background In the present study, we tested the hypothesis that carnitine supplementation counteracts obesity-induced muscle fiber transition from type I to type II. Methods 24 obese Zucker rats were randomly divided into two groups of 12 rats each (obese control, obese carnitine) and 12 lean Zucker rats were selected for lean control group. A control diet was given to both control groups and a carnitine supplemented diet (3 g/kg diet) was given to obese carnitine group for 4 wk. Components of the muscle fiber transformation in skeletal muscle were examined. Results The plasma level of carnitine were lower in the obese control group compared to the lean control group and higher in the obese carnitine group than in the other groups (P < 0.05). Plasma concentrations of triglycerides and non-esterified fatty acids were increased in obese animals compared to lean animals and the obese carnitine group had lower level compared to the obese control group (P < 0.05). The obese carnitine group had an increased number of type I muscle fibers and higher mRNA levels of type I fiber-specific myosin heavy chain, regulators of muscle fiber transition and of genes involved in carnitine uptake, fatty acid transport, β-oxidation, angiogenesis, tricarboxylic acid cycle and thermo genesis in M. rectus femoris compared to the other groups (P < 0.05). Conclusion The results demonstrate that carnitine supplementation to obese Zucker a rat counteracts the obesity-induced muscle fiber transition and restores the muscle oxidative metabolic phenotype. Carnitine supplementation is supposed to be beneficial for the treatment of elevated levels of plasma lipids during obesity or diabetes. PMID:23842456

  17. Gene regulation mediating fiber-type transformation in skeletal muscle cells is partly glucose- and ChREBP-dependent.

    PubMed

    Hanke, Nina; Scheibe, Renate J; Manukjan, Georgi; Ewers, David; Umeda, Patrick K; Chang, Kin-Chow; Kubis, Hans-Peter; Gros, Gerolf; Meissner, Joachim D

    2011-03-01

    Adaptations in the oxidative capacity of skeletal muscle cells can occur under several physiological or pathological conditions. We investigated the effect of increasing extracellular glucose concentration on the expression of markers of energy metabolism in primary skeletal muscle cells and the C2C12 muscle cell line. Growth of myotubes in 25mM glucose (high glucose, HG) compared with 5.55mM led to increases in the expression and activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a marker of glycolytic energy metabolism, while oxidative markers peroxisome proliferator-activated receptor γ coactivator 1α and citrate synthase decreased. HG induced metabolic adaptations as are seen during a slow-to-fast fiber transformation. Furthermore, HG increased fast myosin heavy chain (MHC) IId/x but did not change slow MHCI/β expression. Protein phosphatase 2A (PP2A) was shown to mediate the effects of HG on GAPDH and MHCIId/x. Carbohydrate response element-binding protein (ChREBP), a glucose-dependent transcription factor downstream of PP2A, partially mediated the effects of glucose on metabolic markers. The glucose-induced increase in PP2A activity was associated with an increase in p38 mitogen-activated protein kinase activity, which presumably mediates the increase in MHCIId/x promoter activity. Liver X receptor, another possible mediator of glucose effects, induced only an incomplete metabolic shift, mainly increasing the expression of the glycolytic marker. Taken together, HG induces a partial slow-to-fast transformation comprising metabolic enzymes together with an increased expression of MHCIId/x. This work demonstrates a functional role for ChREBP in determining the metabolic type of muscle fibers and highlights the importance of glucose as a signaling molecule in muscle. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Androgen signaling in myocytes contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue.

    PubMed

    Ophoff, Jill; Van Proeyen, Karen; Callewaert, Filip; De Gendt, Karel; De Bock, Katrien; Vanden Bosch, An; Verhoeven, Guido; Hespel, Peter; Vanderschueren, Dirk

    2009-08-01

    Muscle frailty is considered a major cause of disability in the elderly and chronically ill. However, the exact role of androgen receptor (AR) signaling in muscle remains unclear. Therefore, a postmitotic myocyte-specific AR knockout (mARKO) mouse model was created and investigated together with a mouse model with ubiquitous AR deletion. Muscles from mARKO mice displayed a marked reduction in AR protein (60-88%). Interestingly, body weights and lean body mass were lower in mARKO vs. control mice (-8%). The weight of the highly androgen-sensitive musculus levator ani was significantly reduced (-46%), whereas the weights of other peripheral skeletal muscles were not or only slightly reduced. mARKO mice had lower intra-abdominal fat but did not demonstrate a cortical or trabecular bone phenotype, indicating that selective ablation of the AR in myocytes affected male body composition but not skeletal homeostasis. Furthermore, muscle contractile performance in mARKO mice did not differ from their controls. Myocyte-specific AR ablation resulted in a conversion of fast toward slow fibers, without affecting muscle strength or fatigue. Similar results were obtained in ubiquitous AR deletion, showing lower body weight, whereas some but not all muscle weights were reduced. The percent slow fibers was increased, but no changes in muscle strength or fatigue could be detected. Together, our findings show that myocyte AR signaling contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue. The levator ani weight remains the most sensitive and specific marker of AR-mediated anabolic action on muscle.

  19. Alteration of muscle fiber characteristics and the AMPK-SIRT1-PGC-1α axis in skeletal muscle of growing pigs fed low-protein diets with varying branched-chain amino acid ratios

    PubMed Central

    Duan, Yehui; Li, Fengna; Wang, Wenlong; Guo, Qiuping; Wen, Chaoyue; Yin, Yulong

    2017-01-01

    There mainly exists four major myosin heavy chains (MyHC) (i.e., I, IIa, IIx, and IIb) in growing pigs. The current study aimed to explore the effects of low-protein diets supplemented with varying branched-chain amino acids (BCAAs) on muscle fiber characteristics and the AMPK-SIRT1-PGC-1α axis in skeletal muscles. Forty growing pigs (9.85 ± 0.35 kg) were allotted to 5 groups and fed with diets supplemented with varying leucine: isoleucine: valine ratios: 1:0.51:0.63 (20% crude protein, CP), 1:1:1 (17% CP), 1:0.75:0.75 (17% CP), 1:0.51:0.63 (17% CP), and 1:0.25:0.25 (17% CP), respectively. The skeletal muscles of different muscle fiber composition, that is, longissimus dorsi muscle (LM, a fast-twitch glycolytic muscle), biceps femoris muscle (BM, a mixed slow- and fast-twitch oxido-glycolytic muscle), and psoas major muscle (PM, a slow-twitch oxidative muscle) were collected and analyzed. Results showed that relative to the control group (1:0.51:0.63, 20% CP), the low-protein diets with the leucine: isoleucine: valine ratio ranging from 1:0.75:0.75 to 1:0.25:0.25 especially augmented the mRNA and protein abundance of MyHC I fibers in BM and lowered the mRNA abundance of MyHC IIb particularly in LM (P < 0.05), with a concurrent increase in the activation of AMPK and the mRNA abundance of SIRT and PGC-1α in BM (P < 0.05). The results reveal that low-protein diets supplemented with optimal BCAA ratio, i.e. 1:0.75:0.75-1:0.25:0.25, induce muscle more oxidative especially in oxido-glycolytic skeletal muscle of growing pigs. These effects are likely associated with the activation of the AMPK-SIRT1-PGC-1α axis. PMID:29291007

  20. Localization of survival motor neuron protein in human apoptotic-like and regenerating muscle fibers, and neuromuscular junctions.

    PubMed

    Broccolini, A; Engel, W K; Askanas, V

    1999-06-03

    Mutations in the gene encoding survival motor neuron (SMN) protein are found in > 98% of patients with autosomal-recessive spinal muscular atrophy. We investigated the possible role of SMN in normal and abnormal human muscle by immunostaining biopsies of 20 patients with various neuromuscular diseases using monoclonal antibodies against SMN. SMN was strongly expressed cytoplasmically in chronic peripheral neuropathies, in about 80% of chronically denervated, very atrophic muscle fibers containing clumps of TUNEL-positive pyknotic nuclei: about 60% of those fibers also had cytoplasmic Bcl-2 and Bax immunoreactivity. In regenerating muscle fibers of various myopathies SMN co-localized with desmin, Bcl-2 and Bax; it was also present at the postsynaptic domain of normal human neuromuscular junctions. Thus, SMN may play a role in normal and pathological processes of adult human muscle fibers.

  1. Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition

    PubMed Central

    Haizlip, K. M.; Harrison, B. C.

    2015-01-01

    Previous studies have identified over 3,000 genes that are differentially expressed in male and female skeletal muscle. Here, we review the sex-based differences in skeletal muscle fiber composition, myosin heavy chain expression, contractile function, and the regulation of these physiological differences by thyroid hormone, estrogen, and testosterone. The findings presented lay the basis for the continued work needed to fully understand the skeletal muscle differences between males and females. PMID:25559153

  2. Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle

    PubMed Central

    Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

    2015-01-01

    The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity. PMID:26485650

  3. Long-Term Effects of Botulinum Toxin Complex Type A Injection on Mechano- and Metabo-Sensitive Afferent Fibers Originating from Gastrocnemius Muscle.

    PubMed

    Caron, Guillaume; Marqueste, Tanguy; Decherchi, Patrick

    2015-01-01

    The aim of the present study was to investigate long term effects of motor denervation by botulinum toxin complex type A (BoNT/A) from Clostridium Botulinum, on the afferent fibers originating from the gastrocnemius muscle of rats. Animals were divided in 2 experimental groups: 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle, the latter being itself divided into 3 subgroups according to their locomotor recovery with the help of a test based on footprint measurements of walking rats: i) no recovery (B0), ii) 50% recovery (B50) and iii) full recovery (B100). Then, muscle properties, metabosensitive afferent fiber responses to potassium chloride (KCl) and lactic acid injections and Electrically-Induced Fatigue (EIF), and mechanosensitive responses to tendon vibrations were measured. At the end of the experiment, rats were killed and the toxin injected muscles were weighted. After toxin injection, we observed a complete paralysis associated to a loss of force to muscle stimulation and a significant muscle atrophy, and a return to baseline when the animals recover. The response to fatigue was only decreased in the B0 group. The responses to KCl injections were only altered in the B100 groups while responses to lactic acid were altered in the 3 injected groups. Finally, our results indicated that neurotoxin altered the biphasic pattern of response of the mechanosensitive fiber to tendon vibrations in the B0 and B50 groups. These results indicated that neurotoxin injection induces muscle afferent activity alterations that persist and even worsen when the muscle has recovered his motor activity.

  4. Hypertrophic cardiomyopathy mutation in cardiac troponin T (R95H) attenuates length-dependent activation in guinea pig cardiac muscle fibers.

    PubMed

    Mickelson, Alexis V; Chandra, Murali

    2017-12-01

    The central region of cardiac troponin T (TnT) is important for modulating the dynamics of muscle length-mediated cross-bridge recruitment. Therefore, hypertrophic cardiomyopathy mutations in the central region may affect cross-bridge recruitment dynamics to alter myofilament Ca 2+ sensitivity and length-dependent activation of cardiac myofilaments. Given the importance of the central region of TnT for cardiac contractile dynamics, we studied if hypertrophic cardiomyopathy-linked mutation (TnT R94H )-induced effects on contractile function would be differently modulated by sarcomere length (SL). Recombinant wild-type TnT (TnT WT ) and the guinea pig analog of the human R94H mutation (TnT R95H ) were reconstituted into detergent-skinned cardiac muscle fibers from guinea pigs. Steady-state and dynamic contractile measurements were made at short and long SLs (1.9 and 2.3 µm, respectively). Our results demonstrated that TnT R95H increased pCa 50 (-log of free Ca 2+ concentration) to a greater extent at short SL; TnT R95H increased pCa 50 by 0.11 pCa units at short SL and 0.07 pCa units at long SL. The increase in pCa 50 associated with an increase in SL from 1.9 to 2.3 µm (ΔpCa 50 ) was attenuated nearly twofold in TnT R95H fibers; ΔpCa 50 was 0.09 pCa units for TnT WT fibers but only 0.05 pCa units for TnT R95H fibers. The SL dependency of rate constants of cross-bridge distortion dynamics and tension redevelopment was also blunted by TnT R95H Collectively, our observations on the SL dependency of pCa 50 and rate constants of cross-bridge distortion dynamics and tension redevelopment suggest that mechanisms underlying the length-dependent activation cardiac myofilaments are attenuated by TnT R95H NEW & NOTEWORTHY Mutant cardiac troponin T (TnT R95H ) differently affects myofilament Ca 2+ sensitivity at short and long sarcomere length, indicating that mechanisms underlying length-dependent activation are altered by TnT R95H TnT R95H enhances myofilament Ca 2

  5. Sexual dimorphism in the histologic organization of the muscle fibers in human tongue.

    PubMed

    de Campos, Deivis; Jotz, Geraldo Pereira; Heck, Layana; Xavier, Léder Leal

    2014-07-01

    Tongue movements are critical for speech, swallowing, and respiration; and tongue dysfunction could lead to dysarthria, dysphagia, and obstructive sleep apnea, respectively. Our current understanding of the contributions of specific tongue muscles (TOs) to precise movement patterns is limited. Likewise, there is still little information regarding the orientation of histologic muscle fibers of the tongue in humans, especially between men and women. Thus, the aim of this study was to compare the histologic organization in the tongue of men and women. Ten tongues were studied in human specimens obtained from necropsies (five men and five women). The muscles were analyzed using histology, and the morphometric parameters were measured using Image Pro-Plus Software (Image Pro-Plus 6.0; Media Cybernetics, Silver Spring, MD). Slices were obtained from the anterior, median, and posterior parts of the tongue. We classified and estimated the percentages of transverse (T), oblique (O), and longitudinal (L) fibers in the tongue. To quantify the percentage of fibers in each category in the tongue, the shape coefficient (Shape Z) was estimated. Statistical differences were found between the orientation of the muscle fibers of men and women only for the middle region of the tongue. The middle region of the tongue in women compared with men has a smaller difference in the variation of the percentage of fibers T (P=0.0004), O (P=0.0006), and L (P=0.0013). These morphologic findings are probably related to physiological differences. Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  6. The relationships among jaw-muscle fiber architecture, jaw morphology, and feeding behavior in extant apes and modern humans.

    PubMed

    Taylor, Andrea B; Vinyard, Christopher J

    2013-05-01

    The jaw-closing muscles are responsible for generating many of the forces and movements associated with feeding. Muscle physiologic cross-sectional area (PCSA) and fiber length are two architectural parameters that heavily influence muscle function. While there have been numerous comparative studies of hominoid and hominin craniodental and mandibular morphology, little is known about hominoid jaw-muscle fiber architecture. We present novel data on masseter and temporalis internal muscle architecture for small- and large-bodied hominoids. Hominoid scaling patterns are evaluated and compared with representative New- (Cebus) and Old-World (Macaca) monkeys. Variation in hominoid jaw-muscle fiber architecture is related to both absolute size and allometry. PCSAs scale close to isometry relative to jaw length in anthropoids, but likely with positive allometry in hominoids. Thus, large-bodied apes may be capable of generating both absolutely and relatively greater muscle forces compared with smaller-bodied apes and monkeys. Compared with extant apes, modern humans exhibit a reduction in masseter PCSA relative to condyle-M1 length but retain relatively long fibers, suggesting humans may have sacrificed relative masseter muscle force during chewing without appreciably altering muscle excursion/contraction velocity. Lastly, craniometric estimates of PCSAs underestimate hominoid masseter and temporalis PCSAs by more than 50% in gorillas, and overestimate masseter PCSA by as much as 30% in humans. These findings underscore the difficulty of accurately estimating jaw-muscle fiber architecture from craniometric measures and suggest models of fossil hominin and hominoid bite forces will be improved by incorporating architectural data in estimating jaw-muscle forces. Copyright © 2013 Wiley Periodicals, Inc.

  7. The miRNA Transcriptome Directly Reflects the Physiological and Biochemical Differences between Red, White, and Intermediate Muscle Fiber Types

    PubMed Central

    Ma, Jideng; Wang, Hongmei; Liu, Rui; Jin, Long; Tang, Qianzi; Wang, Xun; Jiang, Anan; Hu, Yaodong; Li, Zongwen; Zhu, Li; Li, Ruiqiang; Li, Mingzhou; Li, Xuewei

    2015-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that can regulate their target genes at the post-transcriptional level. Skeletal muscle comprises different fiber types that can be broadly classified as red, intermediate, and white. Recently, a set of miRNAs was found expressed in a fiber type-specific manner in red and white fiber types. However, an in-depth analysis of the miRNA transcriptome differences between all three fiber types has not been undertaken. Herein, we collected 15 porcine skeletal muscles from different anatomical locations, which were then clearly divided into red, white, and intermediate fiber type based on the ratios of myosin heavy chain isoforms. We further illustrated that three muscles, which typically represented each muscle fiber type (i.e., red: peroneal longus (PL), intermediate: psoas major muscle (PMM), white: longissimus dorsi muscle (LDM)), have distinct metabolic patterns of mitochondrial and glycolytic enzyme levels. Furthermore, we constructed small RNA libraries for PL, PMM, and LDM using a deep sequencing approach. Results showed that the differentially expressed miRNAs were mainly enriched in PL and played a vital role in myogenesis and energy metabolism. Overall, this comprehensive analysis will contribute to a better understanding of the miRNA regulatory mechanism that achieves the phenotypic diversity of skeletal muscles. PMID:25938964

  8. Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C2C12 skeletal muscle cells.

    PubMed

    Zebedin, Eva; Sandtner, Walter; Galler, Stefan; Szendroedi, Julia; Just, Herwig; Todt, Hannes; Hilber, Karlheinz

    2004-08-01

    Each skeletal muscle of the body contains a unique composition of "fast" and "slow" muscle fibers, each of which is specialized for certain challenges. This composition is not static, and the muscle fibers are capable of adapting their molecular composition by altered gene expression (i.e., fiber type conversion). Whereas changes in the expression of contractile proteins and metabolic enzymes in the course of fiber type conversion are well described, little is known about possible adaptations in the electrophysiological properties of skeletal muscle cells. Such adaptations may involve changes in the expression and/or function of ion channels. In this study, we investigated the effects of fast-to-slow fiber type conversion on currents via voltage-gated Na+ channels in the C(2)C(12) murine skeletal muscle cell line. Prolonged treatment of cells with 25 nM of the Ca2+ ionophore A-23187 caused a significant shift in myosin heavy chain isoform expression from the fast toward the slow isoform, indicating fast-to-slow fiber type conversion. Moreover, Na+ current inactivation was significantly altered. Slow inactivation less strongly inhibited the Na+ currents of fast-to-slow fiber type-converted cells. Compared with control cells, the Na+ currents of converted cells were more resistant to block by tetrodotoxin, suggesting enhanced relative expression of the cardiac Na+ channel isoform Na(v)1.5 compared with the skeletal muscle isoform Na(v)1.4. These results imply that fast-to-slow fiber type conversion of skeletal muscle cells involves functional adaptation of their electrophysiological properties.

  9. Effect of strain on actomyosin kinetics in isometric muscle fibers.

    PubMed

    Siththanandan, V B; Donnelly, J L; Ferenczi, M A

    2006-05-15

    Investigations were conducted into the biochemical and mechanical states of cross-bridges during isometric muscle contraction. Rapid length steps (3 or 6 nm hs(-1)) were applied to rabbit psoas fibers, permeabilized and isometric, at either 12 degrees C or 20 degrees C. Fibers were activated by photolysis of P(3)-1-(2-nitrophenyl)-ethyl ester of ATP infused into rigor fibers at saturating Ca(2+). Sarcomere length, tension, and phosphate release were recorded-the latter using the MDCC-PBP fluorescent probe. A reduction in strain, induced by a rapid release step, produced a short-lived acceleration of phosphate release. Rates of the phosphate transient and that of phases 3 and 4 of tension recovery were unaffected by step size but were elevated at higher temperatures. In contrast the amplitude of the phosphate transient was smaller at 20 degrees C than 12 degrees C. The presence of 0.5 or 1.0 mM added ADP during a release step reduced both the rate of tension recovery and the poststep isometric tension. A kinetic scheme is presented to simulate the observed data and to precisely determine the rate constants for the elementary steps of the ATPase cycle.

  10. Muscle fiber type-specific response of Hsp70 expression in human quadriceps following acute isometric exercise.

    PubMed

    Tupling, A R; Bombardier, E; Stewart, R D; Vigna, C; Aqui, A E

    2007-12-01

    To investigate the time course of fiber type-specific heat shock protein 70 (Hsp70) expression in human skeletal muscle after acute exercise, 10 untrained male volunteers performed single-legged isometric knee extensor exercise at 60% of their maximal voluntary contraction (MVC) with a 50% duty cycle (5-s contraction and 5-s relaxation) for 30 min. Muscle biopsies were collected from the vastus lateralis before (Pre) exercise in the rested control leg (C) and immediately after exercise (Post) in the exercised leg (E) only and on recovery days 1 (R1), 2 (R2), 3 (R3), and 6 (R6) from both legs. As demonstrated by Western blot analysis, whole muscle Hsp70 content was unchanged (P > 0.05) immediately after exercise (Pre vs. Post), was increased (P < 0.05) by approximately 43% at R1, and remained elevated throughout the entire recovery period in E only. Hsp70 expression was also assessed in individual muscle fiber types I, IIA, and IIAX/IIX by immunohistochemistry. There were no fiber type differences (P > 0.05) in basal Hsp70 expression. Immediately after exercise, Hsp70 expression was increased (P < 0.05) in type I fibers by approximately 87% but was unchanged (P > 0.05) in type II fibers (Pre vs. Post). At R1 and throughout recovery, Hsp70 content in E was increased above basal levels (P < 0.05) in all fiber types, but Hsp70 expression was always highest (P < 0.05) in type I fibers. Hsp70 content in C was not different from Pre at any time throughout recovery. Glycogen depletion was observed at Post in all type II, but not type I, fibers, suggesting that the fiber type differences in exercise-induced Hsp70 expression were not related to glycogen availability. These results demonstrate that the time course of exercise-induced Hsp70 expression in human skeletal muscle is fiber type specific.

  11. Localized nuclear and perinuclear Ca(2+) signals in intact mouse skeletal muscle fibers.

    PubMed

    Georgiev, Tihomir; Svirin, Mikhail; Jaimovich, Enrique; Fink, Rainer H A

    2015-01-01

    Nuclear Ca(2+) is important for the regulation of several nuclear processes such as gene expression. Localized Ca(2+) signals (LCSs) in skeletal muscle fibers of mice have been mainly studied as Ca(2+) release events from the sarcoplasmic reticulum. Their location with regard to cell nuclei has not been investigated. Our study is based on the hypothesis that LCSs associated with nuclei are present in skeletal muscle fibers of adult mice. Therefore, we carried out experiments addressing this question and we found novel Ca(2+) signals associated with nuclei of skeletal muscle fibers (with possibly attached satellite cells). We measured localized nuclear and perinuclear Ca(2+) signals (NLCSs and PLCSs) alongside cytosolic localized Ca(2+) signals (CLCSs) during a hypertonic treatment. We also observed NLCSs under isotonic conditions. The NLCSs and PLCSs are Ca(2+) signals in the range of micrometer [FWHM (full width at half maximum): 2.75 ± 0.27 μm (NLCSs) and 2.55 ± 0.17 μm (PLCSs), S.E.M.]. Additionally, global nuclear Ca(2+) signals (NGCSs) were observed. To investigate which type of Ca(2+) channels contribute to the Ca(2+) signals associated with nuclei in skeletal muscle fibers, we performed measurements with the RyR blocker dantrolene, the DHPR blocker nifedipine or the IP3R blocker Xestospongin C. We observed Ca(2+) signals associated with nuclei in the presence of each blocker. Nifedipine and dantrolene had an inhibitory effect on the fraction of fibers with PLCSs. The situation for the fraction of fibers with NLCSs is more complex indicating that RyR is less important for the generation of NLCSs compared to the generation of PLCSs. The fraction of fibers with NLCSs and PLCSs is not reduced in the presence of Xestospongin C. The localized perinuclear and intranuclear Ca(2+) signals may be a powerful tool for the cell to regulate adaptive processes as gene expression. The intranuclear Ca(2+) signals may be particularly interesting in this respect.

  12. Myostatin promotes distinct responses on protein metabolism of skeletal and cardiac muscle fibers of rodents.

    PubMed

    Manfredi, L H; Paula-Gomes, S; Zanon, N M; Kettelhut, I C

    2017-10-19

    Myostatin is a novel negative regulator of skeletal muscle mass. Myostatin expression is also found in heart in a much less extent, but it can be upregulated in pathological conditions, such as heart failure. Myostatin may be involved in inhibiting protein synthesis and/or increasing protein degradation in skeletal and cardiac muscles. Herein, we used cell cultures and isolated muscles from rats to determine protein degradation and synthesis. Muscles incubated with myostatin exhibited an increase in proteolysis with an increase of Atrogin-1, MuRF1 and LC3 genes. Extensor digitorum longus muscles and C2C12 myotubes exhibited a reduction in protein turnover. Cardiomyocytes showed an increase in proteolysis by activating autophagy and the ubiquitin proteasome system, and a decrease in protein synthesis by decreasing P70S6K. The effect of myostatin on protein metabolism is related to fiber type composition, which may be associated to the extent of atrophy mediated effect of myostatin on muscle.

  13. Myostatin promotes distinct responses on protein metabolism of skeletal and cardiac muscle fibers of rodents

    PubMed Central

    Manfredi, L.H.; Paula-Gomes, S.; Zanon, N.M.; Kettelhut, I.C.

    2017-01-01

    Myostatin is a novel negative regulator of skeletal muscle mass. Myostatin expression is also found in heart in a much less extent, but it can be upregulated in pathological conditions, such as heart failure. Myostatin may be involved in inhibiting protein synthesis and/or increasing protein degradation in skeletal and cardiac muscles. Herein, we used cell cultures and isolated muscles from rats to determine protein degradation and synthesis. Muscles incubated with myostatin exhibited an increase in proteolysis with an increase of Atrogin-1, MuRF1 and LC3 genes. Extensor digitorum longus muscles and C2C12 myotubes exhibited a reduction in protein turnover. Cardiomyocytes showed an increase in proteolysis by activating autophagy and the ubiquitin proteasome system, and a decrease in protein synthesis by decreasing P70S6K. The effect of myostatin on protein metabolism is related to fiber type composition, which may be associated to the extent of atrophy mediated effect of myostatin on muscle. PMID:29069231

  14. Effect of maternal dietary restriction during pregnancy on lamb carcass characteristics and muscle fiber composition.

    PubMed

    Daniel, Z C T R; Brameld, J M; Craigon, J; Scollan, N D; Buttery, P J

    2007-06-01

    Two experiments were conducted to determine whether the decreased proportion of fast muscle fibers seen previously in 2-wk-old lambs from ewes that were dietary restricted from d 30 to 70 of gestation are still evident in older lambs and what the consequences may be in terms of growth rates and carcass composition. Throughout both experiments, ewes were fed on an individual basis according to the recommended dietary allowance throughout pregnancy relative to metabolic BW (BW(0.73)). Control groups were fed as above, and the treatment groups had their nutrient supply reduced to 50% of this recommended allowance from d 30 to 70 (Exp. 1) or d 30 to 85 (Exp. 2) of gestation, after which they were returned to the same level of nutrition as the control group. All twin lambs were kept with their dams, and at 2 wk were given access to creep. After weaning, lambs were individually housed and fed ad libitum to 24 or 17 wk of age for Exp. 1 and 2, respectively. Although not significant (P = 0.18), growth to 24 wk (Exp. 1) resulted in a small decrease in the protein content and therefore an increase in the fat:lean ratio in the carcass of lambs subjected to maternal dietary restriction. This was not apparent when animals were slaughtered at 17 wk (Exp. 2; P > 0.68). Few significant effects of maternal dietary restriction on the fiber type composition of muscles were observed. In Exp. 1 the number of fast fibers increased (P < 0.008) with no effect on slow fiber number in LM. In Exp. 2 an increase in the total number of fibers in male lambs and an increase in type II (A and B) fibers in female lambs were observed in the LM, and an increase in IIB fiber number was observed in semitendinosus (ST) muscle from male lambs. Prenatal maternal dietary restriction during the time of muscle differentiation demonstrated an increase in type IIB muscle fibers and increase in intramuscular fat; although significant, effects on subsequent carcass quality of lambs were relatively small. These

  15. Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype.

    PubMed

    Chacon-Cabrera, Alba; Mateu-Jimenez, Mercè; Langohr, Klaus; Fermoselle, Clara; García-Arumí, Elena; Andreu, Antoni L; Yelamos, Jose; Barreiro, Esther

    2017-12-01

    Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1 -/- ) and Parp-2 -/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1 -/- , and Parp-2 -/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1 -/- and Parp-2 -/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention. © 2017 Wiley Periodicals, Inc.

  16. Dietary resveratrol supplementation improves meat quality of finishing pigs through changing muscle fiber characteristics and antioxidative status.

    PubMed

    Zhang, Cheng; Luo, Junqiu; Yu, Bing; Zheng, Ping; Huang, Zhiqing; Mao, Xiangbing; He, Jun; Yu, Jie; Chen, Jiali; Chen, Daiwen

    2015-04-01

    This study investigated the effects of resveratrol (0, 300, 600 mg/kg) on meat quality, muscle fiber characteristics and antioxidative capacity of finishing pigs. The results showed that resveratrol not only increased m. longissimus dorsi (LM) pH(24 h), a*, crude protein and myoglobin content but also decreased L*(24 h), shear force, drip loss, glycolytic potential, as well as backfat depth, LM lactate dehydrogenase activity and mRNA level. Meanwhile, LM total antioxidative capacity, glutathione peroxidase activity and its mRNA level were increased by resveratrol, while malonaldehyde content was decreased. In addition, resveratrol increased myosin heavy chain (MyHC)IIa mRNA level and decreased MyHCIIb mRNA level, along with decreased myofiber cross-sectional area. In conclusion, these results suggest that resveratrol is an effective feed additive to improve pork quality, and the underlying mechanism may be partly due to the changed muscle fiber characteristics and antioxidative capacity induced by resveratrol. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Active shortening protects against stretch-induced force deficits in human skeletal muscle.

    PubMed

    Saripalli, Anjali L; Sugg, Kristoffer B; Mendias, Christopher L; Brooks, Susan V; Claflin, Dennis R

    2017-05-01

    Skeletal muscle contraction results from molecular interactions of myosin "crossbridges" with adjacent actin filament binding sites. The binding of myosin to actin can be "weak" or "strong," and only strong binding states contribute to force production. During active shortening, the number of strongly bound crossbridges declines with increasing shortening velocity. Forcibly stretching a muscle that is actively shortening at high velocity results in no apparent negative consequences, whereas stretch of an isometrically (fixed-length) contracting muscle causes ultrastructural damage and a decline in force-generating capability. Our working hypothesis is that stretch-induced damage is uniquely attributable to the population of crossbridges that are strongly bound. We tested the hypothesis that stretch-induced force deficits decline as the prevailing shortening velocity is increased. Experiments were performed on permeabilized segments of individual skeletal muscle fibers obtained from human subjects. Fibers were maximally activated and allowed either to generate maximum isometric force (F o ), or to shorten at velocities that resulted in force maintenance of ≈50% F o or ≈2% F o For each test condition, a rapid stretch equivalent to 0.1 × optimal fiber length was applied. Relative to prestretch F o , force deficits resulting from stretches applied during force maintenance of 100, ≈50, and ≈2% F o were 23.2 ± 8.6, 7.8 ± 4.2, and 0.3 ± 3.3%, respectively (means ± SD, n = 20). We conclude that stretch-induced damage declines with increasing shortening velocity, consistent with the working hypothesis that the fraction of strongly bound crossbridges is a causative factor in the susceptibility of skeletal muscle to stretch-induced damage. NEW & NOTEWORTHY Force deficits caused by stretch of contracting muscle are most severe when the stretch is applied during an isometric contraction, but prevented if the muscle is shortening at high velocity when the stretch

  18. Supersonic Shear Imaging Elastography in Skeletal Muscles: Relationship Between In Vivo and Synthetic Fiber Angles and Shear Modulus.

    PubMed

    Lima, Kelly; Rouffaud, Remi; Pereira, Wagner; Oliveira, Liliam F

    2018-04-30

    To verify a relationship between the pennation angle of synthetic fibers and muscle fibers with the shear modulus (μ) generated by Supersonic shear imaging (SSI) elastography and to compare the anisotropy of synthetic and in vivo pennate muscle fibers in the x 2 -x 3 plane (probe perpendicular to water surface or skin). First, the probe of Aixplorer ultrasound scanner (v.9, Supersonic Imagine, Aix-en-Provence, France) was placed in 2 positions (parallel [aligned] and transverse to the fibers) to test the anisotropy in the x 2 -x 3 plane. Subsequently, it was inclined (x 1 -x 3 plane) in relation to the fibers, forming 3 angles (18.25 °, 21.55 °, 36.86 °) for synthetic fibers and one (approximately 0 °) for muscle fibers. On the x 2 -x 3 plane, μ values of the synthetic and vastus lateralis fibers were significantly lower (P < .0001) at the transverse probe position than the longitudinal one. In the x 1 -x 3 plane, the μ values were significantly reduced (P < .0001) with the probe angle increasing, only for the synthetic fibers (approximately 0.90 kPa for each degree of pennation angle). The pennation angle was not related to the μ values generated by SSI elastography for the in vivo lateral head of the gastrocnemius and vastus lateralis muscles. However, a μ reduction with an angle increase in the synthetic fibers was observed. These findings contribute to increasing the applicability of SSI in distinct muscle architecture at normal or pathologic conditions. © 2018 by the American Institute of Ultrasound in Medicine.

  19. Decreased specific force and power production of muscle fibers from myostatin-deficient mice are associated with a suppression of protein degradation.

    PubMed

    Mendias, Christopher L; Kayupov, Erdan; Bradley, Joshua R; Brooks, Susan V; Claflin, Dennis R

    2011-07-01

    Myostatin (MSTN) is a member of the transforming growth factor-β superfamily of cytokines and is a negative regulator of skeletal muscle mass. Compared with MSTN(+/+) mice, the extensor digitorum longus muscles of MSTN(-/-) mice exhibit hypertrophy, hyperplasia, and greater maximum isometric force production (F(o)), but decreased specific maximum isometric force (sF(o); F(o) normalized by muscle cross-sectional area). The reason for the reduction in sF(o) was not known. Studies in myotubes indicate that inhibiting myostatin may increase muscle mass by decreasing the expression of the E3 ubiquitin ligase atrogin-1, which could impact the force-generating capacity and size of muscle fibers. To gain a greater understanding of the influence of myostatin on muscle contractility, we determined the impact of myostatin deficiency on the contractility of permeabilized muscle fibers and on the levels of atrogin-1 and ubiquitinated myosin heavy chain in whole muscle. We hypothesized that single fibers from MSTN(-/-) mice have a greater F(o), but no difference in sF(o), and a decrease in atrogin-1 and ubiquitin-tagged myosin heavy chain levels. The results indicated that fibers from MSTN(-/-) mice have a greater cross-sectional area, but do not have a greater F(o) and have a sF(o) that is significantly lower than fibers from MSTN(+/+) mice. The extensor digitorum longus muscles from MSTN(-/-) mice also have reduced levels of atrogin-1 and ubiquitinated myosin heavy chain. These findings suggest that myostatin inhibition in otherwise healthy muscle increases the size of muscle fibers and decreases atrogin-1 levels, but does not increase the force production of individual muscle fibers.

  20. Effect of temperature on residual force enhancement in single skeletal muscle fibers.

    PubMed

    Lee, Eun-Jeong; Herzog, Walter

    2008-08-28

    It is well accepted that the steady-state isometric force following active stretching of a muscle is greater than the steady-state isometric force obtained in a purely isometric contraction at the same length. This property of skeletal muscle has been called residual force enhancement (FE). Despite decades of research the mechanisms responsible for FE have remained largely unknown. Based on previous studies showing increases in FE in fibers in which cross-bridges were biased towards weakly bound states, we hypothesized that FE might be associated with a stretch-induced facilitation of transitioning from weakly to strongly bound cross-bridges. In order to test this hypothesis, single fibers (n=11) from the lumbrical muscles of frog (Rana pipiens) were used to determine FE at temperatures of 7 and 20 degrees C. At the cold temperature, cross-bridges are biased towards weakly bound states, therefore we expected FE to be greater at 7 degrees C compared to 20 degrees C. The average FE was significantly greater at 7 degrees C (11.5+/-1.1%) than at 20 degrees C (7.8+/-1.0%), as expected. The enhancement of force/stiffness was also significantly greater at the low (13.3+/-1.4%) compared to the high temperature (5.6+/-1.7%), indicating an increased conversion from weakly to strongly bound cross-bridges at the low temperature. We conclude from the results of this study that muscle preparations that are biased towards weakly bound cross-bridge states show increased FE for given stretch conditions, thereby supporting the idea that FE might be caused, in part, by a stretch-induced facilitation of the conversion of weakly to strongly bound cross-bridges.

  1. Clustering of the human skeletal muscle fibers using linear programming and angular Hilbertian metrics.

    PubMed

    Neji, Radhouène; Besbes, Ahmed; Komodakis, Nikos; Deux, Jean-François; Maatouk, Mezri; Rahmouni, Alain; Bassez, Guillaume; Fleury, Gilles; Paragios, Nikos

    2009-01-01

    In this paper, we present a manifold clustering method fo the classification of fibers obtained from diffusion tensor images (DTI) of the human skeletal muscle. Using a linear programming formulation of prototype-based clustering, we propose a novel fiber classification algorithm over manifolds that circumvents the necessity to embed the data in low dimensional spaces and determines automatically the number of clusters. Furthermore, we propose the use of angular Hilbertian metrics between multivariate normal distributions to define a family of distances between tensors that we generalize to fibers. These metrics are used to approximate the geodesic distances over the fiber manifold. We also discuss the case where only geodesic distances to a reduced set of landmark fibers are available. The experimental validation of the method is done using a manually annotated significant dataset of DTI of the calf muscle for healthy and diseased subjects.

  2. Skeletal muscle growth and fiber composition in mice are regulated through the transcription factors STAT5a/b: linking growth hormone to the androgen receptor.

    PubMed

    Klover, Peter; Chen, Weiping; Zhu, Bing-Mei; Hennighausen, Lothar

    2009-09-01

    In skeletal muscle, STAT5a/b transcription factors are critical for normal postnatal growth, whole-animal glucose homeostasis, and local IGF-1 production. These observations have led us to hypothesize that STAT5a/b are critical for maintenance of normal muscle mass and function. To investigate this, mice with a skeletal muscle-specific deletion of the Stat5a/b genes (Stat5MKO) were used. Stat5MKO mice displayed reduced muscle mass, altered fiber-type distribution and reduced activity. On a molecular level, gene expression in skeletal muscle of Stat5MKO and control mice was analyzed by microarrays and real-time PCR, both in the presence and absence of growth hormone (GH) stimulation. Expression of several genes involved in muscle growth and fiber type were significantly changed. Specifically, in the quadriceps, a muscle almost exclusively composed of type II fibers, the absence of STAT5a/b led to increased expression of several genes associated with type I fibers and the de novo appearance of type I fibers. In addition, it is shown here that expression of the androgen receptor gene (Ar) is controlled by GH through STAT5a/b. The link between STAT5a/b and Ar gene is likely through direct transcriptional regulation, as chromatin immunoprecipitaion of the Ar promoter region in C2C12 myoblasts was accomplished by antibodies against STAT5a. These experiments demonstrate an important role for STAT5a/b in skeletal muscle physiology, and they provide a direct link to androgen signaling.

  3. STRETCHY ELECTRONICS. Hierarchically buckled sheath-core fibers for superelastic electronics, sensors, and muscles.

    PubMed

    Liu, Z F; Fang, S; Moura, F A; Ding, J N; Jiang, N; Di, J; Zhang, M; Lepró, X; Galvão, D S; Haines, C S; Yuan, N Y; Yin, S G; Lee, D W; Wang, R; Wang, H Y; Lv, W; Dong, C; Zhang, R C; Chen, M J; Yin, Q; Chong, Y T; Zhang, R; Wang, X; Lima, M D; Ovalle-Robles, R; Qian, D; Lu, H; Baughman, R H

    2015-07-24

    Superelastic conducting fibers with improved properties and functionalities are needed for diverse applications. Here we report the fabrication of highly stretchable (up to 1320%) sheath-core conducting fibers created by wrapping carbon nanotube sheets oriented in the fiber direction on stretched rubber fiber cores. The resulting structure exhibited distinct short- and long-period sheath buckling that occurred reversibly out of phase in the axial and belt directions, enabling a resistance change of less than 5% for a 1000% stretch. By including other rubber and carbon nanotube sheath layers, we demonstrated strain sensors generating an 860% capacitance change and electrically powered torsional muscles operating reversibly by a coupled tension-to-torsion actuation mechanism. Using theory, we quantitatively explain the complementary effects of an increase in muscle length and a large positive Poisson's ratio on torsional actuation and electronic properties. Copyright © 2015, American Association for the Advancement of Science.

  4. Effect of ractopamine-HCl supplementation for 28 days on carcass characteristics, muscle fiber morphometrics, and whole muscle yields of six distinct muscles of the loin and round.

    PubMed

    Gonzalez, J M; Johnson, S E; Stelzleni, A M; Thrift, T A; Savell, J D; Warnock, T M; Johnson, D D

    2010-07-01

    This study evaluated the effects of ractopamine-HCl (RAC) supplementation on carcass characteristics, muscle fiber morphometrics, and tenderness. Thirty-four steers (2 groups, 4 replicates) were fed RAC or carrier for 28 days prior to harvest. Seventy-two hours postmortem, the Longissimus lumborum (LL), Gracilis (GRA), Vastus lateralis (VL), Rectus femoris (RF), Semimembranosus (SM), and Adductor (ADD) were dissected from each carcass. Commodity weight, denuded weight, and muscle dimensions were collected. RAC supplementation tended to affect dressing percentage (P=0.15) and muscle firmness (P<0.15), and significantly affected lean maturity (P<0.05) and marbling score (P<0.05). With the exception of the LL and GRA (P<0.05), RAC had no effect on muscle dimensions. RAC did not influence the tenderness of vacuum-packaged, aged steaks as measured by Warner-Bratzler shear force. Muscle fiber size within the six muscles was unchanged (P>0.05) by RAC. Thus, RAC improves carcass parameters without a negative impact on tenderness. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. Bite force estimation and the fiber architecture of felid masticatory muscles.

    PubMed

    Hartstone-Rose, Adam; Perry, Jonathan M G; Morrow, Caroline J

    2012-08-01

    Increasingly, analyses of craniodental dietary adaptations take into account mechanical properties of foods. However, masticatory muscle fiber architecture has been described for relatively few lineages, even though an understanding of the scaling of this anatomy can yield important information about adaptations for stretch and strength in the masticatory system. Data on the mandibular adductors of 28 specimens from nine species of felids representing nearly the entire body size range of the family allow us to evaluate the influence of body size and diet on the masticatory apparatus within this lineage. Masticatory muscle masses scale isometrically, tending toward positive allometry, with body mass and jaw length. This allometry becomes significant when the independent variable is a geometric mean of cranial variables. For all three body size proxies, the physiological cross-sectional area and predicted bite forces scale with significant positive allometry. Average fiber lengths (FL) tend toward negative allometry though with wide confidence intervals resulting from substantial scatter. We believe that these FL residuals are affected by dietary signals within the sample; though the mechanical properties of felid diets are relatively similar across species, the most durophagous species in our sample (the jaguar) appears to have relatively higher force production capabilities. The more notable dietary trend in our sample is the relationship between FL and relative prey size: felid species that predominantly consume relatively small prey have short masticatory muscle fibers, and species that regularly consume relatively large prey have relatively long fibers. This suggests an adaptive signal related to gape. Copyright © 2012 Wiley Periodicals, Inc.

  6. Structural alterations of thin actin filaments in muscle contraction by synchrotron X-ray fiber diffraction.

    PubMed

    Wakabayashi, Katsuzo; Sugimoto, Yasunobu; Takezawa, Yasunori; Ueno, Yutaka; Minakata, Shiho; Oshima, Kanji; Matsuo, Tatsuhito; Kobayashi, Takakazu

    2007-01-01

    Strong evidence has been accumulated that the conformational changes of the thin actin filaments are occurring and playing an important role in the entire process of muscle contraction. The conformational changes and the mechanical properties of the thin actin filaments we have found by X-ray fiber diffraction on skeletal muscle contraction are explored. Recent studies on the conformational changes of regulatory proteins bound to actin filaments upon activation and in the force generation process are also described. Finally, the roles of structural alterations and dynamics of the actin filaments are discussed in conjunction with the regulation mechanism and the force generation mechanism.

  7. The miRNA Transcriptome Directly Reflects the Physiological and Biochemical Differences between Red, White, and Intermediate Muscle Fiber Types.

    PubMed

    Ma, Jideng; Wang, Hongmei; Liu, Rui; Jin, Long; Tang, Qianzi; Wang, Xun; Jiang, Anan; Hu, Yaodong; Li, Zongwen; Zhu, Li; Li, Ruiqiang; Li, Mingzhou; Li, Xuewei

    2015-04-29

    MicroRNAs (miRNAs) are small non-coding RNAs that can regulate their target genes at the post-transcriptional level. Skeletal muscle comprises different fiber types that can be broadly classified as red, intermediate, and white. Recently, a set of miRNAs was found expressed in a fiber type-specific manner in red and white fiber types. However, an in-depth analysis of the miRNA transcriptome differences between all three fiber types has not been undertaken. Herein, we collected 15 porcine skeletal muscles from different anatomical locations, which were then clearly divided into red, white, and intermediate fiber type based on the ratios of myosin heavy chain isoforms. We further illustrated that three muscles, which typically represented each muscle fiber type (i.e., red: peroneal longus (PL), intermediate: psoas major muscle (PMM), white: longissimus dorsi muscle (LDM)), have distinct metabolic patterns of mitochondrial and glycolytic enzyme levels. Furthermore, we constructed small RNA libraries for PL, PMM, and LDM using a deep sequencing approach. Results showed that the differentially expressed miRNAs were mainly enriched in PL and played a vital role in myogenesis and energy metabolism. Overall, this comprehensive analysis will contribute to a better understanding of the miRNA regulatory mechanism that achieves the phenotypic diversity of skeletal muscles.

  8. Artificial muscles of dielectric elastomers attached to artificial tendons of functionalized carbon fibers

    NASA Astrophysics Data System (ADS)

    Ye, Zhihang; Faisal, Md. Shahnewaz Sabit; Asmatulu, Ramazan; Chen, Zheng

    2014-03-01

    Dielectric elastomers are soft actuation materials with promising applications in robotics and biomedical de- vices. In this paper, a bio-inspired artificial muscle actuator with artificial tendons is developed for robotic arm applications. The actuator uses dielectric elastomer as artificial muscle and functionalized carbon fibers as artificial tendons. A VHB 4910 tape is used as the dielectric elastomer and PDMS is used as the bonding material to mechanically connect the carbon fibers to the elastomer. Carbon fibers are highly popular for their high electrical conductivities, mechanical strengths, and bio-compatibilities. After the acid treatments for the functionalization of carbon fibers (500 nm - 10 μm), one end of carbon fibers is spread into the PDMS material, which provides enough bonding strength with other dielectric elastomers, while the other end is connected to a DC power supply. To characterize the actuation capability of the dielectric elastomer and electrical conductivity of carbon fibers, a diaphragm actuator is fabricated, where the carbon fibers are connected to the actuator. To test the mechanical bonding between PDMS and carbon fibers, specimens of PDMS bonded with carbon fibers are fabricated. Experiments have been conducted to verify the actuation capability of the dielectric elastomer and mechanical bonding of PDMS with carbon fibers. The energy efficiency of the dielectric elastomer increases as the load increases, which can reach above 50%. The mechanical bonding is strong enough for robotic arm applications.

  9. Electrically controllable twisted-coiled artificial muscle actuators using surface-modified polyester fibers

    NASA Astrophysics Data System (ADS)

    Park, Jungwoo; Yoo, Ji Wang; Seo, Hee Won; Lee, Youngkwan; Suhr, Jonghwan; Moon, Hyungpil; Koo, Ja Choon; Ryeol Choi, Hyouk; Hunt, Robert; Kim, Kwang Jin; Kim, Soo Hyun; Nam, Jae-Do

    2017-03-01

    As a new class of thermally activated actuators based on polymeric fibers, we investigated polyethylene terephthalate (PET) yarns for the development of a twisted-coiled polymer fiber actuator (TCA). The PET yarn TCA exhibited the maximum linear actuation up to 8.9% by external heating at above the glass transition temperature, 160 °C-180 °C. The payload of the actuator was successfully correlated with the preload and training-load conditions by an empirical equation. Furthermore, the PET-based TCA was electrically driven by Joule heating after the PET surface was metallization with silver. For the fast and precise control of PET yarn TCA, electroless silver plating was conducted to form electrical conductive layers on the PET fiber surface. The silver plated PET-based TCA was tested by Joule heating and the tensile actuation was increased up to 12.1% (6 V) due to the enhanced surface hardness and slippage of PET fibers. Overall, silver plating of the polymeric yarn provided a fast actuation speed and enhanced actuation performance of the TCA actuator by Joule heating, providing a great potential for being used in artificial muscle for biomimetic machines including robots, industrial actuators and powered exoskeletons.

  10. A fully resolved fluid-structure-muscle-activation model for esophageal transport

    NASA Astrophysics Data System (ADS)

    Kou, Wenjun; Bhalla, Amneet P. S.; Griffith, Boyce E.; Johnson, Mark; Patankar, Neelesh A.

    2013-11-01

    Esophageal transport is a mechanical and physiological process that transfers the ingested food bolus from the pharynx to the stomach through a multi-layered esophageal tube. The process involves interactions between the bolus, esophageal wall composed of mucosal, circular muscle (CM) and longitudinal muscle (LM) layers, and neurally coordinated muscle activation including CM contraction and LM shortening. In this work, we present a 3D fully-resolved model of esophageal transport based on the immersed boundary method. The model describes the bolus as a Newtonian fluid, the esophageal wall as a multi-layered elastic tube represented by springs and beams, and the muscle activation as a traveling wave of sequential actuation/relaxation of muscle fibers, represented by springs with dynamic rest lengths. Results on intraluminal pressure profile and bolus shape will be shown, which are qualitatively consistent with experimental observations. Effects of activating CM contraction only, LM shortening only or both, for the bolus transport, are studied. A comparison among them can help to identify the role of each type of muscle activation. The support of grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

  11. Repeated high-intensity exercise modulates Ca(2+) sensitivity of human skeletal muscle fibers.

    PubMed

    Gejl, K D; Hvid, L G; Willis, S J; Andersson, E; Holmberg, H-C; Jensen, R; Frandsen, U; Hansen, J; Plomgaard, P; Ørtenblad, N

    2016-05-01

    The effects of short-term high-intensity exercise on single fiber contractile function in humans are unknown. Therefore, the purposes of this study were: (a) to access the acute effects of repeated high-intensity exercise on human single muscle fiber contractile function; and (b) to examine whether contractile function was affected by alterations in the redox balance. Eleven elite cross-country skiers performed four maximal bouts of 1300 m treadmill skiing with 45 min recovery. Contractile function of chemically skinned single fibers from triceps brachii was examined before the first and following the fourth sprint with respect to Ca(2+) sensitivity and maximal Ca(2+) -activated force. To investigate the oxidative effects of exercise on single fiber contractile function, a subset of fibers was incubated with dithiothreitol (DTT) before analysis. Ca(2+) sensitivity was enhanced by exercise in both MHC I (17%, P < 0.05) and MHC II (15%, P < 0.05) fibers. This potentiation was not present after incubation of fibers with DTT. Specific force of both MHC I and MHC II fibers was unaffected by exercise. In conclusion, repeated high-intensity exercise increased Ca(2+) sensitivity in both MHC I and MHC II fibers. This effect was not observed in a reducing environment indicative of an exercise-induced oxidation of the human contractile apparatus. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. An image processing pipeline to detect and segment nuclei in muscle fiber microscopic images.

    PubMed

    Guo, Yanen; Xu, Xiaoyin; Wang, Yuanyuan; Wang, Yaming; Xia, Shunren; Yang, Zhong

    2014-08-01

    Muscle fiber images play an important role in the medical diagnosis and treatment of many muscular diseases. The number of nuclei in skeletal muscle fiber images is a key bio-marker of the diagnosis of muscular dystrophy. In nuclei segmentation one primary challenge is to correctly separate the clustered nuclei. In this article, we developed an image processing pipeline to automatically detect, segment, and analyze nuclei in microscopic image of muscle fibers. The pipeline consists of image pre-processing, identification of isolated nuclei, identification and segmentation of clustered nuclei, and quantitative analysis. Nuclei are initially extracted from background by using local Otsu's threshold. Based on analysis of morphological features of the isolated nuclei, including their areas, compactness, and major axis lengths, a Bayesian network is trained and applied to identify isolated nuclei from clustered nuclei and artifacts in all the images. Then a two-step refined watershed algorithm is applied to segment clustered nuclei. After segmentation, the nuclei can be quantified for statistical analysis. Comparing the segmented results with those of manual analysis and an existing technique, we find that our proposed image processing pipeline achieves good performance with high accuracy and precision. The presented image processing pipeline can therefore help biologists increase their throughput and objectivity in analyzing large numbers of nuclei in muscle fiber images. © 2014 Wiley Periodicals, Inc.

  13. Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation.

    PubMed

    Wallace, Marita A; Della Gatta, Paul A; Ahmad Mir, Bilal; Kowalski, Greg M; Kloehn, Joachim; McConville, Malcom J; Russell, Aaron P; Lamon, Séverine

    2016-01-01

    Skeletal muscle growth and regeneration depend on the activation of satellite cells, which leads to myocyte proliferation, differentiation and fusion with existing muscle fibers. Skeletal muscle cell proliferation and differentiation are tightly coordinated by a continuum of molecular signaling pathways. The striated muscle activator of Rho signaling (STARS) is an actin binding protein that regulates the transcription of genes involved in muscle cell growth, structure and function via the stimulation of actin polymerization and activation of serum-response factor (SRF) signaling. STARS mediates cell proliferation in smooth and cardiac muscle models; however, whether STARS overexpression enhances cell proliferation and differentiation has not been investigated in skeletal muscle cells. We demonstrate for the first time that STARS overexpression enhances differentiation but not proliferation in C2C12 mouse skeletal muscle cells. Increased differentiation was associated with an increase in the gene levels of the myogenic differentiation markers Ckm, Ckmt2 and Myh4, the differentiation factor Igf2 and the myogenic regulatory factors (MRFs) Myf5 and Myf6. Exposing C2C12 cells to CCG-1423, a pharmacological inhibitor of SRF preventing the nuclear translocation of its co-factor MRTF-A, had no effect on myotube differentiation rate, suggesting that STARS regulates differentiation via a MRTF-A independent mechanism. These findings position STARS as an important regulator of skeletal muscle growth and regeneration.

  14. Gluteus Minimus and Gluteus Medius Muscle Activity During Common Rehabilitation Exercises in Healthy Postmenopausal Women.

    PubMed

    Ganderton, Charlotte; Pizzari, Tania; Cook, Jill; Semciw, Adam

    2017-12-01

    Study Design Controlled laboratory study, cross-sectional. Background The gluteus medius (GMed) and gluteus minimus (GMin) provide dynamic stability of the hip joint and pelvis. These muscles are susceptible to atrophy and injury in individuals during menopause, aging, and disease. Numerous studies have reported on the ability of exercises to elicit high levels of GMed activity; however, few studies have differentiated between the portions of the GMed, and none have examined the GMin. Objectives To quantify and rank the level of muscle activity of the 2 segments of the GMin (anterior and posterior fibers) and 3 segments of the GMed (anterior, middle, and posterior fibers) during 4 isometric and 3 dynamic exercises in a group of healthy, postmenopausal women. Methods Intramuscular electrodes were inserted into each segment of the GMed and GMin in 10 healthy, postmenopausal women. Participants completed 7 gluteal rehabilitation exercises, and average normalized muscle activity was used to rank the exercises from highest to lowest. Results The isometric standing hip hitch with contralateral hip swing was the highest-ranked exercise for all muscle segments except the anterior GMin, where it was ranked second. The highest-ranked dynamic exercise for all muscle segments was the dip test. Conclusion The hip hitch and its variations maximally activate the GMed and GMin muscle segments, and may be useful in hip muscle rehabilitation in postmenopausal women. J Orthop Sports Phys Ther 2017;47(12):914-922. Epub 15 Oct 2017. doi:10.2519/jospt.2017.7229.

  15. The regulation of skeletal muscle fiber-type composition by betaine is associated with NFATc1/MyoD.

    PubMed

    Du, Jingjing; Shen, Linyuan; Zhang, Peiwen; Tan, Zhendong; Cheng, Xiao; Luo, Jia; Zhao, Xue; Yang, Qiong; Gu, Hao; Jiang, An'an; Ma, Jideng; Tang, Qianzi; Jin, Long; Shuai, Surong; Li, Mingzhou; Jiang, Yanzhi; Tang, Guoqing; Bai, Lin; Li, Xuewei; Wang, Jinyong; Zhang, Shunhua; Zhu, Li

    2018-06-06

    Increasing evidence indicates that muscular dysfunction or alterations in skeletal muscle fiber-type composition not only are involved in muscle metabolism and function but also can limit functional capacity. Therefore, understanding the mechanisms regulating key events during skeletal myogenesis is necessary. Betaine is a naturally occurring component of commonly eaten foods. Here, we showed that 10 mM betaine supplementation in vitro significantly repressed myoblast proliferation and enhanced myoblast differentiation. This effect can be mediated by regulation of miR-29b-3p. Further analysis showed that betaine supplementation in vitro regulated skeletal muscle fiber-type composition through the induction of NFATc1 and the negative regulation of MyoD expression. Furthermore, mice fed with 10 mM betaine in water for 133 days showed no impairment in overall health. Consistently, betaine supplementation increased muscle mass, promoted muscle formation, and modulated the ratio of fiber types in skeletal muscle in vivo. These findings shed light on the diverse biological functions of betaine and indicate that betaine supplementation may lead to new therapies for diseases such as muscular dystrophy or other diseases related to muscle dysfunction. Betaine supplementation inhibits proliferation and promotes differentiation of C2C12 myoblasts. Betaine supplementation regulates fast to slow muscle fiber-type conversion and is associated with NFATc1/MyoD. Betaine supplementation enhances skeletal myogenesis in vivo. Betaine supplementation does not impair health of mice.

  16. Phosphate and acidosis act synergistically to depress peak power in rat muscle fibers.

    PubMed

    Nelson, Cassandra R; Debold, Edward P; Fitts, Robert H

    2014-11-15

    Skeletal muscle fatigue is characterized by the buildup of H(+) and inorganic phosphate (Pi), metabolites that are thought to cause fatigue by inhibiting muscle force, velocity, and power. While the individual effects of elevated H(+) or Pi have been well characterized, the effects of simultaneously elevating the ions, as occurs during fatigue in vivo, are still poorly understood. To address this, we exposed slow and fast rat skinned muscle fibers to fatiguing levels of H(+) (pH 6.2) and Pi (30 mM) and determined the effects on contractile properties. At 30°C, elevated Pi and low pH depressed maximal shortening velocity (Vmax) by 15% (4.23 to 3.58 fl/s) in slow and 31% (6.24 vs. 4.55 fl/s) in fast fibers, values similar to depressions from low pH alone. Maximal isometric force dropped by 36% in slow (148 to 94 kN/m(2)) and 46% in fast fibers (148 to 80 kN/m(2)), declines substantially larger than what either ion exerted individually. The strong effect on force combined with the significant effect on velocity caused peak power to decline by over 60% in both fiber types. Force-stiffness ratios significantly decreased with pH 6.2 + 30 mM Pi in both fiber types, suggesting these ions reduced force by decreasing the force per bridge and/or increasing the number of low-force bridges. The data indicate the collective effects of elevating H(+) and Pi on maximal isometric force and peak power are stronger than what either ion exerts individually and suggest the ions act synergistically to reduce muscle function during fatigue. Copyright © 2014 the American Physiological Society.

  17. Immunohistochemical localization of serotonin- and substance P-containing fibers around respiratory muscle motoneurons in the nucleus ambiguus of the cat.

    PubMed

    Holtman, J R

    1988-07-01

    Retrograde tracing with a fluorescent dye (Fast Blue) combined with immunohistochemistry was used to determine if the putative neurotransmitters, serotonin and substance P, are present around posterior cricoarytenoid muscle motoneurons. Fast Blue was injected into the posterior cricoarytenoid muscle of the larynx. Following a 14-21 day survival time to allow for transport of the dye, the animals were perfusion fixed and the brainstem was removed for analysis under the fluorescence microscope. Retrogradely labeled cell bodies containing Fast Blue were found within the nucleus ambiguus from 0.5 to 3.0 mm rostral to obex. These motoneurons ranged in size from 23 to 38 micron. The same tissue sections containing labeled posterior cricoarytenoid muscle motoneurons were then used to determine the distribution of serotonin and substance P around these motoneurons using the indirect immunofluorescence technique. A dense network of serotonin-containing immunoreactive fibers was found around posterior cricoarytenoid muscle motoneurons. The fibers contained varicosities which were in close proximity, actually appearing to surround these motoneurons. Substance P immunoreactive fibers and varicosities were also found around posterior cricoarytenoid muscle motoneurons. The density and pattern of distribution of the substance P immunoreactivity was similar to that of the serotonin immunoreactivity. These results suggest that these putative neurotransmitters may be involved in influencing the activity of posterior cricoarytenoid muscle motoneurons. Serotonin and substance P are also present around other respiratory motoneurons such as phrenic motoneurons. Therefore, these two neurotransmitters may have a more general role in influencing respiratory motor outflow.

  18. In vivo two-photon imaging of macrophage activities in skeletal muscle regeneration

    NASA Astrophysics Data System (ADS)

    Qin, Zhongya; Long, Yanyang; Sun, Qiqi; He, Sicong; Li, Xuesong; Chen, Congping; Wu, Zhenguo; Qu, Jianan Y.

    2018-02-01

    Macrophages are essential for the regeneration of skeletal muscle after injury. It has been demonstrated that depletion of macrophages results in delay of necrotic fiber phagocytosis and decreased size of regenerated myofibers. In this work, we developed a multi-modal two-photon microscope system for in vivo study of macrophage activities in the regenerative and fibrotic healing process of injured skeletal muscles. The system is capable to image the muscles based on the second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) signals simultaneously. The dynamic activities of macrophages and muscle satellite cells are recorded in different time windows post the muscle injury. Moreover, we found that infiltrating macrophages emitted strong autofluorescence in the injured skeletal muscle of mouse model, which has not been reported previously. The macrophage autofluorescence was characterized in both spectral and temporal domains. The information extracted from the autofluorescence signals may facilitate the understanding on the formation mechanisms and possible applications in biological research related to skeletal muscle regeneration.

  19. The Relationship between Muscle Fiber Type-Specific PGC-1α Content and Mitochondrial Content Varies between Rodent Models and Humans

    PubMed Central

    Gouspillou, Gilles; Sgarioto, Nicolas; Norris, Brandon; Barbat-Artigas, Sébastien; Aubertin-Leheudre, Mylène; Morais, Jose A.; Burelle, Yan; Taivassalo, Tanja; Hepple, Russell T.

    2014-01-01

    PGC-1α regulates critical processes in muscle physiology, including mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, PGC-1α was suggested as an important regulator of fiber type determination. However, whether a muscle fiber type-specific PGC-1α content exists, whether PGC-1α content relates to basal levels of mitochondrial content, and whether such relationships are preserved between humans and classically used rodent models are all questions that have been either poorly addressed or never investigated. To address these issues, we investigated the fiber type-specific content of PGC-1α and its relationship to basal mitochondrial content in mouse, rat and human muscles using in situ immunolabeling and histochemical methods on muscle serial cross-sections. Whereas type IIa fibers exhibited the highest PGC-1α in all three species, other fiber types displayed a hierarchy of type IIx>I>IIb in mouse, type I = IIx> IIb in rat, and type IIx>I in human. In terms of mitochondrial content, we observed a hierarchy of IIa>IIx>I>IIb in mouse, IIa >I>IIx> IIb in rat, and I>IIa> IIx in human skeletal muscle. We also found in rat skeletal muscle that type I fibers displayed the highest capillarization followed by type IIa >IIx>IIb. Finally, we found in human skeletal muscle that type I fibers display the highest lipid content, followed by type IIa>IIx. Altogether, our results reveal that (i) the fiber type-specific PGC-1α and mitochondrial contents were only matched in mouse, (ii) the patterns of PGC-1α and mitochondrial contents observed in mice and rats do not correspond to that seen in humans in several respects, and (iii) the classical phenotypes thought to be regulated by PGC-1α do not vary exclusively as a function of PGC-1α content in rat and human muscles. PMID:25121500

  20. Fiber type-specific muscle glycogen sparing due to carbohydrate intake before and during exercise.

    PubMed

    De Bock, K; Derave, W; Ramaekers, M; Richter, E A; Hespel, P

    2007-01-01

    The effect of carbohydrate intake before and during exercise on muscle glycogen content was investigated. According to a randomized crossover study design, eight young healthy volunteers (n = 8) participated in two experimental sessions with an interval of 3 wk. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% maximal oxygen uptake). On one occasion (CHO), they received carbohydrates before ( approximately 150 g) and during (1 g.kg body weight(-1).h(-1)) exercise. On the other occasion they exercised after an overnight fast (F). Fiber type-specific relative glycogen content was determined by periodic acid Schiff staining combined with immunofluorescence in needle biopsies from the vastus lateralis muscle before and immediately after exercise. Preexercise glycogen content was higher in type IIa fibers [9.1 +/- 1 x 10(-2) optical density (OD)/microm(2)] than in type I fibers (8.0 +/- 1 x 10(-2) OD/microm(2); P < 0.0001). Type IIa fiber glycogen content decreased during F from 9.6 +/- 1 x 10(-2) OD/microm(2) to 4.5 +/- 1 x 10(-2) OD/microm(2) (P = 0.001), but it did not significantly change during CHO (P = 0.29). Conversely, in type I fibers during CHO and F the exercise bout decreased glycogen content to the same degree. We conclude that the combination of carbohydrate intake both before and during moderate- to high-intensity endurance exercise results in glycogen sparing in type IIa muscle fibers.

  1. Effect of Hindlimb Unweighting on Single Soleus Fiber Maximal Shortening Velocity and ATPase Activity

    NASA Technical Reports Server (NTRS)

    McDonald, K. S.; Fitts, R. H.

    1993-01-01

    This study characterizes the time course of change in single soleus muscle fiber size and function elicited by hindlimb un weighting (HU) and analyzes the extent to which varying durations of HU altered maximal velocity of shortening (V(sub o)), myofibrillar adenosinetriphosphatase (ATPase), and relative content of slow and fast myosin in individual soleus fibers. After 1, 2, or 3 weeks of HU, soleus muscle bundles were prepared and stored in skinning solution at -20 C. Single fibers were isolated and mounted between a motor arm and a transducer, and fiber force, V(sub o), and ATPase activity were measured. Fiber myosin content was determined by one-dimensional sodium dodecyl sulfate- (SDS) polyacrylamide gel electrophoresis. After 1, 2, and 3 weeks of HU, soleus fibers exhibited a progressive reduction in fiber diameter (16, 22, and 42%, respectively) and peak force (42, 48, and 7%, respectively). Peak specific tension was significantly reduced after 1 week of HU (18%) and showed no further change in 2-3 weeks of HU. During 1 and 3 wk of HU, fiber V(sub o) and ATPase showed a significant increase. By 3 week, V(sub o) had increased from 1.32 +/- 0.04 to 2.94 +/- 0.17 fiber lengths/s and fiber ATPase from 291 +/- 16 to 1064 +/- 128 micro-M min(sub -1) mm(sub -3). The percent fibers expressing fast myosin heavy chain increased from 4% to 29% by 3 week of HU, and V(sub o) and ATPase activity within a fiber were highly correlated. However, a large population of fibers after 1, 2, and 3 weeks of HU showed increases in V(sub o) and ATPase but displayed the same myosin protein profile on SDS gels as control fibers. The mechanism eliciting increased fiber V(sub o) and ATPase activity was not obvious but may have been due to increases in fast myosin that went undetected on SDS gels and/or other factors unrelated to the myosin filament.

  2. Skeletal muscle adaptations to microgravity exposure in the mouse.

    PubMed

    Harrison, B C; Allen, D L; Girten, B; Stodieck, L S; Kostenuik, P J; Bateman, T A; Morony, S; Lacey, D; Leinwand, L A

    2003-12-01

    To investigate the effects of microgravity on murine skeletal muscle fiber size, muscle contractile protein, and enzymatic activity, female C57BL/6J mice, aged 64 days, were divided into animal enclosure module (AEM) ground control and spaceflight (SF) treatment groups. SF animals were flown on the space shuttle Endeavour (STS-108/UF-1) and subjected to approximately 11 days and 19 h of microgravity. Immunohistochemical analysis of muscle fiber cross-sectional area revealed that, in each of the muscles analyzed, mean muscle fiber cross-sectional area was significantly reduced (P < 0.0001) for all fiber types for SF vs. AEM control. In the soleus, immunohistochemical analysis of myosin heavy chain (MHC) isoform expression revealed a significant increase in the percentage of muscle fibers expressing MHC IIx and MHC IIb (P < 0.05). For the gastrocnemius and plantaris, no significant changes in MHC isoform expression were observed. For the muscles analyzed, no alterations in MHC I or MHC IIa protein expression were observed. Enzymatic analysis of the gastrocnemius revealed a significant decrease in citrate synthase activity in SF vs. AEM control.

  3. Maximal oxygen uptake is proportional to muscle fiber oxidative capacity, from chronic heart failure patients to professional cyclists.

    PubMed

    van der Zwaard, Stephan; de Ruiter, C Jo; Noordhof, Dionne A; Sterrenburg, Renske; Bloemers, Frank W; de Koning, Jos J; Jaspers, Richard T; van der Laarse, Willem J

    2016-09-01

    V̇o2 max during whole body exercise is presumably constrained by oxygen delivery to mitochondria rather than by mitochondria's ability to consume oxygen. Humans and animals have been reported to exploit only 60-80% of their mitochondrial oxidative capacity at maximal oxygen uptake (V̇o2 max). However, ex vivo quantification of mitochondrial overcapacity is complicated by isolation or permeabilization procedures. An alternative method for estimating mitochondrial oxidative capacity is via enzyme histochemical quantification of succinate dehydrogenase (SDH) activity. We determined to what extent V̇o2 max attained during cycling exercise differs from mitochondrial oxidative capacity predicted from SDH activity of vastus lateralis muscle in chronic heart failure patients, healthy controls, and cyclists. V̇o2 max was assessed in 20 healthy subjects and 28 cyclists, and SDH activity was determined from biopsy cryosections of vastus lateralis using quantitative histochemistry. Similar data from our laboratory of 14 chronic heart failure patients and 6 controls were included. Mitochondrial oxidative capacity was predicted from SDH activity using estimated skeletal muscle mass and the relationship between ex vivo fiber V̇o2 max and SDH activity of isolated single muscle fibers and myocardial trabecula under hyperoxic conditions. Mitochondrial oxidative capacity predicted from SDH activity was related (r(2) = 0.89, P < 0.001) to V̇o2 max measured during cycling in subjects with V̇o2 max ranging from 9.8 to 79.0 ml·kg(-1)·min(-1) V̇o2 max measured during cycling was on average 90 ± 14% of mitochondrial oxidative capacity. We conclude that human V̇o2 max is related to mitochondrial oxidative capacity predicted from skeletal muscle SDH activity. Mitochondrial oxidative capacity is likely marginally limited by oxygen supply to mitochondria. Copyright © 2016 the American Physiological Society.

  4. Sarcoplasmic reticulum Ca2+ permeation explored from the lumen side in mdx muscle fibers under voltage control

    PubMed Central

    Robin, Gaëlle; Berthier, Christine

    2012-01-01

    Under resting conditions, external Ca2+ is known to enter skeletal muscle cells, whereas Ca2+ stored in the sarcoplasmic reticulum (SR) leaks into the cytosol. The nature of the pathways involved in the sarcolemmal Ca2+ entry and in the SR Ca2+ leak is still a matter of debate, but several lines of evidence suggest that these Ca2+ fluxes are up-regulated in Duchenne muscular dystrophy. We investigated here SR calcium permeation at resting potential and in response to depolarization in voltage-controlled skeletal muscle fibers from control and mdx mice, the mouse model of Duchenne muscular dystrophy. Using the cytosolic Ca2+ dye Fura2, we first demonstrated that the rate of Ca2+ increase in response to cyclopiazonic acid (CPA)–induced inhibition of SR Ca2+-ATPases at resting potential was significantly higher in mdx fibers, which suggests an elevated SR Ca2+ leak. However, removal of external Ca2+ reduced the rate of CPA-induced Ca2+ increase in mdx and increased it in control fibers, which indicates an up-regulation of sarcolemmal Ca2+ influx in mdx fibers. Fibers were then loaded with the low-affinity Ca2+ dye Fluo5N-AM to measure intraluminal SR Ca2+ changes. Trains of action potentials, chloro-m-cresol, and depolarization pulses evoked transient Fluo5N fluorescence decreases, and recovery of voltage-induced Fluo5N fluorescence changes were inhibited by CPA, demonstrating that Fluo5N actually reports intraluminal SR Ca2+ changes. Voltage dependence and magnitude of depolarization-induced SR Ca2+ depletion were found to be unchanged in mdx fibers, but the rate of the recovery phase that followed depletion was found to be faster, indicating a higher SR Ca2+ reuptake activity in mdx fibers. Overall, CPA-induced SR Ca2+ leak at −80 mV was found to be significantly higher in mdx fibers and was potentiated by removal of external Ca2+ in control fibers. The elevated passive SR Ca2+ leak may contribute to alteration of Ca2+ homeostasis in mdx muscle. PMID:22371362

  5. Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey.

    PubMed

    Fitts, R H; Desplanches, D; Romatowski, J G; Widrick, J J

    2000-11-01

    The purpose of this investigation was to understand how 14 days of weightlessness alters the cellular properties of individual slow- and fast-twitch muscle fibers in the rhesus monkey. The diameter of the soleus (Sol) type I, medial gastrocnemius (MG) type I, and MG type II fibers from the vivarium controls averaged 60 +/- 1, 46 +/- 2, and 59 +/- 2 microm, respectively. Both a control 1-G capsule sit (CS) and spaceflight (SF) significantly reduced the Sol type I fiber diameter (20 and 13%, respectively) and peak force, with the latter declining from 0.48 +/- 0.01 to 0.31 +/- 0.02 (CS group) and 0.32 +/- 0.01 mN (SF group). When the peak force was expressed as kiloNewtons per square meter (kN/m(2)), only the SF group showed a significant decline. This group also showed a significant 15% drop in peak fiber stiffness that suggests that fewer cross bridges were contracting in parallel. In the MG, SF but not CS depressed the type I fiber diameter and force. Additionally, SF significantly depressed absolute (mN) and relative (kN/m(2)) force in the fast-twitch MG fibers by 30% and 28%, respectively. The Ca(2+) sensitivity of the type I fiber (Sol and MG) was significantly reduced by growth but unaltered by SF. Flight had no significant effect on the mean maximal fiber shortening velocity in any fiber type or muscle. The post-SF Sol type I fibers showed a reduced peak power and, at peak power, an elevated velocity and decreased force. In conclusion, CS and SF caused atrophy and a reduced force and power in the Sol type I fiber. However, only SF elicited atrophy and reduced force (mN) in the MG type I fiber and a decline in relative force (kN/m(2)) in the Sol type I and MG type II fibers.

  6. Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Desplanches, D.; Romatowski, J. G.; Widrick, J. J.

    2000-01-01

    The purpose of this investigation was to understand how 14 days of weightlessness alters the cellular properties of individual slow- and fast-twitch muscle fibers in the rhesus monkey. The diameter of the soleus (Sol) type I, medial gastrocnemius (MG) type I, and MG type II fibers from the vivarium controls averaged 60 +/- 1, 46 +/- 2, and 59 +/- 2 microm, respectively. Both a control 1-G capsule sit (CS) and spaceflight (SF) significantly reduced the Sol type I fiber diameter (20 and 13%, respectively) and peak force, with the latter declining from 0.48 +/- 0.01 to 0.31 +/- 0.02 (CS group) and 0.32 +/- 0.01 mN (SF group). When the peak force was expressed as kiloNewtons per square meter (kN/m(2)), only the SF group showed a significant decline. This group also showed a significant 15% drop in peak fiber stiffness that suggests that fewer cross bridges were contracting in parallel. In the MG, SF but not CS depressed the type I fiber diameter and force. Additionally, SF significantly depressed absolute (mN) and relative (kN/m(2)) force in the fast-twitch MG fibers by 30% and 28%, respectively. The Ca(2+) sensitivity of the type I fiber (Sol and MG) was significantly reduced by growth but unaltered by SF. Flight had no significant effect on the mean maximal fiber shortening velocity in any fiber type or muscle. The post-SF Sol type I fibers showed a reduced peak power and, at peak power, an elevated velocity and decreased force. In conclusion, CS and SF caused atrophy and a reduced force and power in the Sol type I fiber. However, only SF elicited atrophy and reduced force (mN) in the MG type I fiber and a decline in relative force (kN/m(2)) in the Sol type I and MG type II fibers.

  7. The Tropomyosin Binding Region of Cardiac Troponin T Modulates Crossbridge Recruitment Dynamics in Rat Cardiac Muscle Fibers

    PubMed Central

    Gollapudi, Sampath K.; Gallon, Clare E.; Chandra, Murali

    2013-01-01

    The cardiac muscle comprises dynamically interacting components that use allosteric/cooperative mechanisms to yield unique heart-specific properties. An essential protein in this allosteric/cooperative mechanism is cardiac muscle troponin T (cTnT), the central region (CR) and the T2 region of which differ significantly from those of fast skeletal muscle troponin T (fsTnT). To understand the biological significance of such sequence heterogeneity, we replaced the T1 or T2 domain of rat cTnT (RcT1 or RcT2) with its counterpart from rat fsTnT (RfsT1or RfsT2) to generate RfsT1-RcT2 and RcT1-RfsT2 recombinant proteins. In addition to contractile function measurements, dynamic features of RfsT1-RcT2 and RcT1-RfsT2 reconstituted rat cardiac muscle fibers were captured by fitting the recruitment-distortion model to force response of small amplitude (0.5%) muscle length changes. RfsT1-RcT2 fibers showed a ~40% decrease in tension and ~44% decrease in ATPase activity, but RcT1-RfsT2 fibers were unaffected. The magnitude of length-mediated increase in crossbridge recruitment (E0) decreased by ~33% and the speed of crossbridge recruitment (b) increased by ~100% in RfsT1-RcT2 fibers. Our data suggest the following: (1) the CR of cTnT modulates crossbridge recruitment dynamics; (2) the N-terminal end region of cTnT has a synergistic effect on the ability of CR to modulate crossbridge recruitment dynamics; (3) the T2 region is important for tuning the Ca2+ regulation of cardiac thin filaments. The combined effects of CR-Tm interactions and the modulating effect of the N-terminal end of cTnT on CR-Tm interactions may lead to the emergence of a unique property that tunes contractile dynamics to heart rates. PMID:23357173

  8. Hypogravity-induced atrophy of rat soleus and extensor digitorum longus muscles

    NASA Technical Reports Server (NTRS)

    Riley, D. A.; Ellis, S.; Slocum, G. R.; Satyanarayana, T.; Bain, J. L.; Sedlak, F. R.

    1987-01-01

    Prolonged exposure of humans to hypogravity causes weakening of their skeletal muscles. This problem was studied in rats exposed to hypogravity for 7 days aboard Spacelab 3. Hindlimb muscles were harvested 12-16 hours postflight for histochemical, biochemical, and ultrastructural analyses. The majority of the soleus and extensor digitorum longus fibers exhibited simple cell shrinkage. However, approximately 1% of the fibers in flight soleus muscles appeared necrotic. Flight muscle fibers showed increased glycogen, lower subsarcolemmal staining for mitochondrial enzymes, and fewer subsarcolemmal mitochondria. During atrophy, myofibrils were eroded by multiple focal losses of myofilaments; lysosomal autophagy was not evident. Tripeptidylaminopeptidase and calcium-activated protease activities of flight soleus fibers were significantly increased, implying a role in myofibril breakdown. Simple fiber atrophy appears to account for muscle weakening during spaceflight, but fiber necrosis is also a contributing factor.

  9. Mechanical Properties of Respiratory Muscles

    PubMed Central

    Sieck, Gary C.; Ferreira, Leonardo F.; Reid, Michael B.; Mantilla, Carlos B.

    2014-01-01

    Striated respiratory muscles are necessary for lung ventilation and to maintain the patency of the upper airway. The basic structural and functional properties of respiratory muscles are similar to those of other striated muscles (both skeletal and cardiac). The sarcomere is the fundamental organizational unit of striated muscles and sarcomeric proteins underlie the passive and active mechanical properties of muscle fibers. In this respect, the functional categorization of different fiber types provides a conceptual framework to understand the physiological properties of respiratory muscles. Within the sarcomere, the interaction between the thick and thin filaments at the level of cross-bridges provides the elementary unit of force generation and contraction. Key to an understanding of the unique functional differences across muscle fiber types are differences in cross-bridge recruitment and cycling that relate to the expression of different myosin heavy chain isoforms in the thick filament. The active mechanical properties of muscle fibers are characterized by the relationship between myoplasmic Ca2+ and cross-bridge recruitment, force generation and sarcomere length (also cross-bridge recruitment), external load and shortening velocity (cross-bridge cycling rate), and cross-bridge cycling rate and ATP consumption. Passive mechanical properties are also important reflecting viscoelastic elements within sarcomeres as well as the extracellular matrix. Conditions that affect respiratory muscle performance may have a range of underlying pathophysiological causes, but their manifestations will depend on their impact on these basic elemental structures. PMID:24265238

  10. Nicorandil improves post-fatigue tension in slow skeletal muscle fibers by modulating glutathione redox state.

    PubMed

    Sánchez-Duarte, E; Trujillo, X; Cortés-Rojo, C; Saavedra-Molina, A; Camargo, G; Hernández, L; Huerta, M; Montoya-Pérez, R

    2017-04-01

    Fatigue is a phenomenon in which force reduction has been linked to impairment of several biochemical processes. In skeletal muscle, the ATP-sensitive potassium channels (K ATP ) are actively involved in myoprotection against metabolic stress. They are present in sarcolemma and mitochondria (mitoK ATP channels). K + channel openers like nicorandil has been recognized for their ability to protect skeletal muscle from ischemia-reperfusion injury, however, the effects of nicorandil on fatigue in slow skeletal muscle fibers has not been explored, being the aim of this study. Nicorandil (10 μM), improved the muscle function reversing fatigue as increased post-fatigue tension in the peak and total tension significantly with respect to the fatigued condition. However, this beneficial effect was prevented by the mitoK ATP channel blocker 5-hydroxydecanoate (5-HD, 500 μM) and by the free radical scavenger N-2-mercaptopropionyl glycine (MPG, 1 mM), but not by the nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM). Nicorandil also decreased lipid peroxidation and maintained both reduced glutathione (GSH) levels and an elevated GSH/GSSG ratio, whereas total glutathione (TGSH) remained unaltered during post-fatigue tension. In addition, NO production, measured through nitrite concentrations was significantly increased with nicorandil during post-fatigue tension; this increase remained unaltered in the presence of nicorandil plus L-NAME, nonetheless, this effect was reversed with nicorandil plus MPG. Hence, these results suggest that nicorandil improves the muscle function reversing fatigue in slow skeletal muscle fibers of chicken through its effects not only as a mitoK ATP channel opener but also as NO donor and as an antioxidant.

  11. Optical characteristics of modified fiber tips in single fiber, laser Doppler flowmetry

    NASA Astrophysics Data System (ADS)

    Oberg, P. Ake; Cai, Hongming; Rohman, Hakan; Larsson, Sven-Erik

    1994-02-01

    Percutaneous laser Doppler flowmetry (LDF) and bipolar surface electromyography (EMG) were used simultaneously for measurement of skeletal muscle (trapezius) perfusion in relation to static load and fatigue. On-line computer (386 SX) processing of the LDF- and EMG- signals made possible interpretation of the relationship between the perfusion and the activity of the muscle. The single fiber laser Doppler technique was used in order to minimize the trauma. A ray-tracing program was developed in the C language by which the optical properties of the fiber and fiber ends could be simulated. Isoirradiance graphs were calculated for three fiber end types and the radiance characteristics were measured for each fiber end. The three types of fiber-tips were evaluated and compared in flow model measurements.

  12. Role of selected polymorphisms in determining muscle fiber composition in Japanese men and women.

    PubMed

    Kumagai, Hiroshi; Tobina, Takuro; Ichinoseki-Sekine, Noriko; Kakigi, Ryo; Tsuzuki, Takamasa; Zempo, Hirofumi; Shiose, Keisuke; Yoshimura, Eiichi; Kumahara, Hideaki; Ayabe, Makoto; Higaki, Yasuki; Yamada, Ryo; Kobayashi, Hiroyuki; Kiyonaga, Akira; Naito, Hisashi; Tanaka, Hiroaki; Fuku, Noriyuki

    2018-05-01

    Genetic polymorphisms and sex differences are suggested to affect muscle fiber composition; however, no study has investigated the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences. Therefore, the present study examined the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences in the Japanese population. The present study included 211 healthy Japanese individuals (102 men and 109 women). Muscle biopsies were obtained from the vastus lateralis to determine the proportion of myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa, and MHC-IIx). Moreover, we analyzed polymorphisms in α-actinin-3 gene ( ACTN3; rs1815739 ), angiotensin-converting enzyme gene ( ACE; rs4341 ), hypoxia-inducible factor 1 α gene ( rs11549465 ), vascular endothelial growth factor receptor 2 gene ( rs1870377 ), and angiotensin II receptor, type 2 gene ( rs11091046 ), by TaqMan single-nucleotide polymorphism genotyping assays. The proportion of MHC-I was 9.8% lower in men than in women, whereas the proportion of MHC-IIa and MHC-IIx was higher in men than in women (5.0 and 4.6%, respectively). Men with the ACTN3 RR + RX genotype had a 4.8% higher proportion of MHC-IIx than those with the ACTN3 XX genotype. Moreover, men with the ACE ID + DD genotype had a 4.7% higher proportion of MHC-I than those with the ACE II genotype. Furthermore, a combined genotype of ACTN3 R577X and ACE insertion/deletion (I/D) was significantly correlated with the proportion of MHC-I ( r = -0.23) and MHC-IIx ( r = 0.27) in men. In contrast, no significant correlation was observed between the examined polymorphisms and muscle fiber composition in women. These results suggest that the ACTN3 R577X and ACE I/D polymorphisms independently affect the proportion of human skeletal muscle fibers MHC-I and MHC-IIx in men but not in women. NEW & NOTEWORTHY In men, the RR + RX genotype of the α-actinin-3 gene ( ACTN3) R577X polymorphism was

  13. Orientation of the N-terminal lobe of the myosin regulatory light chain in skeletal muscle fibers.

    PubMed

    Romano, Daniela; Brandmeier, Birgit D; Sun, Yin-Biao; Trentham, David R; Irving, Malcolm

    2012-03-21

    The orientation of the N-terminal lobe of the myosin regulatory light chain (RLC) in demembranated fibers of rabbit psoas muscle was determined by polarized fluorescence. The native RLC was replaced by a smooth muscle RLC with a bifunctional rhodamine probe attached to its A, B, C, or D helix. Fiber fluorescence data were interpreted using the crystal structure of the head domain of chicken skeletal myosin in the nucleotide-free state. The peak angle between the lever axis of the myosin head and the fiber or actin filament axis was 100-110° in relaxation, isometric contraction, and rigor. In each state the hook helix was at an angle of ∼40° to the lever/filament plane. The in situ orientation of the RLC D and E helices, and by implication of its N- and C-lobes, was similar in smooth and skeletal RLC isoforms. The angle between these two RLC lobes in rigor fibers was different from that in the crystal structure. These results extend previous crystallographic evidence for bending between the two lobes of the RLC to actin-attached myosin heads in muscle fibers, and suggest that such bending may have functional significance in contraction and regulation of vertebrate striated muscle. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Heat stress increases myonuclear number and fiber size via satellite cell activation in rat regenerating soleus fibers.

    PubMed

    Oishi, Yasuharu; Hayashida, Mari; Tsukiashi, Shinsuke; Taniguchi, Kohachi; Kami, Katsuya; Roy, Roland R; Ohira, Yoshinobu

    2009-11-01

    To investigate the effects of heat stress (hyperthermia) on muscle degeneration-regeneration, the soleus muscles of adult male Wistar rats were injected bilaterally with a single injection of bupivacaine. The rats were assigned to a sedentary control (Con), heat stress (Heat), bupivacaine-injected (BPVC), or bupivacaine-injected plus heat stress (BPVC+Heat) group. Heat stress was induced in the Heat and BPVC+Heat groups by immersion of the lower half of the body into water maintained at 42 +/- 1 degrees C for 30 min 48 h after the injection of bupivacaine and every other day during the following 1 or 2 wk. The soleus muscles in all groups were excised 24 h after the final bout of heat stress. Mean muscle weight, fiber cross-sectional area, myonuclear number, and heat shock protein 72 (Hsp72) and calcineurin protein levels were lower in the BPVC than in the Con or Heat groups at both time points. In contrast, several of these parameters in the BPVC+Heat group were not different or higher than in the Con or Heat groups at the 1- and/or 2-wk time points. The number of total and activated satellite cells, estimated by analyses of Pax7-negative, M-cadherin-negative, and MyoD-positive nuclei, was greater in BPVC+Heat than in all other groups. Combined, the results indicate that heat stress-related activation of satellite cells and upregulation of Hsp72 and calcineurin expression played important roles in the regeneration of the soleus fibers after bupivacaine injection.

  15. Numerous eosinophilic globules (skeinoid fibers) in a duodenal stromal tumor: an exceptional case showing smooth muscle differentiation.

    PubMed

    Matsukuma, S; Doi, M; Suzuki, M; Ikegawa, K; Sato, K; Kuwabara, N

    1997-11-01

    A unique case of duodenal stromal tumor in a 51-year-old man is reported. The tumor histologically showed spindle cell proliferation and numerous eosinophilic globules. Most globules were composed of tangled 45 nm thick fibrils, which were ultrastructurally identical to 'skeinoid fibers'. The presence of glycogen granules in the tumor cells and the immunoreactivity for alpha-smooth muscle actin suggested smooth muscle differentiation. Focal ultrastructural findings also supported the smooth muscle nature of this tumor. There were no immunohistochemical and ultrastructural features indicating neural differentiation. In previous studies, the presence of such 'skeinoid fibers' was suggested to be a histological marker for neural differentiation in gastrointestinal stromal tumor. However, the findings in the present case suggest that numerous 'skeinoid fibers' can be identified in duodenal stromal tumor with smooth muscle differentiation, although this condition may be rare.

  16. Impact of weightlessness on muscle function

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Slentz, M.

    1995-01-01

    The most studied skeletal muscles which depend on gravity, "antigravity" muscles, are located in the posterior portion of the legs. Antigravity muscles are characterized generally by a different fiber type composition than those which are considered nonpostural. The gravity-dependent function of the antigravity muscles makes them particularly sensitive to weightlessness (unweighting) resulting in a substantial loss of muscle protein, with a relatively greater loss of myofibrillar (structural) proteins. Accordingly alpha-actin mRNA decreases in muscle of rats exposed to microgravity. In the legs, the soleus seems particularly responsive to the lack of weight-bearing associated with space flight. The loss of muscle protein leads to a decreased cross-sectional area of muscle fibers, particularly of the slow-twitch, oxidative (SO) ones compared to fast-twitch glycolytic (FG) or oxidative-glycolytic (FOG) fibers. In some muscles, a shift in fiber composition from SO to FOG has been reported in the adaptation to spaceflight. Changes in muscle composition with spaceflight have been associated with decreased maximal isometric tension (Po) and increased maximal shortening velocity. In terms of fuel metabolism, results varied depending on the pathway considered. Glucose uptake, in the presence of insulin, and activities of glycolytic enzymes are increased by space flight. In contrast, oxidation of fatty acids may be diminished. Oxidation of pyruvate, activity of the citric acid cycle, and ketone metabolism in muscle seem to be unaffected by microgravity.

  17. Mathematical modeling and fluorescence imaging to study the Ca2+ turnover in skinned muscle fibers.

    PubMed Central

    Uttenweiler, D; Weber, C; Fink, R H

    1998-01-01

    A mathematical model was developed for the simulation of the spatial and temporal time course of Ca2+ ion movement in caffeine-induced calcium transients of chemically skinned muscle fiber preparations. Our model assumes cylindrical symmetry and quantifies the radial profile of Ca2+ ion concentration by solving the diffusion equations for Ca2+ ions and various mobile buffers, and the rate equations for Ca2+ buffering (mobile and immobile buffers) and for the release and reuptake of Ca2+ ions by the sarcoplasmic reticulum (SR), with a finite-difference algorithm. The results of the model are compared with caffeine-induced spatial Ca2+ transients obtained from saponin skinned murine fast-twitch fibers by fluorescence photometry and imaging measurements using the ratiometric dye Fura-2. The combination of mathematical modeling and digital image analysis provides a tool for the quantitative description of the total Ca2+ turnover and the different contributions of all interacting processes to the overall Ca2+ transient in skinned muscle fibers. It should thereby strongly improve the usage of skinned fibers as quantitative assay systems for many parameters of the SR and the contractile apparatus helping also to bridge the gap to the intact muscle fiber. PMID:9545029

  18. Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading

    NASA Technical Reports Server (NTRS)

    Carlson, C. J.; Booth, F. W.; Gordon, S. E.

    1999-01-01

    Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S. -J. Lee. Nature 387: 83-90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation (r = 0.725, P < 0. 0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

  19. Two fast-type fibers in claw closer and abdominal deep muscles of the Australian freshwater crustacean, Cherax destructor, differ in Ca2+ sensitivity and troponin-I isoforms.

    PubMed

    Koenders, Annette; Lamey, Tina M; Medler, Scott; West, Jan M; Mykles, Donald L

    2004-07-01

    One type of fast fiber and two types of slow (slow-twitch, S1 and slow-tonic, S2) fibers are found in decapod crustacean skeletal muscles that differ in contractile properties and myofibrillar protein isoform compositions. In this study the structural characteristics, protein isoform compositions, and Ca2+-activation properties of fast fibers in the claw closer (F1) and abdominal deep flexor (F2) muscles of Cherax destructor were analyzed. For comparison, myofibrillar protein isoform compositions of slow (long-sarcomere) fibers from claw and abdomen were also determined; our results indicate that the slow fibers in the claw closer were the slow-twitch (S1) type and those in the abdominal superficial flexor were primarily slow-tonic (S2) type. F1 fibers had shorter resting sarcomere lengths (2.93 microm in unstretched fibers and 3.06 microm in stretched fibers) and smaller fiber diameter (256 microm) than F2 fibers (sarcomere lengths 3.48 microm in unstretched and 3.46 microm in stretched; 747 microm diameter). Moreover, F1 fibers showed a narrower range in sarcomere lengths than F2 fibers (2.81 to 3.28 microm vs. 2.47 to 4.05 micro m in unstretched fibers). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting showed that the fast fibers from claw and abdomen differed in troponin-I composition; F1 fibers expressed two isoforms of troponin-I (TnI1 and TnI2) in approximately equal amounts, whereas F2 fibers expressed primarily TnI3 and lower levels of TnI1. F1 fibers were more sensitive to Ca2+, as shown by higher pCa values at threshold activation (pCa(10)=6.50+/-0.07) and at 50% maximum force (pCa(50)=6.43+/-0.07) than F2 fibers (pCa(10)=6.12+/-0.04 and pCa(50)=5.88+/-0.03, respectively). F1 fibers also had a greater degree of co-operativity in Ca2+ activation, as shown by a higher maximum slope of the force-pCa curve (n(Ca)=12.98+/-2.27 vs. 4.34+/-0.64). These data indicate that there is a greater fast fiber-type diversity in crustacean

  20. Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding

    PubMed Central

    De Andrade, Paula B. M.; Neff, Laurence A.; Strosova, Miriam K.; Arsenijevic, Denis; Patthey-Vuadens, Ophélie; Scapozza, Leonardo; Montani, Jean-Pierre; Ruegg, Urs T.; Dulloo, Abdul G.; Dorchies, Olivier M.

    2015-01-01

    Weight regain after caloric restriction results in accelerated fat storage in adipose tissue. This catch-up fat phenomenon is postulated to result partly from suppressed skeletal muscle thermogenesis, but the underlying mechanisms are elusive. We investigated whether the reduced rate of skeletal muscle contraction-relaxation cycle that occurs after caloric restriction persists during weight recovery and could contribute to catch-up fat. Using a rat model of semistarvation-refeeding, in which fat recovery is driven by suppressed thermogenesis, we show that contraction and relaxation of leg muscles are slower after both semistarvation and refeeding. These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers. These semistarvation-induced changes persisted during recovery and correlated with impaired expression of transcription factors involved in slow-twitch muscle development. We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility. These energy-sparing effects persist during weight recovery and contribute to catch-up fat. PMID:26441673

  1. Muscle ultrastructural changes from exhaustive exercise performed after prolonged restricted activity and retraining in dogs

    NASA Technical Reports Server (NTRS)

    Nazar, K.; Greenleaf, J. E.; Philpott, D.; Pohoska, E.; Olszewska, K.; Kaciuba-Uscilko, H.

    1991-01-01

    The effect of exhaustive treadmill exercise on ultrastructural changes in the quadriceps femoris muscle was studied in 7 normal, healthy dogs, before and after restricted activity (RA), and following a subsequent 2 month treadmill exercise retraining period for the 5 mo group. Mean time to exhaustion in the 2 mo group decreased from 177 + or - 22 min before to 90 + or - 32 min after RA. Retraining increased tolerance to 219 + or - 73 min; 24 pct. above the before RA and 143 pct. above the after RA time. After RA exhaustion time in the 5 mo group was 25 and 45 min. Before RA, pre-exercise muscle structure was normal and post exercise there was only slight swelling of mitochondria. After RA, pre-exercise, numerous glycogen granules and lipid droplets appeared in the muscle fibers, mitochondria were smaller, and sarcoplasmic reticulum channels widened; post exercise these changes were accentuated and some areas were devoid of glycogen, and there was fiber degradation. After 5 mo RA pre-exercise there were more pronounced changes; mitochondria were very small and dense, there were many lipid droplets, myofibrils were often separated, and the fibers appeared edematous and degenerating; post exercise the sarcoplasmic reticulum was swollen, no glycogen was present, and there was marked swelling and deformation of mitochondria. After retraining, both pre-exercise and post exercise there was still evidence of fiber degeneration. Thus, susceptibility of active skeletal muscle structures and subcellular elements, e.g., mitochondria, to the action of damaging factors occurring during exhaustive exercise is enhanced considerably by prolonged disuse.

  2. History dependence of human muscle-fiber conduction velocity during voluntary isometric contractions.

    PubMed

    McGill, Kevin C; Lateva, Zoia C

    2011-09-01

    The conduction velocity (CV) of a muscle fiber is affected by the fiber's discharge history going back ∼1 s. We investigated this dependence by measuring CV fluctuations during voluntary isometric contractions of the human brachioradialis muscle. We recorded electromyogram (EMG) signals simultaneously from multiple intramuscular electrodes, identified potentials belonging to the same motor unit using EMG decomposition, and estimated the CV of each discharge from the interpotential interval. In 12 of 14 subjects, CV increased by ∼10% during the first second after recruitment and then fluctuated by about ±2% in a way that mirrored the fluctuations in the instantaneous firing rate. The CV profile could be precisely described in terms of the discharge history by a simple mathematical model. In the other two subjects, and one subject retested after cooling the arm, the CV fluctuations were inversely correlated with instantaneous firing rate. In all subjects, CV was additionally affected by very short interdischarge intervals (<25 ms): it was increased in doublets at recruitment, but decreased in doublets during continuous firing and after short interdischarge intervals in doubly innervated fibers. CV also exhibited a slow trend of about -0.05%/s that did not depend on the immediate discharge history. We suggest that measurements of CV fluctuations during voluntary contractions, or during stimulation protocols that involve longer and more complex stimulation patterns than are currently being used, may provide a sensitive approach for estimating the dynamic characteristics of ion channels in the human muscle-fiber membrane.

  3. History dependence of human muscle-fiber conduction velocity during voluntary isometric contractions

    PubMed Central

    Lateva, Zoia C.

    2011-01-01

    The conduction velocity (CV) of a muscle fiber is affected by the fiber's discharge history going back ∼1 s. We investigated this dependence by measuring CV fluctuations during voluntary isometric contractions of the human brachioradialis muscle. We recorded electromyogram (EMG) signals simultaneously from multiple intramuscular electrodes, identified potentials belonging to the same motor unit using EMG decomposition, and estimated the CV of each discharge from the interpotential interval. In 12 of 14 subjects, CV increased by ∼10% during the first second after recruitment and then fluctuated by about ±2% in a way that mirrored the fluctuations in the instantaneous firing rate. The CV profile could be precisely described in terms of the discharge history by a simple mathematical model. In the other two subjects, and one subject retested after cooling the arm, the CV fluctuations were inversely correlated with instantaneous firing rate. In all subjects, CV was additionally affected by very short interdischarge intervals (<25 ms): it was increased in doublets at recruitment, but decreased in doublets during continuous firing and after short interdischarge intervals in doubly innervated fibers. CV also exhibited a slow trend of about −0.05%/s that did not depend on the immediate discharge history. We suggest that measurements of CV fluctuations during voluntary contractions, or during stimulation protocols that involve longer and more complex stimulation patterns than are currently being used, may provide a sensitive approach for estimating the dynamic characteristics of ion channels in the human muscle-fiber membrane. PMID:21565985

  4. Zebrafish embryos exposed to alcohol undergo abnormal development of motor neurons and muscle fibers.

    PubMed

    Sylvain, Nicole J; Brewster, Daniel L; Ali, Declan W

    2010-01-01

    Children exposed to alcohol in utero have significantly delayed gross and fine motor skills, as well as deficiencies in reflex development. The reasons that underlie the motor deficits caused by ethanol (EtOH) exposure remain to be fully elucidated. The present study was undertaken to investigate the effects of embryonic alcohol exposure (1.5%, 2% and 2.5% EtOH) on motor neuron and muscle fiber morphology in 3 days post fertilization (dpf) larval zebrafish. EtOH treated fish exhibited morphological deformities and fewer bouts of swimming in response to touch, compared with untreated fish. Immunolabelling with anti-acetylated tubulin indicated that fish exposed to 2.5% EtOH had significantly higher rates of motor neuron axon defects. Immunolabelling of primary and secondary motor neurons, using znp-1 and zn-8, revealed that fish exposed to 2% and 2.5% EtOH exhibited significantly higher rates of primary and secondary motor neuron axon defects compared to controls. Examination of red and white muscle fibers revealed that fish exposed to EtOH had significantly smaller fibers compared with controls. These findings indicate that motor neuron and muscle fiber morphology is affected by early alcohol exposure in zebrafish embryos, and that this may be related to deficits in locomotion. Copyright 2010 Elsevier Inc. All rights reserved.

  5. [Desmin content and transversal stiffness of the left ventricle mouse cardiomyocytes and skeletal muscle fibers after a 30-day space flight on board "BION-M1" biosatellite].

    PubMed

    Ogneva, I V; Maximova, M V; Larina, I M

    2014-01-01

    The aim of this study was to determine the transversal stiffness of the cortical cytoskeleton and the cytoskeletal protein desmin content in the left ventricle cardiomyocytes, fibers of the mouse soleus and tibialis anterior muscle after a 30-day space flight on board the "BION-M1" biosatellite (Russia, 2013). The dissection was made after 13-16.5 h after landing. The transversal stiffness was measured in relaxed and calcium activated state by, atomic force microscopy. The desmin content was estimated by western blotting, and the expression level of desmin-coding gene was detected using real-time PCR. The results indicate that, the transversal stiffness of the left ventricle cardiomyocytes and fibers of the soleus muscle in relaxed and activated states did not differ from the control. The transversal stiffness of the tibialis muscle fibers in relaxed and activated state was increased in the mice group after space flight. At the same time, in all types of studied tissues the desmin content and the expression level of desmin-coding gene did not differ from the control level.

  6. Insulin-induced redistribution of GLUT4 glucose carriers in the muscle fiber. In search of GLUT4 trafficking pathways.

    PubMed

    Zorzano, A; Muñoz, P; Camps, M; Mora, C; Testar, X; Palacín, M

    1996-01-01

    Insulin rapidly stimulates glucose transport in muscle fiber. This process controls the utilization of glucose in skeletal muscle, and it is deficient in various insulin-resistant states, such as non-insulin-dependent diabetes mellitus. The effect of insulin on muscle glucose transport is mainly due to the recruitment of GLUT4 glucose carriers to the cell surface of the muscle fiber. There is increasing evidence that the recruitment of GLUT4 carriers triggered by insulin affects selective domains of sarcolemma and transverse tubules. In contrast, GLUT1 is located mainly in sarcolemma and is absent in transverse tubules, and insulin does not alter its cellular distribution in muscle fiber. The differential distribution of GLUT1 and GLUT4 in the cell surface raises new questions regarding the precise endocytic and exocytic pathways that are functional in the muscle fiber. The current view of insulin-induced GLUT4 translocation is based mainly on studies performed in adipocytes. These studies have proposed the existence of intracellular compartments of GLUT4 that respond to insulin in a highly homogeneous manner. However, studies performed in skeletal muscle have identified insulin-sensitive as well as insulin-insensitive intracellular GLUT4-containing membranes. These data open a new perspective on the dynamics of intracellular GLUT4 compartments in insulin-sensitive cells.

  7. Voluntary physical activity protects from susceptibility to skeletal muscle contraction-induced injury but worsens heart function in mdx mice.

    PubMed

    Hourdé, Christophe; Joanne, Pierre; Medja, Fadia; Mougenot, Nathalie; Jacquet, Adeline; Mouisel, Etienne; Pannerec, Alice; Hatem, Stéphane; Butler-Browne, Gillian; Agbulut, Onnik; Ferry, Arnaud

    2013-05-01

    It is well known that inactivity/activity influences skeletal muscle physiological characteristics. However, the effects of inactivity/activity on muscle weakness and increased susceptibility to muscle contraction-induced injury have not been extensively studied in mdx mice, a murine model of Duchenne muscular dystrophy with dystrophin deficiency. In the present study, we demonstrate that inactivity (ie, leg immobilization) worsened the muscle weakness and the susceptibility to contraction-induced injury in mdx mice. Inactivity also mimicked these two dystrophic features in wild-type mice. In contrast, we demonstrate that these parameters can be improved by activity (ie, voluntary wheel running) in mdx mice. Biochemical analyses indicate that the changes induced by inactivity/activity were not related to fiber-type transition but were associated with altered expression of different genes involved in fiber growth (GDF8), structure (Actg1), and calcium homeostasis (Stim1 and Jph1). However, activity reduced left ventricular function (ie, ejection and shortening fractions) in mdx, but not C57, mice. Altogether, our study suggests that muscle weakness and susceptibility to contraction-induced injury in dystrophic muscle could be attributable, at least in part, to inactivity. It also suggests that activity exerts a beneficial effect on dystrophic skeletal muscle but not on the heart. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Differential sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy.

    PubMed

    de Theije, C C; Langen, R C J; Lamers, W H; Gosker, H R; Schols, A M W J; Köhler, S E

    2015-01-15

    Hypoxia as a consequence of acute and chronic respiratory disease has been associated with muscle atrophy. This study investigated the sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy. Male mice were exposed to 8% normobaric oxygen for up to 21 days. Oxidative soleus and glycolytic extensor digitorum longus (EDL) muscles were isolated, weighed, and assayed for expression profiles of the ubiquitin-proteasome system (UPS), the autophagy-lysosome pathway (ALP), and glucocorticoid receptor (GR) and hypoxia-inducible factor-1α (HIF1α) signaling. Fiber-type composition and the capillary network were investigated. Hypoxia-induced muscle atrophy was more prominent in the EDL than the soleus muscle. Although increased expression of HIF1α target genes showed that both muscle types sensed hypoxia, their adaptive responses differed. Atrophy consistently involved a hypoxia-specific effect (i.e., not attributable to a hypoxia-mediated reduction of food intake) in the EDL only. Hypoxia-specific activation of the UPS and ALP and increased expression of the glucocorticoid receptor (Gr) and its target genes were also mainly observed in the EDL. In the soleus, stimulation of gene expression of those pathways could be mimicked to a large extent by food restriction alone. Hypoxia increased the number of capillary contacts per fiber cross-sectional area in both muscles. In the EDL, this was due to type II fiber atrophy, whereas in the soleus the absolute number of capillary contacts increased. These responses represent two distinct modes to improve oxygen supply to muscle fibers, but may aggravate muscle atrophy in chronic obstructive pulmonary disease patients who have a predominance of type II fibers. Copyright © 2015 the American Physiological Society.

  9. Changes in oxygenation and phosphocreatine during exercise and recovery in relation to fiber types and capillary supply in human skeletal muscle

    NASA Astrophysics Data System (ADS)

    Hamaoka, Takatumi; Mizuno, Masano; Osada, Takuya; Ratkevicius, Aivaras; Nielsen, Alexander N.; Nakagawa, Yoshinao; Katsumura, Toshihito; Shimomitsu, Teruichi; Quistorff, Bjorn

    1998-01-01

    The purpose of this study was to examine the relationship between histochemical characteristics obtained from the gastrocnemius and changes in muscle energetics. Muscle oxygenation was determined by near infrared spectroscopy, and phosphocreatine (PCr) by 31-phosphorus magnetic resonance spectroscopy (31P-MRS) during a submaximal plantar flexion exercise and recovery. The relative occurrence (%) of slow-twitch fibers (ST), fast-twitch oxidative fibers (FTa), fast-twitch glycolytic fibers (FTb), and the number of capillaries per fiber (Cap/Fiber) were also determined. The sum of %ST and %FTa (%ST + %FTa) was 85.8 +/- 8.74% (mean +/- SD), while the number of Cap/Fiber was 2.52 +/- 0.63. The initial rate of deoxygenation (Ratedeoxy) at the beginning of the exercise was 2.43 +/- 0.95 %(DOT)sec-1. The time constants (Tc) for the recovery of PCr and muscle oxygenation after exercise were 22.1 +/- 6.3 sec. and 20.3 +/- 13.6 sec., respectively. The %ST + FTa, and the number of Cap/Fiber were each positively correlated to the Ratedeoxy (P < 0.05). The %ST + %FTa, and the number of Cap/Fiber were negatively correlated to the Tc for PCr recovery (P < 0.05), but not correlated to that for muscle oxygenation recovery. In conclusion, the Ratedeoxy during localized submaximal exercise, and the Tc for PCr recovery are indicators of the muscle's oxidative capacity.

  10. Changes in oxygenation and phosphocreatine during exercise and recovery in relation to fiber types and capillary supply in human skeletal muscle

    NASA Astrophysics Data System (ADS)

    Hamaoka, Takatumi; Mizuno, Masano; Osada, Takuya; Ratkevicius, Aivaras; Nielsen, Alexander N.; Nakagawa, Yoshinao; Katsumura, Toshihito; Shimomitsu, Teruichi; Quistorff, Bjorn

    1997-12-01

    The purpose of this study was to examine the relationship between histochemical characteristics obtained from the gastrocnemius and changes in muscle energetics. Muscle oxygenation was determined by near infrared spectroscopy, and phosphocreatine (PCr) by 31-phosphorus magnetic resonance spectroscopy (31P-MRS) during a submaximal plantar flexion exercise and recovery. The relative occurrence (%) of slow-twitch fibers (ST), fast-twitch oxidative fibers (FTa), fast-twitch glycolytic fibers (FTb), and the number of capillaries per fiber (Cap/Fiber) were also determined. The sum of %ST and %FTa (%ST + %FTa) was 85.8 +/- 8.74% (mean +/- SD), while the number of Cap/Fiber was 2.52 +/- 0.63. The initial rate of deoxygenation (Ratedeoxy) at the beginning of the exercise was 2.43 +/- 0.95 %(DOT)sec-1. The time constants (Tc) for the recovery of PCr and muscle oxygenation after exercise were 22.1 +/- 6.3 sec. and 20.3 +/- 13.6 sec., respectively. The %ST + FTa, and the number of Cap/Fiber were each positively correlated to the Ratedeoxy (P < 0.05). The %ST + %FTa, and the number of Cap/Fiber were negatively correlated to the Tc for PCr recovery (P < 0.05), but not correlated to that for muscle oxygenation recovery. In conclusion, the Ratedeoxy during localized submaximal exercise, and the Tc for PCr recovery are indicators of the muscle's oxidative capacity.

  11. Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology.

    PubMed

    Hsiao, Amy Y; Okitsu, Teru; Onoe, Hiroaki; Kiyosawa, Mahiro; Teramae, Hiroki; Iwanaga, Shintaroh; Kazama, Tomohiko; Matsumoto, Taro; Takeuchi, Shoji

    2015-01-01

    The proper functioning of many organs and tissues containing smooth muscles greatly depends on the intricate organization of the smooth muscle cells oriented in appropriate directions. Consequently controlling the cellular orientation in three-dimensional (3D) cellular constructs is an important issue in engineering tissues of smooth muscles. However, the ability to precisely control the cellular orientation at the microscale cannot be achieved by various commonly used 3D tissue engineering building blocks such as spheroids. This paper presents the formation of coiled spring-shaped 3D cellular constructs containing circumferentially oriented smooth muscle-like cells differentiated from dedifferentiated fat (DFAT) cells. By using the cell fiber technology, DFAT cells suspended in a mixture of extracellular proteins possessing an optimized stiffness were encapsulated in the core region of alginate shell microfibers and uniformly aligned to the longitudinal direction. Upon differentiation induction to the smooth muscle lineage, DFAT cell fibers self-assembled to coiled spring structures where the cells became circumferentially oriented. By changing the initial core-shell microfiber diameter, we demonstrated that the spring pitch and diameter could be controlled. 21 days after differentiation induction, the cell fibers contained high percentages of ASMA-positive and calponin-positive cells. Our technology to create these smooth muscle-like spring constructs enabled precise control of cellular alignment and orientation in 3D. These constructs can further serve as tissue engineering building blocks for larger organs and cellular implants used in clinical treatments.

  12. Smooth Muscle-Like Tissue Constructs with Circumferentially Oriented Cells Formed by the Cell Fiber Technology

    PubMed Central

    Hsiao, Amy Y.; Okitsu, Teru; Onoe, Hiroaki; Kiyosawa, Mahiro; Teramae, Hiroki; Iwanaga, Shintaroh; Kazama, Tomohiko; Matsumoto, Taro; Takeuchi, Shoji

    2015-01-01

    The proper functioning of many organs and tissues containing smooth muscles greatly depends on the intricate organization of the smooth muscle cells oriented in appropriate directions. Consequently controlling the cellular orientation in three-dimensional (3D) cellular constructs is an important issue in engineering tissues of smooth muscles. However, the ability to precisely control the cellular orientation at the microscale cannot be achieved by various commonly used 3D tissue engineering building blocks such as spheroids. This paper presents the formation of coiled spring-shaped 3D cellular constructs containing circumferentially oriented smooth muscle-like cells differentiated from dedifferentiated fat (DFAT) cells. By using the cell fiber technology, DFAT cells suspended in a mixture of extracellular proteins possessing an optimized stiffness were encapsulated in the core region of alginate shell microfibers and uniformly aligned to the longitudinal direction. Upon differentiation induction to the smooth muscle lineage, DFAT cell fibers self-assembled to coiled spring structures where the cells became circumferentially oriented. By changing the initial core-shell microfiber diameter, we demonstrated that the spring pitch and diameter could be controlled. 21 days after differentiation induction, the cell fibers contained high percentages of ASMA-positive and calponin-positive cells. Our technology to create these smooth muscle-like spring constructs enabled precise control of cellular alignment and orientation in 3D. These constructs can further serve as tissue engineering building blocks for larger organs and cellular implants used in clinical treatments. PMID:25734774

  13. Therapeutic angiogenesis in ischemic muscles after local injection of fragmented fibers with loaded traditional Chinese medicine

    NASA Astrophysics Data System (ADS)

    Li, Huiyan; Wan, Huiying; Xia, Tian; Chen, Maohua; Zhang, Yun; Luo, Xiaoming; Li, Xiaohong

    2015-07-01

    Therapeutic angiogenesis remains the most effective method to re-establish a proper blood flow in ischemic tissues. There is a great clinical need to identify an injectable format to achieve a well accumulation following local administration and a sustained delivery of biological factors at the ischemic sites. In the current study, fragmented nanofibers with loaded traditional Chinese medicines, astragaloside IV (AT), the main active ingredient of astragalus, and ferulic acid (FA), the main ingredient of angelica, were proposed to promote the microvessel formation after intramuscular injection into ischemic hindlimbs. Fragmented fibers with average lengths of 5 (FF-5), 20 (FF-20) and 80 μm (FF-80) were constructed by the cryocutting of aligned electrospun fibers. Their dispersion in sodium alginate solution (0.2%) indicated good injectability. After injection into the quadriceps muscles of the hindlimbs, FF-20 and FF-80 fiber fragments showed higher tissue retentions than FF-5, and around 90% of the injected doses were determined after 7 days. On a hindlimb ischemia model established by ligating the femoral arteries, intramuscular injection of the mixtures of FA-loaded and AT-loaded FF-20 fiber fragments substantially reduced the muscle degeneration with minimal fibrosis formation, significantly enhanced the neovessel formation and hindlimb perfusion in the ischemic tissues, and efficiently promoted the limb salvage with few limb losses. Along with the easy manipulation and lower invasiveness for in vivo administration, fragmented fibers should become potential drug carriers for disease treatment, wound recovery and tissue repair after local injection.

  14. Improved fatigue resistance in Gsα-deficient and aging mouse skeletal muscles due to adaptive increases in slow fibers

    PubMed Central

    Feng, Han-Zhong; Chen, Min; Weinstein, Lee S.

    2011-01-01

    Genetically modified mice with deficiency of the G protein α-subunit (Gsα) in skeletal muscle showed metabolic abnormality with reduced glucose tolerance, low muscle mass, and low contractile force, along with a fast-to-slow-fiber-type switch (Chen M, Feng HZ, Gupta D, Kelleher J, Dickerson KE, Wang J, Hunt D, Jou W, Gavrilova O, Jin JP, Weinstein LS. Am J Physiol Cell Physiol 296: C930–C940, 2009). Here we investigated a hypothesis that the switching to more slow fibers is an adaptive response with specific benefit. The results showed that, corresponding to the switch of myosin isoforms, the thin-filament regulatory proteins troponin T and troponin I both switched to their slow isoforms in the atrophic soleus muscle of 3-mo-old Gsα-deficient mice. This fiber-type switch involving coordinated changes of both thick- and thin-myofilament proteins progressed in the Gsα-deficient soleus muscles of 18- to 24-mo-old mice, as reflected by the expression of solely slow isoforms of myosin and troponin. Compared with age-matched controls, Gsα-deficient soleus muscles with higher proportion of slow fibers exhibited slower contractile and relaxation kinetics and lower developed force, but significantly increased resistance to fatigue, followed by a better recovery. Gsα-deficient soleus muscles of neonatal and 3-wk-old mice did not show the increase in slow fibers. Therefore, the fast-to-slow-fiber-type switch in Gsα deficiency at older ages was likely an adaptive response. The benefit of higher fatigue resistance in adaption to metabolic deficiency and aging provides a mechanism to sustain skeletal muscle function in diabetic patients and elderly individuals. PMID:21680879

  15. Influence of spaceflight on rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Martin, Thomas P.; Edgerton, V. Reggie; Grindeland, Richard E.

    1988-01-01

    The effect of a 7-day spaceflight (aboard NASA's SL-3) on the size and the metabolism of single fibers from several rat muscles was investigated along with the specificity of these responses as related to the muscle type and the size of fibers. It was found that the loss of mass after flight was varied from 36 percent in the soleus to 15 percent in the extensor digitorum longus. Results of histochemical analyses showed that the succinate dehydrogenase (SDH) activity in muscles of flight-exposed rats was maintained at the control levels, whereas the alpha-glycerol phosphate dehydrogenase (GPD) activity was either maintained or increased. The analyses of the metabolic profiles of ATPase, SDH, and GPD indicated that, in some muscles, there was an increase in the poportion of fast oxidative-glycolytic fibers.

  16. Mitochondrial fatty acid biosynthesis and muscle fiber plasticity in very long-chain acyl-CoA dehydrogenase-deficient mice.

    PubMed

    Tucci, Sara; Mingirulli, Nadja; Wehbe, Zeinab; Dumit, Verónica I; Kirschner, Janbernd; Spiekerkoetter, Ute

    2018-01-01

    The white skeletal muscle of very long-chain acyl-CoA-dehydrogenase-deficient (VLCAD -/- ) mice undergoes metabolic modification to compensate for defective β-oxidation in a progressive and time-dependent manner by upregulating glucose oxidation. This metabolic regulation seems to be accompanied by morphologic adaptation of muscle fibers toward the glycolytic fiber type II with the concomitant upregulation of mitochondrial fatty acid biosynthesis (mFASII) and lipoic acid biosynthesis. Dietary supplementation of VLCAD -/- mice with different medium-chain triglycerides over 1 year revealed that odd-chain species has no effect on muscle fiber switch, whereas even-chain species inhibit progressive metabolic adaptation. Our study shows that muscle may undergo adaptive mechanisms that are modulated by dietary supplementation. We describe for the first time a concomitant change of mFASII in this muscular adaptation process. © 2017 Federation of European Biochemical Societies.

  17. Circadian force and EMG activity in hindlimb muscles of rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Hodgson, J. A.; Wichayanuparp, S.; Recktenwald, M. R.; Roy, R. R.; McCall, G.; Day, M. K.; Washburn, D.; Fanton, J. W.; Kozlovskaya, I.; Edgerton, V. R.; hide

    2001-01-01

    Continuous intramuscular electromyograms (EMGs) were recorded from the soleus (Sol), medial gastrocnemius (MG), tibialis anterior (TA), and vastus lateralis (VL) muscles of Rhesus during normal cage activity throughout 24-h periods and also during treadmill locomotion. Daily levels of MG tendon force and EMG activity were obtained from five monkeys with partial datasets from three other animals. Activity levels correlated with the light-dark cycle with peak activities in most muscles occurring between 08:00 and 10:00. The lowest levels of activity generally occurred between 22:00 and 02:00. Daily EMG integrals ranged from 19 mV/s in one TA muscle to 3339 mV/s in one Sol muscle: average values were 1245 (Sol), 90 (MG), 65 (TA), and 209 (VL) mV/s. The average Sol EMG amplitude per 24-h period was 14 microV, compared with 246 microV for a short burst of locomotion. Mean EMG amplitudes for the Sol, MG, TA, and VL during active periods were 102, 18, 20, and 33 microV, respectively. EMG amplitudes that approximated recruitment of all fibers within a muscle occurred for 5-40 s/day in all muscles. The duration of daily activation was greatest in the Sol [151 +/- 45 (SE) min] and shortest in the TA (61 +/- 19 min). The results show that even a "postural" muscle such as the Sol was active for only approximately 9% of the day, whereas less active muscles were active for approximately 4% of the day. MG tendon forces were generally very low, consistent with the MG EMG data but occasionally reached levels close to estimates of the maximum force generating potential of the muscle. The Sol and TA activities were mutually exclusive, except at very low levels, suggesting very little coactivation of these antagonistic muscles. In contrast, the MG activity usually accompanied Sol activity suggesting that the MG was rarely used in the absence of Sol activation. The results clearly demonstrate a wide range of activation levels among muscles of the same animal as well as among different

  18. Macrophage activation and muscle remodeling at myotendinous junctions after modifications in muscle loading.

    PubMed Central

    St Pierre, B. A.; Tidball, J. G.

    1994-01-01

    Modifications in muscle loading have been reported previously to result in increased numbers of mononucleated cells and changes in myofibril organization at myotendinous junctions (MTJs). The goals of this study were to determine the identity of those mononucleated cells and to examine the relationships between changes in their structure, location, and number with structural aspects of remodeling at MTJs experiencing modified loading. Soleus muscles from rats subjected to 10 days of hindlimb suspension were analyzed 0, 2, 4, and 7 days after return to weight bearing. Immunohistochemistry showed that ED1+, ED2+ and Ia+ macrophages were present at the MTJ and microtendon of control muscle. After reloading, ED2+ macrophages increased in number and size at MTJs and microtendons, indicating their activation. ED1+ cells showed no change in size or number whereas Ia+ cells were increased in size at day 7 of reloading. Electron microscopic observations showed that mononucleated cells near MTJs of control or suspended muscle were not highly active in protein synthesis or secretion. However, in reloaded muscle, mononucleated cells were found to be in close proximity to MTJs and to contain a high concentration of organelles associated with protein secretion. During these stages of reloading, extensive remodeling of myofibril-membrane associations occurred and nascent sarcomeres appeared in the MTJ regions of muscle fibers. Immunohistochemistry showed that during these stages of nascent sarcomere formation, there was renewed expression of developmental myosin heavy chain at MTJs, with this heavy chain appearing most prominently at the MTJ at day 7 of reloading. The activation and increased numbers of macrophages at MTJs and the close apposition of secretory cells to the MTJ membrane during remodeling lead us to propose that macrophage-derived factors may influence remodeling of MTJs in muscles experiencing modified loading. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5

  19. Bifunctional Rhodamine Probes of Myosin Regulatory Light Chain Orientation in Relaxed Skeletal Muscle Fibers

    PubMed Central

    Brack, Andrew S.; Brandmeier, Birgit D.; Ferguson, Roisean E.; Criddle, Susan; Dale, Robert E.; Irving, Malcolm

    2004-01-01

    The orientation of the regulatory light chain (RLC) region of the myosin heads in relaxed skinned fibers from rabbit psoas muscle was investigated by polarized fluorescence from bifunctional rhodamine (BR) probes cross-linking pairs of cysteine residues introduced into the RLC. Pure 1:1 BR-RLC complexes were exchanged into single muscle fibers in EDTA rigor solution for 30 min at 30°C; ∼60% of the native RLC was removed and stoichiometrically replaced by BR-RLC, and >85% of the BR-RLC was located in the sarcomeric A-bands. The second- and fourth-rank order parameters of the orientation distributions of BR dipoles linking RLC cysteine pairs 100-108, 100-113, 108-113, and 104-115 were calculated from polarized fluorescence intensities, and used to determine the smoothest RLC orientation distribution—the maximum entropy distribution—consistent with the polarized fluorescence data. Maximum entropy distributions in relaxed muscle were relatively broad. At the peak of the distribution, the “lever” axis, linking Cys707 and Lys843 of the myosin heavy chain, was at 70–80° to the fiber axis, and the “hook” helix (Pro830–Lys843) was almost coplanar with the fiber and lever axes. The temperature and ionic strength of the relaxing solution had small but reproducible effects on the orientation of the RLC region. PMID:15041671

  20. Reduced Appendicular Lean Body Mass, Muscle Strength, and Size of Type II Muscle Fibers in Patients with Spondyloarthritis versus Healthy Controls: A Cross-Sectional Study.

    PubMed

    Røren Nordén, Kristine; Dagfinrud, Hanne; Løvstad, Amund; Raastad, Truls

    Introduction . The purpose of this study was to investigate body composition, muscle function, and muscle morphology in patients with spondyloarthritis (SpA). Methods . Ten male SpA patients (mean ± SD age 39 ± 4.1 years) were compared with ten healthy controls matched for sex, age, body mass index, and self-reported level of physical exercise. Body composition was measured by dual energy X-ray absorptiometry. Musculus quadriceps femoris (QF) strength was assessed by maximal isometric contractions prior to test of muscular endurance. Magnetic resonance imaging of QF was used to measure muscle size and calculate specific muscle strength. Percutaneous needle biopsy samples were taken from m. vastus lateralis . Results . SpA patients presented with significantly lower appendicular lean body mass (LBM) ( p = 0.02), but there was no difference in bone mineral density, fat mass, or total LBM. Absolute QF strength was significantly lower in SpA patients ( p = 0.03) with a parallel trend for specific strength ( p = 0.08). Biopsy samples from the SpA patients revealed significantly smaller cross-sectional area (CSA) of type II muscle fibers ( p = 0.04), but no difference in CSA type I fibers. Conclusions . Results indicate that the presence of SpA disease is associated with reduced appendicular LBM, muscle strength, and type II fiber CSA.

  1. Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure

    NASA Technical Reports Server (NTRS)

    Massie, B. M.; Simonini, A.; Sahgal, P.; Wells, L.; Dudley, G. A.

    1996-01-01

    OBJECTIVES. The present study was undertaken to further characterize changes in skeletal muscle morphology and histochemistry in congestive heart failure and to determine the relation of these changes to abnormalities of systemic and local muscle exercise capacity. BACKGROUND. Abnormalities of skeletal muscle appear to play a role in the limitation of exercise capacity in congestive heart failure, but information on the changes in muscle morphology and biochemistry and their relation to alterations in muscle function is limited. METHODS. Eighteen men with predominantly mild to moderate congestive heart failure (mean +/- SEM New York Heart Association functional class 2.6 +/- 0.2, ejection fraction 24 +/- 2%) and eight age- and gender-matched sedentary control subjects underwent measurements of peak systemic oxygen consumption (VO2) during cycle ergometry, resistance to fatigue of the quadriceps femoris muscle group and biopsy of the vastus lateralis muscle. RESULTS. Peak VO2 and resistance to fatigue were lower in the patients with heart failure than in control subjects (15.7 +/- 1.2 vs. 25.1 +/- 1.5 ml/min-kg and 63 +/- 2% vs. 85 +/- 3%, respectively, both p < 0.001). Patients had a lower proportion of slow twitch, type I fibers than did control subjects (36 +/- 3% vs. 46 +/- 5%, p = 0.048) and a higher proportion of fast twitch, type IIab fibers (18 +/- 3% vs. 7 +/- 2%, p = 0.004). Fiber cross-sectional area was smaller, and single-fiber succinate dehydrogenase activity, a mitochondrial oxidative marker, was lower in patients (both p < or = 0.034). Likewise, the ratio of average fast twitch to slow twitch fiber cross-sectional area was lower in patients (0.780 +/- 0.06 vs. 1.05 +/- 0.08, p = 0.019). Peak VO2 was strongly related to integrated succinate dehydrogenase activity in patients (r = 0.896, p = 0.001). Peak VO2, resistance to fatigue and strength also correlated significantly with several measures of fiber size, especially of fast twitch fibers, in

  2. Alterations in intrinsic mitochondrial function with aging are fiber type-specific and do not explain differential atrophy between muscles.

    PubMed

    Picard, Martin; Ritchie, Darmyn; Thomas, Melissa M; Wright, Kathryn J; Hepple, Russell T

    2011-12-01

    To determine whether mitochondrial dysfunction is causally related to muscle atrophy with aging, we examined respiratory capacity, H(2) O(2) emission, and function of the mitochondrial permeability transition pore (mPTP) in permeabilized myofibers prepared from four rat muscles that span a range of fiber type and degree of age-related atrophy. Muscle atrophy with aging was greatest in fast-twitch gastrocnemius (Gas) muscle (-38%), intermediate in both the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscles (-21%), and non-existent in adductor longus (AL) muscle (+47%). In contrast, indices of mitochondrial dysfunction did not correspond to this differential degree of atrophy. Specifically, despite higher protein expression for oxidative phosphorylation (oxphos) system in fast Gas and EDL, state III respiratory capacity per myofiber wet weight was unchanged with aging, whereas the slow Sol showed proportional decreases in oxphos protein, citrate synthase activity, and state III respiration. Free radical leak (H(2) O(2) emission per O(2) flux) under state III respiration was higher with aging in the fast Gas, whereas state II free radical leak was higher in the slow AL. Only the fast muscles had impaired mPTP function with aging, with lower mitochondrial calcium retention capacity in EDL and shorter time to mPTP opening in Gas and EDL. Collectively, our results underscore that the age-related changes in muscle mitochondrial function depend largely upon fiber type and are unrelated to the severity of muscle atrophy, suggesting that intrinsic changes in mitochondrial function are unlikely to be causally involved in aging muscle atrophy. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  3. Protein Supplementation Augments Muscle Fiber Hypertrophy but Does Not Modulate Satellite Cell Content During Prolonged Resistance-Type Exercise Training in Frail Elderly.

    PubMed

    Dirks, Marlou L; Tieland, Michael; Verdijk, Lex B; Losen, Mario; Nilwik, Rachel; Mensink, Marco; de Groot, Lisette C P G M; van Loon, Luc J C

    2017-07-01

    Protein supplementation increases gains in lean body mass following prolonged resistance-type exercise training in frail older adults. We assessed whether the greater increase in lean body mass can be attributed to muscle fiber type specific hypertrophy with concomitant changes in satellite cell (SC) content. A total of 34 frail elderly individuals (77 ± 1 years, n = 12 male adults) participated in this randomized, double-blind, placebo-controlled trial with 2 arms in parallel. Participants performed 24 weeks of progressive resistance-type exercise training (2 sessions per week) during which they were supplemented twice-daily with milk protein (2 × 15 g) or a placebo. Muscle biopsies were taken at baseline, and after 12 and 24 weeks of intervention, to determine type I and type II muscle fiber specific cross-sectional area (CSA), SC content, and myocellular characteristics. In the placebo group, a trend for a 20% ± 11% increase in muscle fiber CSA was observed in type II fibers only (P = .051), with no increase in type I muscle fiber CSA. In the protein group, type I and II muscle fiber CSA increased by 23% ± 7% and 34% ± 10% following 6 months of training, respectively (P < .01). Myonuclear domain size increased over time in both groups and fiber types (P < .001), with no significant differences between groups (P > .05). No changes in myonuclear content and SC contents were observed over time in either group (both P > .05). Regression analysis showed that changes in myonuclear content and domain size are predictive of muscle fiber hypertrophy. Protein supplementation augments muscle fiber hypertrophy following prolonged resistance-type exercise training in frail older people, without changes in myonuclear and SC content. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  4. Effect of LKB1 deficiency on mitochondrial content, fiber type, and muscle performance in the mouse diaphragm

    PubMed Central

    Brown, Jacob D.; Hancock, Chad R.; Mongillo, Anthony D.; Barton, J. Benjamin; DiGiovanni, Ryan A.; Parcell, Allen C.; Winder, William W.; Thomson, David M.

    2010-01-01

    Aim The Liver Kinase B1 (LKB1)/AMP-Activated Protein Kinase (AMPK) signaling pathway is a major regulator of skeletal muscle metabolic processes. During exercise, LKB1-mediated phosphorylation of AMPK leads to its activation, promoting mitochondrial biogenesis and glucose transport, among other effects. The roles of LKB1 and AMPK have not been fully characterized in the diaphragm. Methods Two methods of AMPK activation were used to characterize LKB1/AMPK signaling in diaphragms from muscle-specific LKB1 knockout (KO) and littermate control mice: (1) acute injection of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and (2) 5-min direct electrical stimulation of the diaphragm. Diaphragms were excised 60 minutes post-AICAR injection and immediately after electrical stimulation. Results AMPK phosphorylation increased with AICAR and electrical stimulation in control but not KO mice. Acetyl CoA carboxylase phosphorylation increased with AICAR in control but not KO mice, but increased in both genotypes with electrical stimulation. While the majority of mitochondrial protein levels were lower in KO diaphragms, uncoupling protein 3, complex I, and cytochrome oxidase IV protein levels were not different between genotypes. KO diaphragms have a lower percentage of IIx fibers and an elevated percentage of IIb fibers when compared to control diaphragms. While in vitro peak force generation was similar between genotypes, KO diaphragms fatigued more quickly and had an impaired ability to recover. Conclusion LKB1 regulates AMPK phosphorylation, mitochondrial protein expression, fiber type distribution, as well as recovery of the diaphragm from fatigue. PMID:21073663

  5. Chloride Fluxes in Isolated Dialyzed Barnacle Muscle Fibers

    PubMed Central

    DiPolo, R.

    1972-01-01

    Chloride outflux and influx has been studied in single isolated muscle fibers from the giant barnacle under constant internal composition by means of a dialysis perfusion technique. Membrane potential was continually recorded. The chloride outfluxes and influxes were 143 and 144 pmoles/cm2-sec (mean resting potential: 58 mv, temperature: 22°–24°C) with internal and external chloride concentrations of 30 and 541 mM, respectively. The chloride conductance calculated from tracer measurements using constant field assumptions is about fourfold greater than that calculated from published electrical data. Replacing 97% of the external chloride ions by propionate reduces the chloride efflux by 51%. Nitrate ions applied either to the internal or external surface of the membrane slows the chloride efflux. The external pH dependence of the chloride efflux follows the external pH dependence of the membrane conductance, in the range pH 3.9–4.7, increasing with decreasing pH. In the range pH 5–9, the chloride efflux increased with increasing pH, in a manner similar to that observed in frog muscle fibers. The titration curve for internal pH changes in the range 4.0–7.0 was quantitatively much different from that for external pH change, indicating significant asymmetry in the internal and external pH dependence of the chloride efflux. PMID:5074810

  6. Silent calcium channels in skeletal muscle fibers of the crustacean Atya lanipes.

    PubMed

    Monterrubio, J; Lizardi, L; Zuazaga, C

    2000-01-01

    The superficial (tonic) abdominal flexor muscles of Atya lanipes do not generate Ca(2+) action potentials when depolarized and have no detectable inward Ca(2+) current. These fibers, however, are strictly dependent on Ca(2+) influx for contraction, suggesting that they depend on Ca(2+)-induced Ca(2+) release for contractile activation. The nature of the communication between Ca(2+) channels in the sarcolemmal/tubular membrane and Ca(2+) release channels in the sarcoplasmic reticulum in this crustacean muscle was investigated. The effects of dihydropyridines on tension generation and the passive electrical response were examined in current-clamped fibers: Bay K 8644 enhanced tension about 100% but did not alter the passive electrical response; nifedipine inhibited tension by about 70%. Sr(2+) and Ba(2+) action potentials could be elicited in Ca(2+)-free solutions. The spikes generated by these divalent cations were abolished by nifedipine. As the Sr(2+) or Ba(2+) concentrations were increased, the amplitudes of the action potentials and their maximum rate of rise, V(max), increased and tended towards saturation. Three-microelectrode voltage-clamp experiments showed that even at high (138 mm) extracellular Ca(2+) concentration the channels were silent, i.e., no inward Ca(2+) current was detected. In Ca(2+)-free solutions, inward currents carried by 138 mm Sr(2+) or Ba(2+) were observed. The currents activated at voltages above -40 mV and peaked at about 0 mV. This voltage-activation profile and the sensitivity of the channels to dihydropyridines indicate that they resemble L-type Ca(2+) channels. Peak inward current density values were low, ca. -33 microA/cm(2) for Sr(2+) and -14 microA/cm(2) for Ba(2+), suggesting that Ca(2+) channels are present at a very low density. It is concluded that Ca(2+)-induced Ca(2+) release in this crustacean muscle operates with an unusually high gain: Ca(2+) influx through the silent Ca(2+) channels is too low to generate a macroscopic

  7. HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology.

    PubMed

    Favier, F B; Britto, F A; Freyssenet, D G; Bigard, X A; Benoit, H

    2015-12-01

    Skeletal muscle is a metabolically active tissue and the major body protein reservoir. Drop in ambient oxygen pressure likely results in a decrease in muscle cells oxygenation, reactive oxygen species (ROS) overproduction and stabilization of the oxygen-sensitive hypoxia-inducible factor (HIF)-1α. However, skeletal muscle seems to be quite resistant to hypoxia compared to other organs, probably because it is accustomed to hypoxic episodes during physical exercise. Few studies have observed HIF-1α accumulation in skeletal muscle during ambient hypoxia probably because of its transient stabilization. Nevertheless, skeletal muscle presents adaptations to hypoxia that fit with HIF-1 activation, although the exact contribution of HIF-2, I kappa B kinase and activating transcription factors, all potentially activated by hypoxia, needs to be determined. Metabolic alterations result in the inhibition of fatty acid oxidation, while activation of anaerobic glycolysis is less evident. Hypoxia causes mitochondrial remodeling and enhanced mitophagy that ultimately lead to a decrease in ROS production, and this acclimatization in turn contributes to HIF-1α destabilization. Likewise, hypoxia has structural consequences with muscle fiber atrophy due to mTOR-dependent inhibition of protein synthesis and transient activation of proteolysis. The decrease in muscle fiber area improves oxygen diffusion into muscle cells, while inhibition of protein synthesis, an ATP-consuming process, and reduction in muscle mass decreases energy demand. Amino acids released from muscle cells may also have protective and metabolic effects. Collectively, these results demonstrate that skeletal muscle copes with the energetic challenge imposed by O2 rarefaction via metabolic optimization.

  8. Chloride currents from the transverse tubular system in adult mammalian skeletal muscle fibers

    PubMed Central

    DiFranco, Marino; Herrera, Alvaro

    2011-01-01

    Chloride fluxes are the main contributors to the resting conductance of mammalian skeletal muscle fibers. ClC-1, the most abundant chloride channel isoform in this preparation, is believed to be responsible for this conductance. However, the actual distribution of ClC-1 channels between the surface and transverse tubular system (TTS) membranes has not been assessed in intact muscle fibers. To investigate this issue, we voltageclamped enzymatically dissociated short fibers using a two-microelectrode configuration and simultaneously recorded chloride currents (ICl) and di-8-ANEPPS fluorescence signals to assess membrane potential changes in the TTS. Experiments were conducted in conditions that blocked all but the chloride conductance. Fibers were equilibrated with 40 or 70 mM intracellular chloride to enhance the magnitude of inward ICl, and the specific ClC-1 blocker 9-ACA was used to eliminate these currents whenever necessary. Voltage-dependent di-8-ANEPPS signals and ICl acquired before (control) and after the addition of 9-ACA were comparatively assessed. Early after the onset of stimulus pulses, di-8-ANEPPS signals under control conditions were smaller than those recorded in the presence of 9-ACA. We defined as attenuation the normalized time-dependent difference between these signals. Attenuation was discovered to be ICl dependent since its magnitude varied in close correlation with the amplitude and time course of ICl. While the properties of ICl, and those of the attenuation seen in optical records, could be simultaneously predicted by model simulations when the chloride permeability (PCl) at the surface and TTS membranes were approximately equal, the model failed to explain the optical data if PCl was precluded from the TTS membranes. Since the ratio between the areas of TTS membranes and the sarcolemma is large in mammalian muscle fibers, our results demonstrate that a significant fraction of the experimentally recorded ICl arises from TTS contributions

  9. Effect of the architecture of the left ventricle on the speed of the excitation wave in muscle fibers

    NASA Astrophysics Data System (ADS)

    Nezlobinsky, T. V.; Pravdin, S. F.; Katsnelson, L. B.; Solovyova, O. E.

    2016-07-01

    It is known that preferential paths for the propagation of an electrical excitation wave in the human ventricular myocardium are associated with muscle fibers in tissue. The speed of the excitation wave along a fiber is several times higher than that across the direction of the fiber. To estimate the effect of the architecture and anisotropy of the myocardium of the left ventricle on the process of its electrical activation, we have studied the relation between the speed of the electrical excitation wave in a one-dimensional isolated myocardial fiber consisting of sequentially coupled cardiomyocytes and in an identical fiber located in the wall of a threedimensional anatomical model of the left ventricle. It has been shown that the speed of a wavefront along the fiber in the three-dimensional myocardial tissue is much higher than that in the one-dimensional fiber. The acceleration of the signal is due to the rotation of directions of fibers in the wall and to the position of the excitation wavefront with respect to the direction of this fiber. The observed phenomenon is caused by the approach of the excitable tissue with rotational anisotropy in its properties to a pseudoisotropic tissue.

  10. Intramyocellular lipid dependence on skeletal muscle fiber type and orientation characterized by diffusion tensor imaging and 1H-MRS

    NASA Astrophysics Data System (ADS)

    Valaparla, Sunil K.; Gao, Feng; Abdul-Ghani, Muhammad; Clarke, Geoffrey D.

    2014-03-01

    When muscle fibers are aligned with the B0 field, intramyocellular lipids (IMCL), important for providing energy during physical activity, can be resolved in proton magnetic resonance spectra (1H-MRS). Various muscles of the leg differ significantly in their proportion of fibers and angular distribution. This study determined the influence of muscle fiber type and orientation on IMCL using 1H-MRS and diffusion tensor imaging (DTI). Muscle fiber orientation relative to B0 was estimated by pennation angle (PA) measurements from DTI, providing orientation-specific extramyocellular lipid (EMCL) chemical shift data that were used for subject-specific IMCL quantification. Vastus lateralis (VL), tibialis anterior (TA) and soleus (SO) muscles of 6 healthy subjects (21-40 yrs) were studied on a Siemens 3T MRI system with a flex 4-channel coil. 1H-MRS were acquired using stimulated echo acquisition mode (STEAM, TR=3s, TE=270ms). DTI was performed using single shot EPI (b=600s/mm2, 30 directions, TR=4.5s, TE=82ms, and ten×5mm slices) with center slice indexed to the MRS voxel. The average PA's measured from ROI analysis of primary eigenvectors were PA=19.46+/-5.43 for unipennate VL, 15.65+/-3.73 for multipennate SO, and 7.04+/-3.34 for bipennate TA. Chemical shift (CS) was calculated using [3cos2θ-1] dependence: 0.17+/-0.02 for VL, 0.18+/-0.01 for SO and 0.19+/-0.004 ppm for TA. IMCL-CH2 concentrations from spectral analysis were 12.77+/-6.3 for VL, 3.07+/-1.63 for SO and 0.27+/-0.08 mmol/kg ww for TA. Small PA's were measured in TA and large CS with clear separation between EMCL and IMCL peaks were observed. Larger variations in PA were measured VL and SO resulting in an increased overlap of the EMCL on IMCL peaks.

  11. AHNAK1 and AHNAK2 are costameric proteins: AHNAK1 affects transverse skeletal muscle fiber stiffness

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Marg, Andreas, E-mail: andreas.marg@mdc-berlin.de; Haase, Hannelore; Neumann, Tanja

    2010-10-08

    Research highlights: {yields} AHNAK1 and AHNAK2 are costameric proteins. {yields} Intact membrane repair in AHNAK1-deficient mice. {yields} AHNAK1{sup -/-} single fibers have a higher transverse stiffness. -- Abstract: The AHNAK scaffold PDZ-protein family is implicated in various cellular processes including membrane repair; however, AHNAK function and subcellular localization in skeletal muscle are unclear. We used specific AHNAK1 and AHNAK2 antibodies to analyzed the detailed localization of both proteins in mouse skeletal muscle. Co-localization of AHNAK1 and AHNAK2 with vinculin clearly demonstrates that both proteins are components of the costameric network. In contrast, no AHNAK expression was detected in the T-tubulemore » system. A laser wounding assay with AHNAK1-deficient fibers suggests that AHNAK1 is not involved in membrane repair. Using atomic force microscopy (AFM), we observed a significantly higher transverse stiffness of AHNAK1{sup -/-} fibers. These findings suggest novel functions of AHNAK proteins in skeletal muscle.« less

  12. GSNOR Deficiency Enhances In Situ Skeletal Muscle Strength, Fatigue Resistance, and RyR1 S-Nitrosylation Without Impacting Mitochondrial Content and Activity

    PubMed Central

    Moon, Younghye; Cao, Yenong; Zhu, Jingjing; Xu, Yuanyuan; Balkan, Wayne; Buys, Emmanuel S.; Diaz, Francisca; Kerrick, W. Glenn; Hare, Joshua M.

    2017-01-01

    Abstract Aim: Nitric oxide (NO) plays important, but incompletely defined roles in skeletal muscle. NO exerts its regulatory effects partly though S-nitrosylation, which is balanced by denitrosylation by enzymes such as S-nitrosoglutathione reductase (GSNOR), whose functions in skeletal muscle remain to be fully deciphered. Results: GSNOR null (GSNOR−/−) tibialis anterior (TA) muscles showed normal growth and were stronger and more fatigue resistant than controls in situ. However, GSNOR−/− lumbrical muscles showed normal contractility and Ca2+ handling in vitro, suggesting important differences in GSNOR function between muscles or between in vitro and in situ environments. GSNOR−/− TA muscles exhibited normal mitochondrial content, and capillary densities, but reduced type IIA fiber content. GSNOR inhibition did not impact mitochondrial respiratory complex I, III, or IV activities. These findings argue that enhanced GSNOR−/− TA contractility is not driven by changes in mitochondrial content or activity, fiber type, or blood vessel density. However, loss of GSNOR led to RyR1 hypernitrosylation, which is believed to increase muscle force output under physiological conditions. cGMP synthesis by soluble guanylate cyclase (sGC) was decreased in resting GSNOR−/− muscle and was more responsive to agonist (DETANO, BAY 41, and BAY 58) stimulation, suggesting that GSNOR modulates cGMP production in skeletal muscle. Innovation: GSNOR may act as a “brake” on skeletal muscle contractile performance under physiological conditions by modulating nitrosylation/denitrosylation balance. Conclusions: GSNOR may play important roles in skeletal muscle contractility, RyR1 S-nitrosylation, fiber type specification, and sGC activity. Antioxid. Redox Signal. 26, 165–181. PMID:27412893

  13. Relationship between innervation zone width and mean muscle fiber conduction velocity during a sustained isometric contraction.

    PubMed

    Ye, X; Beck, T W; Wages, N P

    2015-03-01

    To examine the relationship between the biceps brachii muscle innervation zone (IZ) width and the mean muscle fiber conduction velocity (MFCV) during a sustained isometric contraction. Fifteen healthy men performed a sustained isometric elbow flexion exercise at their 60% maximal voluntary contraction (MVC) until they could not maintain the target force. Mean MFCV was estimated through multichannel surface electromyographic recordings from a linear electrode array. Before exercise, IZ width was quantified. Separate non-parametric one-way analyses of variance (ANOVAs) were used to examine whether there was a difference in each mean MFCV variable among groups with different IZ width. In addition, separate bivariate correlations were also performed to examine the relationships between the IZ width and the mean MFCV variables during the fatiguing exercise. There was a significant difference in the percent decline of mean MFCV (%ΔMFCV) among groups with different IZ width (χ(2) (3)=11.571, p=0.009). In addition, there was also a significant positive relationship between the IZ width and the %ΔMFCV (Kendall's tau= 0.807; p<0.001). We believe that such relationship is likely influenced by both muscle fiber size and the muscle fiber type composition.

  14. Platelet-Derived Growth Factor BB Influences Muscle Regeneration in Duchenne Muscle Dystrophy.

    PubMed

    Piñol-Jurado, Patricia; Gallardo, Eduard; de Luna, Noemi; Suárez-Calvet, Xavier; Sánchez-Riera, Carles; Fernández-Simón, Esther; Gomis, Clara; Illa, Isabel; Díaz-Manera, Jordi

    2017-08-01

    Duchenne muscular dystrophy (DMD) is characterized by a progressive loss of muscle fibers, and their substitution by fibrotic and adipose tissue. Many factors contribute to this process, but the molecular pathways related to regeneration and degeneration of muscle are not completely known. Platelet-derived growth factor (PDGF)-BB belongs to a family of growth factors that regulate proliferation, migration, and differentiation of mesenchymal cells. The role of PDGF-BB in muscle regeneration in humans has not been studied. We analyzed the expression of PDGF-BB in muscle biopsy samples from controls and patients with DMD. We performed in vitro experiments to understand the effects of PDGF-BB on myoblasts involved in the pathophysiology of muscular dystrophies and confirmed our results in vivo by treating the mdx murine model of DMD with repeated i.m. injections of PDGF-BB. We observed that regenerating and necrotic muscle fibers in muscle biopsy samples from DMD patients expressed PDGF-BB. In vitro, PDGF-BB attracted myoblasts and activated their proliferation. Analysis of muscles from the animals treated with PDGF-BB showed an increased population of satellite cells and an increase in the number of regenerative fibers, with a reduction in inflammatory infiltrates, compared with those in vehicle-treated mice. Based on our results, PDGF-BB may play a protective role in muscular dystrophies by enhancing muscle regeneration through activation of satellite cell proliferation and migration. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, Hsu-Pin; Hsu, Shu-Yuan; Wu, Wen-Ai

    Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB{sup +/−} mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species.more » The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity.« less

  16. Gut microbiota can transfer fiber characteristics and lipid metabolic profiles of skeletal muscle from pigs to germ-free mice.

    PubMed

    Yan, Honglin; Diao, Hui; Xiao, Yi; Li, Wenxia; Yu, Bing; He, Jun; Yu, Jie; Zheng, Ping; Mao, Xiangbing; Luo, Yuheng; Zeng, Benhua; Wei, Hong; Chen, Daiwen

    2016-08-22

    Obesity causes changes in microbiota composition, and an altered gut microbiota can transfer obesity-associated phenotypes from donors to recipients. Obese Rongchang pigs (RP) exhibited distinct fiber characteristics and lipid metabolic profiles in their muscle compared with lean Yorkshire pigs (YP). However, whether RP have a different gut microbiota than YP and whether there is a relationship between the microbiota and muscle properties are poorly understood. The present study was conducted to test whether the muscle properties can be transferred from pigs to germ-free (GF) mice. High-throughput pyrosequencing confirms the presence of distinct core microbiota between pig breeds, with alterations in taxonomic distribution and modulations in β diversity. RP displayed a significant higher Firmicutes/Bacteroidetes ratio and apparent genera differences compared with YP. Transplanting the porcine microbiota into GF mice replicated the phenotypes of the donors. RP and their GF mouse recipients exhibited a higher body fat mass, a higher slow-contracting fiber proportion, a decreased fiber size and fast IIb fiber percentage, and enhanced lipogenesis in the gastrocnemius muscle. Furthermore, the gut microbiota composition of colonized mice shared high similarity with their donor pigs. Taken together, the gut microbiota of obese pigs intrinsically influences skeletal muscle development and the lipid metabolic profiles.

  17. Slow recovery of the impaired fatigue resistance in postunloading mouse soleus muscle corresponding to decreased mitochondrial function and a compensatory increase in type I slow fibers

    PubMed Central

    Feng, Han-Zhong; Chen, Xuequn; Malek, Moh H.

    2015-01-01

    Unloading or disuse rapidly results in skeletal muscle atrophy, switching to fast-type fibers, and decreased resistance to fatigue. The recovery process is of major importance in rehabilitation for various clinical conditions. Here we studied mouse soleus muscle during 60 days of reloading after 4 wk of hindlimb suspension. Unloading produced significant atrophy of soleus muscle with decreased contractile force and fatigue resistance, accompanied by switches of myosin isoforms from IIa to IIx and IIb and fast troponin T to more low-molecular-weight splice forms. The total mass, fiber size, and contractile force of soleus muscle recovered to control levels after 15 days of reloading. However, the fatigue resistance showed a trend of worsening during this period with significant infiltration of inflammatory cells at days 3 and 7, indicating reloading injuries that were accompanied by active regeneration with upregulations of filamin-C, αB-crystallin, and desmin. The fatigue resistance partially recovered after 30–60 days of reloading. The expression of peroxisome proliferator-activated receptor γ coactivator 1α and mitofusin-2 showed changes parallel to that of fatigue resistance after unloading and during reloading, suggesting a causal role of decreased mitochondrial function. Slow fiber contents in the soleus muscle were increased after 30–60 days of reloading to become significantly higher than the normal level, indicating a secondary adaption to compensate for the slow recovery of fatigue resistance. PMID:26447205

  18. Unexpected dependence of RyR1 splice variant expression in human lower limb muscles on fiber-type composition.

    PubMed

    Willemse, Hermia; Theodoratos, Angelo; Smith, Paul N; Dulhunty, Angela F

    2016-02-01

    The skeletal muscle ryanodine receptor Ca(2+) release channel (RyR1), essential for excitation-contraction (EC) coupling, demonstrates a known developmentally regulated alternative splicing in the ASI region. We now find unexpectedly that the expression of the splice variants is closely related to fiber type in adult human lower limb muscles. We examined the distribution of myosin heavy chain isoforms and ASI splice variants in gluteus minimus, gluteus medius and vastus medialis from patients aged 45 to 85 years. There was a strong positive correlation between ASI(+)RyR1 and the percentage of type 2 fibers in the muscles (r = 0.725), and a correspondingly strong negative correlation between the percentages of ASI(+)RyR1 and percentage of type 1 fibers. When the type 2 fiber data were separated into type 2X and type 2A, the correlation with ASI(+)RyR1 was stronger in type 2X fibers (r = 0.781) than in type 2A fibers (r = 0.461). There was no significant correlation between age and either fiber-type composition or ASI(+)RyR1/ASI(-)RyR1 ratio. The results suggest that the reduced expression of ASI(-)RyR1 during development may reflect a reduction in type 1 fibers during development. Preferential expression of ASI(-) RyR1, having a higher gain of in Ca(2+) release during EC coupling than ASI(+)RyR1, may compensate for the reduced terminal cisternae volume, fewer junctional contacts and reduced charge movement in type 1 fibers.

  19. Regulation of gene expression mediating indeterminate muscle growth in teleosts.

    PubMed

    Ahammad, A K Shakur; Asaduzzaman, Md; Asakawa, Shuichi; Watabe, Shugo; Kinoshita, Shigeharu

    2015-08-01

    Teleosts are unique among vertebrates due to their indeterminate muscle growth, i.e., continued production of neonatal muscle fibers until death. However, the molecular mechanism(s) underlying this property is unknown. Here, we focused on the torafugu (Takifugu rubripes) myosin heavy chain gene, MYHM2528-1, which is specifically expressed in neonatal muscle fibers produced by indeterminate muscle growth. We examined the flanking region of MYHM2528-1 through an in vivo reporter assay using zebrafish (Danio rerio) and identified a 2100 bp 5'-flanking sequence that contained sufficient promoter activity to allow specific gene expression. The effects of enhanced promoter activity were observed at the outer region of the fast muscle and the dorsal edge of slow muscle in zebrafish larvae. At the juvenile stage, the promoter was specifically activated in small diameter muscle fibers scattered throughout fast muscle and in slow muscle near the septum separating slow and fast muscles. This spatio-temporal promoter activity overlapped with known myogenic zones involved in teleost indeterminate muscle growth. A deletion mutant analysis revealed that the -2100 to -600 bp 5'flanking sequence of MYHM2528-1 is essential for promoter activity. This region contains putative binding sites for several representative myogenesis-related transcription factors and nuclear factor of activated T-cell (NFAT), a transcription activator involved in regeneration of mammalian adult skeletal muscle. A significant reduction in the promoter activity of the MYHM2528-1 deletion constructs was observed in accordance with a reduction in the number of these binding sites, suggesting the involvement of specific transcription factors in indeterminate muscle growth. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Inverse relationship between exercise economy and oxidative capacity in muscle.

    PubMed

    Hunter, Gary R; Bamman, Marcas M; Larson-Meyer, D Enette; Joanisse, Denis R; McCarthy, John P; Blaudeau, Tamilane E; Newcomer, Bradley R

    2005-08-01

    An inverse relationship has been shown between running and cycling exercise economy and maximum oxygen uptake (VO2max). The purposes were: 1) determine the relationship between walking economy and VO2max; and 2) determine the relationship between muscle metabolic economy and muscle oxidative capacity and fiber type. Subjects were 77 premenopausal normal weight women. Walking economy (1/VO2max) was measured at 3 mph and VO2max during graded treadmill test. Muscle oxidative phosphorylation rate (OxPhos), and muscle metabolic economy (force/ATP) were measured in calf muscle using 31P MRS during isometric plantar flexion at 70 and 100% of maximum force, (HI) and (MI) respectively. Muscle fiber type and citrate synthase activity were determined in the lateral gastrocnemius. Significant inverse relationships (r from -0.28 to -0.74) were observed between oxidative metabolism measures and exercise economy (walking and muscle). Type IIa fiber distribution was inversely related to all measures of exercise economy (r from -0.51 to -0.64) and citrate synthase activity was inversely related to muscle metabolic economy at MI (r = -0.56). In addition, Type IIa fiber distribution and citrate synthase activity were positively related to VO2max and muscle OxPhos at HI and MI (r from 0.49 to 0.70). Type I fiber distribution was not related to any measure of exercise economy or oxidative capacity. Our results support the concept that exercise economy and oxidative capacity are inversely related. We have demonstrated this inverse relationship in women both by indirect calorimetry during walking and in muscle tissue by 31P MRS.

  1. A Muscle’s Force Depends on the Recruitment Patterns of Its Fibers

    PubMed Central

    Wakeling, James M.; Lee, Sabrina S. M.; Arnold, Allison S.; de Boef Miara, Maria; Biewener, Andrew A.

    2012-01-01

    Biomechanical models of whole muscles commonly used in simulations of musculoskeletal function and movement typically assume that the muscle generates force as a scaled-up muscle fiber. However, muscles are comprised of motor units that have different intrinsic properties and that can be activated at different times. This study tested whether a muscle model comprised of motor units that could be independently activated resulted in more accurate predictions of force than traditional Hill-type models. Forces predicted by the models were evaluated by direct comparison with the muscle forces measured in situ from the gastrocnemii in goats. The muscle was stimulated tetanically at a range of frequencies, muscle fiber strains were measured using sonomicrometry, and the activation patterns of the different types of motor unit were calculated from electromyographic recordings. Activation patterns were input into five different muscle models. Four models were traditional Hill-type models with different intrinsic speeds and fiber-type properties. The fifth model incorporated differential groups of fast and slow motor units. For all goats, muscles and stimulation frequencies the differential model resulted in the best predictions of muscle force. The in situ muscle output was shown to depend on the recruitment of different motor units within the muscle. PMID:22350666

  2. Increasing O-GlcNAcylation level on organ culture of soleus modulates the calcium activation parameters of muscle fibers.

    PubMed

    Cieniewski-Bernard, Caroline; Montel, Valerie; Berthoin, Serge; Bastide, Bruno

    2012-01-01

    O-N-acetylglucosaminylation is a reversible post-translational modification which presents a dynamic and highly regulated interplay with phosphorylation. New insights suggest that O-GlcNAcylation might be involved in striated muscle physiology, in particular in contractile properties such as the calcium activation parameters. By the inhibition of O-GlcNAcase, we investigated the effect of the increase of soleus O-GlcNAcylation level on the contractile properties by establishing T/pCa relationships. We increased the O-GlcNAcylation level on soleus biopsies performing an organ culture of soleus treated or not with PUGNAc or Thiamet-G, two O-GlcNAcase inhibitors. The enhancement of O-GlcNAcylation pattern was associated with an increase of calcium affinity on slow soleus skinned fibers. Analysis of the glycoproteins pattern showed that this effect is solely due to O-GlcNAcylation of proteins extracted from skinned biopsies. We also characterized the O-GlcNAcylated contractile proteins using a proteomic approach, and identified among others troponin T and I as being O-GlcNAc modified. We quantified the variation of O-GlcNAc level on all these identified proteins, and showed that several regulatory contractile proteins, predominantly fast isoforms, presented a drastic increase in their O-GlcNAc level. Since the only slow isoform of contractile protein presenting an increase of O-GlcNAc level was MLC2, the effect of enhanced O-GlcNAcylation pattern on calcium activation parameters could involve the O-GlcNAcylation of sMLC2, without excluding that an unidentified O-GlcNAc proteins, such as TnC, could be potentially involved in this mechanism. All these data strongly linked O-GlcNAcylation to the modulation of contractile activity of skeletal muscle.

  3. Abelson tyrosine-protein kinase 2 regulates myoblast proliferation and controls muscle fiber length

    PubMed Central

    Lee, Jennifer K; Hallock, Peter T

    2017-01-01

    Muscle fiber length is nearly uniform within a muscle but widely different among different muscles. We show that Abelson tyrosine-protein kinase 2 (Abl2) has a key role in regulating myofiber length, as a loss of Abl2 leads to excessively long myofibers in the diaphragm, intercostal and levator auris muscles but not limb muscles. Increased myofiber length is caused by enhanced myoblast proliferation, expanding the pool of myoblasts and leading to increased myoblast fusion. Abl2 acts in myoblasts, but as a consequence of expansion of the diaphragm muscle, the diaphragm central tendon is reduced in size, likely contributing to reduced stamina of Abl2 mutant mice. Ectopic muscle islands, each composed of myofibers of uniform length and orientation, form within the central tendon of Abl2+/− mice. Specialized tendon cells, resembling tendon cells at myotendinous junctions, form at the ends of these muscle islands, suggesting that myofibers induce differentiation of tendon cells, which reciprocally regulate myofiber length and orientation. PMID:29231808

  4. Abelson tyrosine-protein kinase 2 regulates myoblast proliferation and controls muscle fiber length.

    PubMed

    Lee, Jennifer K; Hallock, Peter T; Burden, Steven J

    2017-12-12

    Muscle fiber length is nearly uniform within a muscle but widely different among different muscles. We show that Abelson tyrosine-protein kinase 2 (Abl2) has a key role in regulating myofiber length, as a loss of Abl2 leads to excessively long myofibers in the diaphragm, intercostal and levator auris muscles but not limb muscles. Increased myofiber length is caused by enhanced myoblast proliferation, expanding the pool of myoblasts and leading to increased myoblast fusion. Abl2 acts in myoblasts, but as a consequence of expansion of the diaphragm muscle, the diaphragm central tendon is reduced in size, likely contributing to reduced stamina of Abl2 mutant mice. Ectopic muscle islands, each composed of myofibers of uniform length and orientation, form within the central tendon of Abl2 +/- mice. Specialized tendon cells, resembling tendon cells at myotendinous junctions, form at the ends of these muscle islands, suggesting that myofibers induce differentiation of tendon cells, which reciprocally regulate myofiber length and orientation.

  5. Rapid determination of myosin heavy chain expression in rat, mouse, and human skeletal muscle using multicolor immunofluorescence analysis.

    PubMed

    Bloemberg, Darin; Quadrilatero, Joe

    2012-01-01

    Skeletal muscle is a heterogeneous tissue comprised of fibers with different morphological, functional, and metabolic properties. Different muscles contain varying proportions of fiber types; therefore, accurate identification is important. A number of histochemical methods are used to determine muscle fiber type; however, these techniques have several disadvantages. Immunofluorescence analysis is a sensitive method that allows for simultaneous evaluation of multiple MHC isoforms on a large number of fibers on a single cross-section, and offers a more precise means of identifying fiber types. In this investigation we characterized pure and hybrid fiber type distribution in 10 rat and 10 mouse skeletal muscles, as well as human vastus lateralis (VL) using multicolor immunofluorescence analysis. In addition, we determined fiber type-specific cross-sectional area (CSA), succinate dehydrogenase (SDH) activity, and α-glycerophosphate dehydrogenase (GPD) activity. Using this procedure we were able to easily identify pure and hybrid fiber populations in rat, mouse, and human muscle. Hybrid fibers were identified in all species and made up a significant portion of the total population in some rat and mouse muscles. For example, rat mixed gastrocnemius (MG) contained 12.2% hybrid fibers whereas mouse white tibialis anterior (WTA) contained 12.1% hybrid fibers. Collectively, we outline a simple and time-efficient method for determining MHC expression in skeletal muscle of multiple species. In addition, we provide a useful resource of the pure and hybrid fiber type distribution, fiber CSA, and relative fiber type-specific SDH and GPD activity in a number of rat and mouse muscles.

  6. Slowed Relaxation in Fatigued Skeletal Muscle Fibers of Xenopus and Mouse

    PubMed Central

    Westerblad, Håkan; Lännergren, Jan; Allen, David G.

    1997-01-01

    Slowing of relaxation is an important characteristic of skeletal muscle fatigue. The aim of the present study was to quantify the relative contribution of altered Ca2+ handling (calcium component) and factors down-stream to Ca2+ (cross-bridge component) to the slowing of relaxation in fatigued fibers of Xenopus and mouse. Two types of Xenopus fibers were used: easily fatigued, type 1 fibers and fatigue resistant, type 2 fibers. In these Xenopus fibers the free myoplasmic [Ca2+] ([Ca2+]i) was measured with indo-1, and the relaxation of Ca2+-derived force, constructed from tetanic [Ca2+]i records and in vivo [Ca2+]i-force curves, was analyzed. An alternative method was used in both Xenopus and mouse fibers: fibers were rapidly shortened during the initial phase of relaxation, and the time to the peak of force redevelopment was measured. These two methods gave similar results and showed proportional slowing of the calcium and cross-bridge components of relaxation in both fatigued type 1 and type 2 Xenopus fibers, whereas only the cross-bridge component was slowed in fatigued mouse fibers. Ca2+ removal from the myoplasm during relaxation was markedly less effective in Xenopus fibers as compared to mouse fibers. Fatigued Xenopus fibers displayed a reduced rate of sarcoplasmic reticulum Ca2+ uptake and increased sarcoplasmic reticulum Ca2+ leak. Some fibers were stretched at various times during relaxation. The resistance to these stretches was increased during fatigue, especially in Xenopus fibers, which indicates that longitudinal movements during relaxation had become less pronounced and this might contribute to the increased cross-bridge component of relaxation in fatigue. In conclusion, slowing of relaxation in fatigued Xenopus fibers is caused by impaired Ca2+ handling and altered cross-bridge kinetics, whereas the slowing in mouse fibers is only due to altered cross-bridge kinetics. PMID:9089444

  7. Velocity and attenuation of shear waves in the phantom of a muscle-soft tissue matrix with embedded stretched fibers

    NASA Astrophysics Data System (ADS)

    Rudenko, O. V.; Tsyuryupa, S. N.; Sarvazyan, A. P.

    2016-09-01

    We develop a theory of the elasticity moduli and dissipative properties of a composite material: a phantom simulating muscle tissue anisotropy. The model used in the experiments was made of a waterlike polymer with embedded elastic filaments imitating muscle fiber. In contrast to the earlier developed phenomenological theory of the anisotropic properties of muscle tissue, here we obtain the relationship of the moduli with characteristic sizes and moduli making up the composite. We introduce the effective elasticity moduli and viscosity tensor components, which depend on stretching of the fibers. We measure the propagation velocity of shear waves and the shear viscosity of the model for regulated tension. Waves were excited by pulsed radiation pressure generated by modulated focused ultrasound. We show that with increased stretching of fibers imitating muscle contraction, an increase in both elasticity and viscosity takes place, and this effect depends on the wave propagation direction. The results of theoretical and experimental studies support our hypothesis on the protective function of stretched skeletal muscle, which protects bones and joints from trauma.

  8. Activation of respiratory muscles during respiratory muscle training.

    PubMed

    Walterspacher, Stephan; Pietsch, Fabian; Walker, David Johannes; Röcker, Kai; Kabitz, Hans-Joachim

    2018-01-01

    It is unknown which respiratory muscles are mainly activated by respiratory muscle training. This study evaluated Inspiratory Pressure Threshold Loading (IPTL), Inspiratory Flow Resistive Loading (IFRL) and Voluntary Isocapnic Hyperpnea (VIH) with regard to electromyographic (EMG) activation of the sternocleidomastoid muscle (SCM), parasternal muscles (PARA) and the diaphragm (DIA) in randomized order. Surface EMG were analyzed at the end of each training session and normalized using the peak EMG recorded during maximum inspiratory maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion pressure: PImax). 41 healthy participants were included. Maximal activation was achieved for SCM by SnPna; the PImax activated predominantly PARA and DIA. Activations of SCM and PARA were higher in IPTL and VIH than for IFRL (p<0.05). DIA was higher applying IPTL compared to IFRL or VIH (p<0.05). IPTL, IFRL and VIH differ in activation of inspiratory respiratory muscles. Whereas all methods mainly stimulate accessory respiratory muscles, diaphragm activation was predominant in IPTL. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. How does the nucleolar number involve in muscle fiber atrophy? Response to Beta-guanidinopropionic acid supplementation

    NASA Astrophysics Data System (ADS)

    Matsuoka, Yoshikazu; Kawano, Fuminori; Oke, Yoshihiko; Higo, Yoko; Umemoto, Shiori; Kawabe, Naoko; Wang, Xiaodong; Terada, Masahiro; Shinoda, Yo; Lan, Yongbo; Ogura, Akihiko; Ohira, Yoshinobu

    2005-08-01

    To investigate the relationship between the myonuclear capability and the number of nucleolus during muscle remodeling, oral supplementation of β-guanidinopropionic acid (β-GPA) on the characteristics of plantaris muscle fibers was performed for 2 weeks in adult male Wistar rats. Effects of β-GPA supply in culture medium on mouse myoblast cell line C2C12 was also studied. The mean fiber cross-sectional area was less in β-GPA-fed than control rats (35%, p<0.05). And the myonuclear number per mm of fiber length was significantly greater (35%, p<0.05). Thus, the cytoplasmic volume per myonucleus was less (52%) in β-GPA-fed rats (p<0.05). The number of nucleolar organizer regions (NORs) per myonucleus was also less (17%) in β-GPA-fed group (p<0.05). The number of NORs was greater (14%) in the myoblasts cultured with creatine phosphate compared with non-supplemented control, but it was less (10%) in the myoblasts cultured with β-GPA (p<0.05). Further, the number of NORs was also greater (26%) in the differentiated myotubes cultured with creatine phosphate (p<0.05). The results suggested that the nucleoli may play some role(s) in the regulation of muscle fiber size and its number may be influenced by creatine content.

  10. Differential effects of peroxynitrite on contractile protein properties in fast- and slow-twitch skeletal muscle fibers of rat.

    PubMed

    Dutka, T L; Mollica, J P; Lamb, G D

    2011-03-01

    Oxidative modification of contractile proteins is thought to be a key factor in muscle weakness observed in many pathophysiological conditions. In particular, peroxynitrite (ONOO(-)), a potent short-lived oxidant, is a likely candidate responsible for this contractile dysfunction. In this study ONOO(-) or 3-morpholinosydnonimine (Sin-1, a ONOO(-) donor) was applied to rat skinned muscle fibers to characterize the effects on contractile properties. Both ONOO(-) and Sin-1 exposure markedly reduced maximum force in slow-twitch fibers but had much less effect in fast-twitch fibers. The rate of isometric force development was also reduced without change in the number of active cross bridges. Sin-1 exposure caused a disproportionately large decrease in Ca(2+) sensitivity, evidently due to coproduction of superoxide, as it was prevented by Tempol, a superoxide dismutase mimetic. The decline in maximum force with Sin-1 and ONOO(-) treatments could be partially reversed by DTT, provided it was applied before the fiber was activated. Reversal by DTT indicates that the decrease in maximum force was due at least in part to oxidation of cysteine residues. Ascorbate caused similar reversal, further suggesting that the cysteine residues had undergone S-nitrosylation. The reduction in Ca(2+) sensitivity, however, was not reversed by either DTT or ascorbate. Western blot analysis showed cross-linking of myosin heavy chain (MHC) I, appearing as larger protein complexes after ONOO(-) exposure. The findings suggest that ONOO(-) initially decreases maximum force primarily by oxidation of cysteine residues on the myosin heads, and that the accompanying decrease in Ca(2+) sensitivity is likely due to other, less reversible actions of hydroxyl or related radicals.

  11. Nerve-muscle interactions during flight muscle development in Drosophila

    NASA Technical Reports Server (NTRS)

    Fernandes, J. J.; Keshishian, H.

    1998-01-01

    During Drosophila pupal metamorphosis, the motoneurons and muscles differentiate synchronously, providing an opportunity for extensive intercellular regulation during synapse formation. We examined the existence of such interactions by developmentally delaying or permanently eliminating synaptic partners during the formation of indirect flight muscles. When we experimentally delayed muscle development, we found that although adult-specific primary motoneuron branching still occurred, the higher order (synaptic) branching was suspended until the delayed muscle fibers reached a favourable developmental state. In reciprocal experiments we found that denervation caused a decrease in the myoblast pool. Furthermore, the formation of certain muscle fibers (dorsoventral muscles) was specifically blocked. Exceptions were the adult muscles that use larval muscle fibers as myoblast fusion targets (dorsal longitudinal muscles). However, when these muscles were experimentally compelled to develop without their larval precursors, they showed an absolute dependence on the motoneurons for their formation. These data show that the size of the myoblast pool and early events in fiber formation depend on the presence of the nerve, and that, conversely, peripheral arbor development and synaptogenesis is closely synchronized with the developmental state of the muscle.

  12. Non-weight bearing-induced muscle weakness: the role of myosin quantity and quality in MHC type II fibers.

    PubMed

    Kim, Jong-Hee; Thompson, LaDora V

    2014-07-15

    We tested the hypothesis that non-weight bearing-induced muscle weakness (i.e., specific force) results from decreases in myosin protein quantity (i.e., myosin content per half-sarcomere and the ratio of myosin to actin) and quality (i.e., force per half-sarcomere and population of myosin heads in the strong-binding state during muscle contraction) in single myosin heavy chain (MHC) type II fibers. Fisher-344 rats were assigned to weight-bearing control (Con) or non-weight bearing (NWB). The NWB rats were hindlimb unloaded for 2 wk. Diameter, force, and MHC content were determined in permeabilized single fibers from the semimembranosus muscle. MHC isoform and the ratio of MHC to actin in each fiber were determined by gel electrophoresis and silver staining techniques. The structural distribution of myosin from spin-labeled fiber bundles during maximal isometric contraction was evaluated using electron paramagnetic resonance spectroscopy. Specific force (peak force per cross-sectional area) in MHC type IIB and IIXB fibers from NWB was significantly reduced by 38% and 18%, respectively. MHC content per half-sarcomere was significantly reduced by 21%. Two weeks of hindlimb unloading resulted in a reduced force per half-sarcomere of 52% and fraction of myosin strong-binding during contraction of 34%. The results suggest that reduced myosin and actin content (quantity) and myosin quality concomitantly contribute to non-weight bearing-related muscle weakness. Copyright © 2014 the American Physiological Society.

  13. Functional pools of oxidative and glycolytic fibers in human muscle observed by 31P magnetic resonance spectroscopy during exercise.

    PubMed Central

    Park, J H; Brown, R L; Park, C R; McCully, K; Cohn, M; Haselgrove, J; Chance, B

    1987-01-01

    Quantitative probing of heterogeneous regions in muscle is feasible with phosphorus-31 magnetic resonance spectroscopy because of the differentiation of metabolic patterns of glycolytic and oxidative fibers. A differential recruitment of oxidative and glycolytic fibers during exercise was demonstrated in 4 of 10 untrained young men by following changes in phosphate metabolites. Concentrations of inorganic phosphate (Pi), phosphocreatine, and ATP were estimated in the wrist flexor muscles of the forearm at rest, during two cycles of three grades of exercise, and in recovery. At high work levels (40% of maximum strength), two distinct Pi peaks were observed and identified with Pi pools at pH 6.9 and pH 5.9-6.4, respectively. These could be accounted for as follows. At the lowest level of work (using 20% of maximum strength), early recruitment primarily of oxidative (type I) and possibly some intermediate (type IIA) muscle fibers occurs with relatively little net lactate production and consequently little decrease in pH. At higher work loads, however, primarily glycolytic (type IIB) muscle fibers are recruited, which have relatively high net lactate production and therefore generate a second pool of Pi at low pH. ATP depletion (35-54%) and Pi losses accompanied the reduction in ability to perform during the first exercise cycle. When the cycle of graded exercise was repeated immediately, the total Pi remained high but gave rise to only one peak at pH 6.8-7.0. These observations indicated exhaustion of glycolytic type IIB fibers, removal of lactate by high local blood flow, and sustained contractions largely by oxidative type I and IIA fibers. A functional differentiation of fiber types could also be demonstrated during recovery if exercise was stopped while two pools of Pi were still apparent. In the first 3 min of recovery, the Pi peak at pH 6.8-6.9 disappeared almost entirely, whereas the Pi peak at pH 6.0 remained unaltered, reflecting the faster recovery of

  14. Ontogeny of muscle bioenergetics in Adelie penguin chicks (Pygoscelis adeliae).

    PubMed

    Fongy, Anaïs; Romestaing, Caroline; Blanc, Coralie; Lacoste-Garanger, Nicolas; Rouanet, Jean-Louis; Raccurt, Mireille; Duchamp, Claude

    2013-11-01

    The ontogeny of pectoralis muscle bioenergetics was studied in growing Adélie penguin chicks during the first month after hatching and compared with adults using permeabilized fibers and isolated mitochondria. With pyruvate-malate-succinate or palmitoyl-carnitine as substrates, permeabilized fiber respiration markedly increased during chick growth (3-fold) and further rose in adults (1.4-fold). Several markers of muscle fiber oxidative activity (cytochrome oxidase, citrate synthase, hydroxyl-acyl-CoA dehydrogenase) increased 6- to 19-fold with age together with large rises in intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondrial content (3- to 5-fold) and oxidative activities (1.5- to 2.4-fold). The proportion of IMF relative to SS mitochondria increased with chick age but markedly dropped in adults. Differences in oxidative activity between mitochondrial fractions were reduced in adults compared with hatched chicks. Extrapolation of mitochondrial to muscle respirations revealed similar figures with isolated mitochondria and permeabilized fibers with carbohydrate-derived but not with lipid-derived substrates, suggesting diffusion limitations of lipid substrates with permeabilized fibers. Two immunoreactive fusion proteins, mitofusin 2 (Mfn2) and optic atrophy 1 (OPA1), were detected by Western blots on mitochondrial extracts and their relative abundance increased with age. Muscle fiber respiration was positively related with Mfn2 and OPA1 relative abundance. Present data showed by two complementary techniques large ontogenic increases in muscle oxidative activity that may enable birds to face thermal emancipation and growth in childhood and marine life in adulthood. The concomitant rise in mitochondrial fusion protein abundance suggests a role of mitochondrial networks in the skeletal muscle processes of bioenergetics that enable penguins to overcome harsh environmental constraints.

  15. Thyroid hormone stimulates myoglobin expression in soleus and extensorum digitalis longus muscles of rats: concomitant alterations in the activities of Krebs cycle oxidative enzymes.

    PubMed

    dos Santos, R A; Giannocco, G; Nunes, M T

    2001-06-01

    Myoglobin (Mb) gene expression, Citrate Synthase (CS) and Succinate Dehydrogenase (SDH) activities of Soleus (S) and Extensorum Digitalis Longus (EDL) muscles were studied in intact, thyroidectomized and T3-treated (25 microg/100g, BW, ip, 15 days) rats. The fiber type composition of S muscle was also evaluated and used as control of the T3-induced effects. In the S muscle, the T3 treatment increased the Mb mRNA and protein expression, as well as the CS and SDH activity. These changes occurred parallel to the expected increase in type II (fast) and decrease in type I (slow)-fibers in S muscle. In the hypothyroid state, the Mb mRNA was decreased, while the Mb expression and CS activity tended to decrease. In contrast the SDH activity was increased, probably due to the enhanced motor activity that occurs as a short-term response to the hypothermia induced by hypothyroidism. In the EDL, the alterations were milder than those in S muscle in both thyroid states. These findings show that Mb gene expression is induced by T3. This is concomitant with the enhancement of Krebs Cycle enzyme activities and provides additional evidence that thyroid hormone increases the aerobic potential of skeletal muscles, as well as the speed of muscle contraction.

  16. Trunk extensor muscle fatigue influences trunk muscle activities.

    PubMed

    Hoseinpoor, Tahere Seyed; Kahrizi, Sedighe; Mobini, Bahram

    2015-01-01

    Trunk muscles fatigue is one of the risk factors in workplaces and daily activities. Loads would be redistributed among active and passive tissues in a non-optimal manner in fatigue conditions. Therefore, a single tissue might be overloaded with minimal loads and as a result the risk of injury would increase. The goal of this paper was to assess the electromyographic response of trunk extensor and abdominal muscles after trunk extensor muscles fatigue induced by cyclic lifting task. This was an experimental study that twenty healthy women participated. For assessing automatic response of trunk extensor and abdominal muscles before and after the fatigue task, electromyographic activities of 6 muscles: thorasic erector spine (TES), lumbar erector spine (LES), lumbar multifidus (LMF), transverse abdominis/ internal oblique (TrA/IO), rectus abdominis (RA) and external oblique (EO) were recorded in standing position with no load and symmetric axial loads equal to 25% of their body weights. Statistical analysis showed that all the abdominal muscles activity decreased with axial loads after performing fatigue task but trunk extensor activity remained constant. Results of the current study indicated that muscle recruitment strategies changed with muscle fatigue and load bearing, therefore risks of tissue injury may increase in fatigue conditions.

  17. An introductory biology lab that uses enzyme histochemistry to teach students about skeletal muscle fiber types.

    PubMed

    Sweeney, Lauren J; Brodfuehrer, Peter D; Raughley, Beth L

    2004-12-01

    One important goal of introductory biology laboratory experiences is to engage students directly in all steps in the process of scientific discovery. Even when laboratory experiences are built on principles discussed in the classroom, students often do not adequately apply this background to interpretation of results they obtain in lab. This disconnect has been described at the level of medical education (4), so it should not be surprising that educators have struggled with this same phenomenon at the undergraduate level. We describe a new introductory biology lab that challenges students to make these connections. The lab utilizes enzyme histochemistry and morphological observations to draw conclusions about the composition of functionally different types of muscle fibers present in skeletal muscle. We report that students were not only successful at making these observations on a specific skeletal muscle, the gastrocnemius of the frog Rana pipiens, but that they were able to connect their results to the principles of fiber type differences that exist in skeletal muscles in all vertebrates.

  18. Regional differences in hyoid muscle activity and length-dynamics during mammalian head-shaking

    PubMed Central

    Wentzel, Sarah E.; Konow, Nicolai; German, Rebecca Z.

    2010-01-01

    The sternohyoid (SH) and geniohyoid (GH) are antagonist strap-muscles that are active during a number of different behaviors, including sucking, intraoral transport, swallowing, breathing, and extension/flexion of the neck. Because these muscles have served different functions through the evolutionary history of vertebrates, it is quite likely they will have complex patterns of electrical activity and muscle fiber contraction. Different regions of the sternohyoid exhibit different contraction and activity patterns during a swallow. We examined the dynamics of the sternohyoid and geniohyoid muscles during an unrestrained, and vigorous head-shake behavior in an animal model of human head, neck and hyolingual movement. A gentle touch to infant pig ears elicited a head shake of several head revolutions. Using sonomicrometry and intramuscular EMG we measured regional (within) muscle strain and activity in SH and GH. We found that EMG was consistent across three regions (anterior, belly and posterior) of each muscle. Changes in muscle length however, were more complex. In the SH, mid-belly length-change occurred out of phase with the anterior and posterior end-regions, but with a zero-lag timing; the anterior region shortened prior to the posterior. In the GH, the anterior region shortened prior to, and out of phase with the mid-belly and posterior regions. Head-shaking is a relatively simple reflex behavior, yet the underlying patterns of muscle length-dynamics and EMG activity are not. The regional complexity in SH and GH, similar to regionalization of SH during swallowing, suggests that these ‘simple hyoid strap muscles’ are more complex than textbooks often suggest. PMID:21370479

  19. Design and testing of regulatory cassettes for optimal activity in skeletal and cardiac muscles.

    PubMed

    Himeda, Charis L; Chen, Xiaolan; Hauschka, Stephen D

    2011-01-01

    Gene therapy for muscular dystrophies requires efficient gene delivery to the striated musculature and specific, high-level expression of the therapeutic gene in a physiologically diverse array of muscles. This can be achieved by the use of recombinant adeno-associated virus vectors in conjunction with muscle-specific regulatory cassettes. We have constructed several generations of regulatory cassettes based on the enhancer and promoter of the muscle creatine kinase gene, some of which include heterologous enhancers and individual elements from other muscle genes. Since the relative importance of many control elements varies among different anatomical muscles, we are aiming to tailor these cassettes for high-level expression in cardiac muscle, and in fast and slow skeletal muscles. With the achievement of efficient intravascular gene delivery to isolated limbs, selected muscle groups, and heart in large animal models, the design of cassettes optimized for activity in different muscle types is now a practical goal. In this protocol, we outline the key steps involved in the design of regulatory cassettes for optimal activity in skeletal and cardiac muscle, and testing in mature muscle fiber cultures. The basic principles described here can also be applied to engineering tissue-specific regulatory cassettes for other cell types.

  20. Myogenin, MyoD and IGF-I regulate muscle mass but not fiber-type conversion during resistance training in rats.

    PubMed

    Aguiar, A F; Vechetti-Júnior, I J; Alves de Souza, R W; Castan, E P; Milanezi-Aguiar, R C; Padovani, C R; Carvalho, R F; Silva, M D P

    2013-04-01

    The purpose of this study was to test the hypothesis that skeletal muscle adaptations induced by long-term resistance training (RT) are associated with increased myogenic regulatory factors (MRF) and insulin-like growth factor-I (IGF-I) mRNA expression in rats skeletal muscle. Male Wistar rats were divided into 4 groups: 8-week control (C8), 8-week trained (T8), 12-week control (C12) and 12-week trained (T12). Trained rats were submitted to a progressive RT program (4 sets of 10-12 repetitions at 65-75% of the 1RM, 3 day/week), using a squat-training apparatus with electric stimulation. Muscle hypertrophy was determined by measurement of muscle fiber cross-sectional area (CSA) of the muscle fibers, and myogenin, MyoD and IGF-I mRNA expression were measured by RT-qPCR. A hypertrophic stabilization occurred between 8 and 12 weeks of RT (control-relative % area increase, T8: 29% vs. T12: 35%; p>0.05) and was accompanied by the stabilization of myogenin (control-relative % increase, T8: 44.8% vs. T12: 37.7%, p>0.05) and MyoD (control-relative % increase, T8: 22.9% vs. T12: 22.3%, p>0.05) mRNA expression and the return of IGF-I mRNA levels to the baseline (control-relative % increase, T8: 30.1% vs. T12: 1.5%, p<0.05). Moreover, there were significant positive correlations between the muscle fiber CSA and mRNA expression for MyoD (r=0.85, p=0.0001), myogenin (r=0.87, p=0.0001), and IGF-I (r=0.88, p=0.0001). The significant (p<0.05) increase in myogenin, MyoD and IGF-I mRNA expression after 8 weeks was not associated with changes in the fiber-type frequency. In addition, there was a type IIX/D-to-IIA fiber conversion at 12 weeks, even with the stabilization of MyoD and myogenin expression and the return of IGF-I levels to baseline. These results indicate a possible interaction between MRFs and IGF-I in the control of muscle hypertrophy during long-term RT and suggest that these factors are involved more in the regulation of muscle mass than in fiber-type conversion.

  1. The Effects of Ligustrazine on the Ca2+ Concentration of Soleus and Gastrocnemius Muscle Fibers in Hindlimb Unloaded Rat

    NASA Astrophysics Data System (ADS)

    Gao, Yunfang; Goswami, Nandu; Du, Bei; Hu, Huanxin; Wu, Xue

    Background Spaceflight or inactivity (bed rest, limb immobilization, hindlimb unloading) causes skeletal muscle atrophy. Recent studies show that an increase in protein degradation is an important mechanism for disuse atrophy. Furthermore, the calcium overload of disuse-atrophied muscle fiber has been shown to initiate the skeletal muscle proteolysis in disuse atrophy. Ligustrazine (tetramethylpyrazine, TMP), one of the important active ingredient extracted from Chuanxiong, has been shown by our group to increase muscle fiber cross-sectional area in atrophied soleus induced by 14 days hindlimb unloading. However, the underlying mechanisms of ligustrazine effects on disuse-atrophied muscle fibers remain unknown. Objective: We investigated the effects of ligustrazine on the cytoplasmic calcium overloading in soleus and gastrocnemius in 14 days hindlimb unloaded (HU) rats. Methods: Adult female Sprague-Dawley rats were matched for body mass and randomly assigned to three groups (n=8, each group): 1) synchronous control (CON); HU + intragastric water instillation (HU+W); HU + intragastric 60.0 mg kg-1 ligustrazine instillation (HU+Tmp). Laser scanning confocal microscope assessed the concentrations of cytoplasmic calcium ions. Spaceflight disuse atrophy was simulated by hindlimb unloading, provided by tail suspension. Results: 1) Compared with CON, the concentration of soleus intracellular calcium ion in HU+W and HU+Tmp increased 330% and 86% respectively P<0.01). Compared with HU+W, the concentration of soleus intracellular calcium ion in HU+Tmp decreased by 130% P<0.01). 2) Compared with CON, the concentration of gastrocnemius intracellular calcium ion in HU+W and HU+Tmp increased 189.8% and 32.1% respectively P<0.01). Compared with HU+W, the concentration of gastrocnemius intracellular calcium ion in HU+Tmp decreased by 119.3% (P<0.01). Conclusion: After 14 days of hindlimb unloading, cytoplasmic calcium of soleus (slow-twitch muscle) and gastrocnemius (fast

  2. Dietary Correlates of Primate Masticatory Muscle Fiber Architecture.

    PubMed

    Hartstone-Rose, Adam; Deutsch, Ashley R; Leischner, Carissa L; Pastor, Francisco

    2018-02-01

    Analyses of masticatory muscle architecture-specifically fascicle length (FL; a correlate of muscle stretch and contraction speed) and physiological cross-sectional area (PCSA; a correlate of force)-reveal soft-tissue dietary adaptations. For instance, consumers of large, soft foods are expected to have relatively long FL, while consumers of obdurate foods are expected to have relatively high PCSA. Unfortunately, only a few studies have analyzed these variables across large primate samples-an order of particular interest because it is our own. Previous studies found that, in strepsirrhines, force variables (PCSA and muscle masses; MM) scale with isometry or slight positive allometry, while the body size corrected FL residuals correlate with food sizes. However, a study of platyrrhines using different methods (in which the authors physically cut muscles between fascicles) found very different trends: negative allometry for both the stretch and force variables. Here, we apply the methods used in the strepsirrhine study (chemical dissection of fascicles to ensure full length measurements) to reevaluate these trends in platyrrhines and extend this research to include catarrhines. Our results conform to the previous strepsirrhine trends: there is no evidence of negative allometry in platyrrhines. Rather, in primates broadly and catarrhines specifically, MM and PCSA scale with isometry or positive allometry. When examining size-adjusted variables, it is clear that fascicle lengths (especially those of the temporalis muscle) correlate with diet: species that consume soft, larger, foods have longer masticatory fiber lengths which would allow them to open their jaws to wider gape angles. Anat Rec, 301:311-324, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  3. Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

    NASA Technical Reports Server (NTRS)

    Baldwin, K. M.; Haddad, F.

    2001-01-01

    The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T(3), 3,5,3'-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T(3)/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the beta-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T(3) or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T(3) and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of

  4. Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy.

    PubMed

    Petchey, Louisa K; Risebro, Catherine A; Vieira, Joaquim M; Roberts, Tom; Bryson, John B; Greensmith, Linda; Lythgoe, Mark F; Riley, Paul R

    2014-07-01

    Correct regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-related homeobox factor 1 (Prox1) during mouse heart development in the direct transcriptional repression of the fast-twitch skeletal muscle genes troponin T3, troponin I2, and myosin light chain 1. A proportion of cardiac-specific Prox1 knockout mice survive beyond birth with hearts characterized by marked overexpression of fast-twitch genes and postnatal development of a fatal dilated cardiomyopathy. Through conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved requirement for Prox1 in the repression of troponin T3, troponin I2, and myosin light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1 ablation as sufficient to cause a switch from a slow- to fast-twitch muscle phenotype. Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease.

  5. Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

    PubMed Central

    Petchey, Louisa K.; Risebro, Catherine A.; Vieira, Joaquim M.; Roberts, Tom; Bryson, John B.; Greensmith, Linda; Lythgoe, Mark F.; Riley, Paul R.

    2014-01-01

    Correct regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-related homeobox factor 1 (Prox1) during mouse heart development in the direct transcriptional repression of the fast-twitch skeletal muscle genes troponin T3, troponin I2, and myosin light chain 1. A proportion of cardiac-specific Prox1 knockout mice survive beyond birth with hearts characterized by marked overexpression of fast-twitch genes and postnatal development of a fatal dilated cardiomyopathy. Through conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved requirement for Prox1 in the repression of troponin T3, troponin I2, and myosin light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1 ablation as sufficient to cause a switch from a slow- to fast-twitch muscle phenotype. Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease. PMID:24938781

  6. Stiffness and fraction of Myosin motors responsible for active force in permeabilized muscle fibers from rabbit psoas.

    PubMed

    Linari, Marco; Caremani, Marco; Piperio, Claudia; Brandt, Philip; Lombardi, Vincenzo

    2007-04-01

    The stiffness of the single myosin motor (epsilon) is determined in skinned fibers from rabbit psoas muscle by both mechanical and thermodynamic approaches. Changes in the elastic strain of the half-sarcomere (hs) are measured by fast mechanics both in rigor, when all myosin heads are attached, and during active contraction, with the isometric force (T0) modulated by changing either [Ca2+] or temperature. The hs compliance is 43.0+/-0.8 nm MPa-1 in isometric contraction at saturating [Ca2+], whereas in rigor it is 28.2+/-1.1 nm MPa-1. The equivalent compliance of myofilaments is 21.0+/-3.3 nm MPa-1. Accordingly, the stiffness of the ensemble of myosin heads attached in the hs is 45.5+/-1.7 kPa nm-1 in isometric contraction at saturating [Ca2+] (e0), and in rigor (er) it rises to 138.9+/-21.2 kPa nm-1. Epsilon, calculated from er and the lattice molecular dimensions, is 1.21+/-0.18 pN nm-1. epsilon estimated, using a thermodynamic approach, from the relation of T0 at saturating [Ca2+] versus the reciprocal of absolute temperature is 1.25+/-0.14 pN nm-1, similar to that estimated for fibers in rigor. Consequently, the ratio e0/er (0.33+/-0.05) can be used to estimate the fraction of attached heads during isometric contraction at saturating [Ca2+]. If the osmotic agent dextran T-500 (4 g/100 ml) is used to reduce the lateral filament spacing of the relaxed fiber to the value before skinning, both e0 and er increase by approximately 40%. Epsilon becomes approximately 1.7 pN nm-1 and the fraction and the force of myosin heads attached in the isometric contraction remain the same as before dextran application. The finding that the fraction of myosin heads attached to actin in an isometric contraction is 0.33 rules out the hypothesis of multiple mechanical cycles per ATP hydrolyzed.

  7. Adaptation of rat soleus muscles to 4 wk of intermittent strain

    NASA Technical Reports Server (NTRS)

    Stauber, W. T.; Miller, G. R.; Grimmett, J. G.; Knack, K. K.

    1994-01-01

    The effect of repeated strains on rat soleus muscles was investigated by stretching active muscles 3 times/wk for 4 wk with two different methods of stretching. The adaptation of myofibers and noncontractile tissue was followed by histochemical techniques and computer-assisted image analysis. Muscle hypertrophy was seen in the slow-stretched muscles, which increased in mass by 13% and increased in myofiber cross-sectional area by 30%. In the fast-stretched muscle, mass increased by 10% but myofiber cross-sectional area actually decreased. This decrease in mean fiber area was the result of a population of very small fibers (population A) that coexisted with slightly smaller normal-sized fibers (population B). Fibers in population A did not have the distribution expected from atrophy compared with atrophic fibers from unloaded muscles; they were much smaller. In addition, there was a 44% increase in noncontractile tissue in the fast-stretched muscles. Thus, soleus muscles subjected to repeated strains respond differently to slow and fast stretching. Slow stretching results in typical muscle hypertrophy, whereas fast stretching produces somewhat larger muscles but with a mixture of small and normal-sized myofibers accompanied by a marked proliferation of noncontractile tissue.

  8. Agonist muscle adaptation accompanied by antagonist muscle atrophy in the hindlimb of mice following stretch-shortening contraction training.

    PubMed

    Rader, Erik P; Naimo, Marshall A; Ensey, James; Baker, Brent A

    2017-02-02

    The vast majority of dynamometer-based animal models for investigation of the response to chronic muscle contraction exposure has been limited to analysis of isometric, lengthening, or shortening contractions in isolation. An exception to this has been the utilization of a rat model to study stretch-shortening contractions (SSCs), a sequence of consecutive isometric, lengthening, and shortening contractions common during daily activity and resistance-type exercise. However, the availability of diverse genetic strains of rats is limited. Therefore, the purpose of the present study was to develop a dynamometer-based SSC training protocol to induce increased muscle mass and performance in plantarflexor muscles of mice. Young (3 months old) C57BL/6 mice were subjected to 1 month of plantarflexion SSC training. Hindlimb muscles were analyzed for muscle mass, quantitative morphology, myogenesis/myopathy relevant gene expression, and fiber type distribution. The main aim of the research was achieved when training induced a 2-fold increase in plantarflexion peak torque output and a 19% increase in muscle mass for the agonist plantaris (PLT) muscle. In establishing this model, several outcomes emerged which raised the value of the model past that of being a mere recapitulation of the rat model. An increase in the number of muscle fibers per transverse muscle section accounted for the PLT muscle mass gain while the antagonist tibialis anterior (TA) muscle atrophied by 30% with preferential atrophy of type IIb and IIx fibers. These alterations were accompanied by distinct gene expression profiles. The findings confirm the development of a stretch-shortening contraction training model for the PLT muscle of mice and demonstrate that increased cross-sectional fiber number can occur following high-intensity SSC training. Furthermore, the TA muscle atrophy provides direct evidence for the concept of muscle imbalance in phasic non-weight bearing muscles, a concept largely

  9. In Vivo Rodent Models of Skeletal Muscle Adaptation to Decreased Use.

    PubMed

    Cho, Su Han; Kim, Jang Hoe; Song, Wook

    2016-03-01

    Skeletal muscle possesses plasticity and adaptability to external and internal physiological changes. Due to these characteristics, skeletal muscle shows dramatic changes depending on its response to stimuli such as physical activity, nutritional changes, disease status, and environmental changes. Modulation of the rate of protein synthesis/degradation plays an important role in atrophic responses. The purpose of this review is to describe different features of skeletal muscle adaptation with various models of deceased use. In this review, four models were addressed: immobilization, spinal cord transection, hindlimb unloading, and aging. Immobilization is a form of decreased use in which skeletal muscle shows electrical activity, tension development, and motion. These results differ by muscle group. Spinal cord transection was selected to simulate spinal cord injury. Similar to the immobilization model, dramatic atrophy occurs in addition to fiber type conversion in this model. Despite the fact that electromyography shows unremarkable changes in muscle after hindlimb unloading, decreased muscle mass and contractile force are observed. Lastly, aging significantly decreases the numbers of muscle fibers and motor units. Skeletal muscle responses to decreased use include decreased strength, decreased fiber numbers, and fiber type transformation. These four models demonstrated different changes in the skeletal muscle. This review elucidates the different skeletal muscle adaptations in these four decreased use animal models and encourages further studies.

  10. [Changes in cell respiration of postural muscle fibers under long-term gravitational unloading after dietary succinate supplementation].

    PubMed

    Ogneva, I V; Veselova, O M; Larina, I M

    2011-01-01

    The intensity of cell respiration of the rat m. soleus, m. gastrocnemius c.m. and tibialis anterior fibers during 35-day gravitational unloading, with the addition of succinate in the diet at a dosage rate of 50 mg per 1 kg animal weight has been investigated. The gravitational unloading was modeled by antiorthostatic hindlimb suspension. The intensity of cell respiration was estimated by polarography. It was shown that the rate of oxygen consumption by soleus and gastrocnemius fibers on endogenous and exogenous substrates and with the addition of ADP decreases after the discharge. This may be associated with the transition to the glycolytic energy path due to a decrease in the EMG-activity. At the same time, the respiration rate after the addition of exogenous substrates in soleus fibers did not increase, indicating a disturbance in the function of the NCCR-section of the respiratory chain and more pronounced changes in the structure of muscle fibers. In tibialis anterior fibers, no changes in oxygen consumption velocity were observed. The introduction of succinate to the diet of rats makes it possible to prevent the negative effects of hypokinesia, although it reduces the basal level of intensity of cell respiration.

  11. Differential Effects of Sepsis and Chronic Inflammation on Diaphragm Muscle Fiber Type, Thyroid Hormone Metabolism, and Mitochondrial Function.

    PubMed

    Bloise, Flavia F; van der Spek, Anne H; Surovtseva, Olga V; Ortiga-Carvalho, Tania Maria; Fliers, Eric; Boelen, Anita

    2016-04-01

    The diaphragm is the main respiratory muscle, and its function is compromised during severe illness. Altered local thyroid hormone (TH) metabolism may be a determinant of impaired muscle function during illness. This study investigates the effects of bacterial sepsis and chronic inflammation on muscle fiber type, local TH metabolism, and mitochondrial function in the diaphragm. Two mouse models were used: sepsis induced by S. pneumoniae infection or chronic inflammation induced by subcutaneous turpentine injection. In vitro, the effect of bacterial endotoxin (LPS) on mitochondrial function in C2C12 myotubes was studied. Sepsis induced a transient increase in the fiber type I profile and increased Dio3 expression while decreasing Dio2, Thra1, and Slc16a2 expression. Triiodothyronine positively regulated genes Tnni2 and Myog were decreased, indicating reduced TH signaling in the diaphragm. In contrast, chronic inflammation increased the fiber type II profile in the diaphragm as well as Thra1, Thrb1, and Myog expression while decreasing Dio3 expression, suggesting increased TH responsiveness during chronic inflammation. LPS-stimulated C2C12 myotubes showed decreased Dio2 expression and reduced basal oxygen consumption as well as non-mitochondrial respiration. The same respiratory profile was induced by Dio2 knockdown in myotubes. The in vivo results show differential effects of sepsis and chronic inflammation on diaphragm muscle fiber type, TH metabolism, and mitochondrial function, while the in vitro results point to a causal role for altered TH metabolism in functional muscle impairment. These findings may be relevant for the pathogenesis of impaired respiratory function in critical illness.

  12. The effect of dietary fat content on phospholipid fatty acid profile is muscle fiber type dependent.

    PubMed

    Janovská, Alena; Hatzinikolas, George; Mano, Mark; Wittert, Gary A

    2010-04-01

    A high-saturated-fat diet (HFD) induces obesity and insulin resistance (IR). IR has been linked to alterations and increased saturation in the phospholipid composition of skeletal muscles. We aimed to determine whether HFD feeding affects fatty acid (FA) membrane profile in a muscle fiber type-specific manner. We measured phospholipid FAs and expression of FA synthesis genes in oxidative soleus (SOL) and glycolytic extensor digitorum longus (EDL) muscles from rats fed either standard chow (standard laboratory diet, SLD) or a HFD. The HFD increased fat mass, plasma insulin, and leptin levels. Compared with EDL, SOL muscles preferentially accumulated C18 over C16 FAs and n-6 over n-3 polyunsaturated FAs (PUFAs) on either diet. With the HFD, SOL muscles contained more n-9 monounsaturated FAs (MUFAs) and n-6 PUFAs and less n-7 MUFAs and n-3 PUFAs than EDL muscles and had lower unsaturation index, a pattern known to be associated with IR. Stearoyl-CoA desaturase-1 expression was approximately 13-fold greater in EDL than in SOL muscles but did not change with the HFD in either muscle. The expression of Elongase-5 was higher, and that of Elongase-6 (Elovl6) was lower in EDL compared with SOL muscles with both diets. In EDL muscles, the expression of Elovl6 was lower in the HFD than in the SLD. The pattern of FA uptake, expression, and diet-induced changes in FA desaturating and elongating enzymes maintained higher FA unsaturation in EDL muscles. Accordingly, the fiber type composition of skeletal muscles and their distribution may be important in the development and progression of obesity and IR.

  13. The increase in fiber size in male rat gastrocnemius after chronic central leptin infusion is related to activation of insulin signaling.

    PubMed

    Burgos-Ramos, Emma; Canelles, Sandra; Rodríguez, Amaia; Frago, Laura M; Gómez-Ambrosi, Javier; Chowen, Julie A; Frühbeck, Gema; Argente, Jesús; Barrios, Vicente

    2018-07-15

    Insulin potentiates leptin effects on muscle accrual and glucose homeostasis. However, the relationship between leptin's central effects on peripheral insulin sensitivity and the associated structural changes remain unclear. We hypothesized that central leptin infusion modifies muscle size through activation of insulin signaling. Muscle insulin signaling, enzymes of fatty acid metabolism, mitochondrial respiratory chain complexes, proliferating cell nuclear antigen (PCNA) and fiber area were analyzed in the gastrocnemius of chronic central infused (L), pair-fed (PF) and control rats. PCNA-positive nuclei, fiber area, GLUT4 and glycogen levels and activation of Akt and mechanistic target of rapamycin were increased in L, with no changes in PF. Acetyl-CoA carboxylase-β mRNA levels and non-esterified fatty acid and triglyceride content were reduced and carnitine palmitoyltransferase-1b expression and mitochondrial complexes augmented in L. These results suggest that leptin promotes an increase in muscle size associated with improved insulin signaling favored by lipid profile. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Afferent control mechanisms involved in the development of soleus fiber alterations in simulated hypogravity

    NASA Astrophysics Data System (ADS)

    Shenkman, B. S.; Nemirovskaya, T. L.; Shapovalova, K. B.; Podlubnaya, Z. A.; Vikhliantsev, I. M.; Moukhina, A. M.; Kozlovskaya, I. B.

    2007-02-01

    It was recently established that support withdrawal (withdrawal of support reaction force) in microgravity provokes a sequence of functional shifts in the activity of motor units (inactivation of slow ones) and peripheral muscle apparatus which lead to the decline of postural muscle contractility and alterations in fiber characteristics. However, mechanisms involved in inactivation of the slow motor units and appropriate slow-twitch muscle fiber disuse under the supportless conditions remained unknown. We show here that artificial inactivation of muscles-antagonists (which are known to be hyperactive during unloading) counteracts some of the unloading-induced events in the rat soleus (fiber size reduction, slow-to-fast fiber-type transition and decline of titin and nebulin content). It was also demonstrated that direct activation of the muscarinic receptors of the neostriatum neurons prevented slow-to-fast fiber-type transformation in soleus of hindlimb suspended rats.

  15. An analysis of the relationships between subthreshold electrical properties and excitability in skeletal muscle

    PubMed Central

    L.-H. Huang, Christopher; Fraser, James A.

    2011-01-01

    Skeletal muscle activation requires action potential (AP) initiation followed by its sarcolemmal propagation and tubular excitation to trigger Ca2+ release and contraction. Recent studies demonstrate that ion channels underlying the resting membrane conductance (GM) of fast-twitch mammalian muscle fibers are highly regulated during muscle activity. Thus, onset of activity reduces GM, whereas prolonged activity can markedly elevate GM. Although these observations implicate GM regulation in control of muscle excitability, classical theoretical studies in un-myelinated axons predict little influence of GM on membrane excitability. However, surface membrane morphologies differ markedly between un-myelinated axons and muscle fibers, predominantly because of the tubular (t)-system of muscle fibers. This study develops a linear circuit model of mammalian muscle fiber and uses this to assess the role of subthreshold electrical properties, including GM changes during muscle activity, for AP initiation, AP propagation, and t-system excitation. Experimental observations of frequency-dependent length constant and membrane-phase properties in fast-twitch rat fibers could only be replicated by models that included t-system luminal resistances. Having quantified these resistances, the resulting models showed enhanced conduction velocity of passive current flow also implicating elevated AP propagation velocity. Furthermore, the resistances filter passive currents such that higher frequency current components would determine sarcolemma AP conduction velocity, whereas lower frequency components excite t-system APs. Because GM modulation affects only the low-frequency membrane impedance, the GM changes in active muscle would predominantly affect neuromuscular transmission and low-frequency t-system excitation while exerting little influence on the high-frequency process of sarcolemmal AP propagation. This physiological role of GM regulation was increased by high Cl− permeability

  16. Finite element analysis of mechanics of lateral transmission of force in single muscle fiber.

    PubMed

    Zhang, Chi; Gao, Yingxin

    2012-07-26

    Most of the myofibers in long muscles of vertebrates terminate within fascicles without reaching either end of the tendon, thus force generated in myofibers has to be transmitted laterally through the extracellular matrix (ECM) to adjacent fibers; which is defined as the lateral transmission of force in skeletal muscles. The goal of this study was to determine the mechanisms of lateral transmission of force between the myofiber and ECM. In this study, a 2D finite element model of single muscle fiber was developed to study the effects of mechanical properties of the endomysium and the tapered ends of myofiber on lateral transmission of force. Results showed that most of the force generated is transmitted near the end of the myofiber through shear to the endomysium, and the force transmitted to the end of the model increases with increased stiffness of ECM. This study also demonstrated that the tapered angle of the myofiber ends can reduce the stress concentration near the myofiber end while laterally transmitting force efficiently. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Acute antioxidant supplementation and skeletal muscle vascular conductance in aged rats: role of exercise and fiber type.

    PubMed

    Hirai, Daniel M; Copp, Steven W; Schwagerl, Peter J; Haub, Mark D; Poole, David C; Musch, Timothy I

    2011-04-01

    Age-related increases in oxidative stress contribute to impaired skeletal muscle vascular control. However, recent evidence indicates that antioxidant treatment with tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) attenuates flow-mediated vasodilation in isolated arterioles from the highly oxidative soleus muscle of aged rats. Whether antioxidant treatment with tempol evokes similar responses in vivo at rest and during exercise in senescent individuals and whether this effect varies based on muscle fiber type composition are unknown. We tested the hypothesis that redox modulation via acute systemic tempol administration decreases vascular conductance (VC) primarily in oxidative hindlimb locomotor muscles at rest and during submaximal whole body exercise (treadmill running at 20 m/min, 5% grade) in aged rats. Eighteen old (25-26 mo) male Fischer 344 x Brown Norway rats were assigned to either rest (n = 8) or exercise (n = 10) groups. Regional VC was determined via radiolabeled microspheres before and after intra-arterial administration of tempol (302 μmol/kg). Tempol decreased mean arterial pressure significantly by 9% at rest and 16% during exercise. At rest, similar VC in 26 out of 28 individual hindlimb muscles or muscle parts following tempol administration compared with control resulted in unchanged total hindlimb muscle VC (control: 0.18 ± 0.02; tempol: 0.17 ± 0.05 ml·min(-1)·100 g(-1)·mmHg(-1); P > 0.05). During exercise, all individual hindlimb muscles or muscle parts irrespective of fiber type composition exhibited either an increase or no change in VC with tempol (i.e., ↑11 and ↔17 muscles or muscle parts), such that total hindlimb VC increased by 25% (control: 0.93 ± 0.04; tempol: 1.15 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1); P ≤ 0.05). These results demonstrate that acute systemic administration of the antioxidant tempol significantly impacts the control of regional vascular tone in vivo presumably via redox modulation and improves

  18. Regenerative capability of skeletal muscle in chicken muscular dystrophy.

    PubMed

    Nonaka, I; Fujita, T; Sugita, H

    1984-06-01

    To examine the morphological sequence of regenerating fibers after myonecrosis in dystrophic muscles, 0.5 ml of 0.5% bupivacaine hydrochloride (BPVC) (Marcaine) solution, a local anesthetic with a cytotoxic effect on the muscle fibers, was injected directly into the dystrophic (line 413) and nondystrophic (line 412) posterior latissimus dorsi (PLD) muscles of young and adult chickens. Although the dystrophic muscles after BPVC injection showed a rapid recovery with a similar tempo to that of nondystrophic ones, they showed different morphological behavior in the early phase of regeneration, including marked variability in the size of fibers and in the intracytoplasmic enzyme activities of nicotinamide adenine dinucleotide, reduced-tetrazolium reductase (NADH-TR), acetylcholinesterase (AChE), and nonspecific esterase (NSE).

  19. Muscle activation patterns and motor anatomy of Anna's hummingbirds Calypte anna and zebra finches Taeniopygia guttata.

    PubMed

    Donovan, Edward R; Keeney, Brooke K; Kung, Eric; Makan, Sirish; Wild, J Martin; Altshuler, Douglas L

    2013-01-01

    Flying animals exhibit profound transformations in anatomy, physiology, and neural architecture. Although much is known about adaptations in the avian skeleton and musculature, less is known about neuroanatomy and motor unit integration for bird flight. Hummingbirds are among the most maneuverable and specialized of vertebrate fliers, and two unusual neuromuscular features have been previously reported: (1) the pectoralis major has a unique distribution pattern of motor end plates (MEPs) compared with all other birds and (2) electromyograms (EMGs) from the hummingbird's pectoral muscles, the pectoralis major and the supracoracoideus, show activation bursts composed of one or a few spikes that appear to have a very consistent pattern. Here, we place these findings in a broader context by comparing the MEPs, EMGs, and organization of the spinal motor neuron pools of flight muscles of Anna's hummingbird Calypte anna, zebra finches Taeniopygia guttata, and, for MEPs, several other species. The previously shown MEP pattern of the hummingbird pectoralis major is not shared with its closest taxonomic relative, the swift, and appears to be unique to hummingbirds. MEP arrangements in previously undocumented wing muscles show patterns that differ somewhat from other avian muscles. In the parallel-fibered strap muscles of the shoulder, MEP patterns appear to relate to muscle length, with the smallest muscles having fibers that span the entire muscle. MEP patterns in pennate distal wing muscles were the same regardless of size, with tightly clustered bands in the middle portion of the muscle, not evenly distributed bands over the muscle's entire length. Muscle activations were examined during slow forward flight in both species, during hovering in hummingbirds, and during slow ascents in zebra finches. The EMG bursts of a wing muscle, the pronator superficialis, were highly variable in peak number, size, and distribution across wingbeats for both species. In the pectoralis

  20. Advanced age-related denervation and fiber-type grouping in skeletal muscle of SOD1 knockout mice.

    PubMed

    Kostrominova, Tatiana Y

    2010-11-30

    In this study skeletal muscles from 1.5- and 10-month-old Cu/Zn superoxide dismutase (SOD1) homozygous knockout (JLSod1(-/-)) mice obtained from The Jackson Laboratory (C57Bl6/129SvEv background) were compared with muscles from age- and sex-matched heterozygous (JLSod1(+/-)) littermates. The results of this study were compared with previously published data on two different strains of Sod1(-/-) mice: one from Dr. Epstein's laboratory (ELSod1(-/-); C57Bl6 background) and the other from Cephalon, Inc. (CSod1(-/-); 129/CD-1 background). Grouping of succinate dehydrogenase-positive fibers characterized muscles of Sod1(-/-) mice from all three strains. The 10-month-old Sod1(-/-)C and JL mice displayed pronounced denervation of the gastrocnemius muscle, whereas the ELSod1(-/-) mice displayed a small degree of denervation at this age, but developed accelerated age-related denervation later on. Denervation markers were up-regulated in skeletal muscle of 10-month-old JLSod1(-/-) mice. This study is the first to show that metallothionein mRNA and protein expression was up-regulated in the skeletal muscle of 10-month-old JLSod1(-/-) mice and was mostly localized to the small atrophic muscle fibers. In conclusion, all three strains of Sod1(-/-) mice develop accelerated age-related muscle denervation, but the genetic background has significant influence on the progress of denervation. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Common neural structures activated by epidural and transcutaneous lumbar spinal cord stimulation: Elicitation of posterior root-muscle reflexes

    PubMed Central

    Freundl, Brigitta; Binder, Heinrich; Minassian, Karen

    2018-01-01

    Epidural electrical stimulation of the lumbar spinal cord is currently regaining momentum as a neuromodulation intervention in spinal cord injury (SCI) to modify dysregulated sensorimotor functions and augment residual motor capacity. There is ample evidence that it engages spinal circuits through the electrical stimulation of large-to-medium diameter afferent fibers within lumbar and upper sacral posterior roots. Recent pilot studies suggested that the surface electrode-based method of transcutaneous spinal cord stimulation (SCS) may produce similar neuromodulatory effects as caused by epidural SCS. Neurophysiological and computer modeling studies proposed that this noninvasive technique stimulates posterior-root fibers as well, likely activating similar input structures to the spinal cord as epidural stimulation. Here, we add a yet missing piece of evidence substantiating this assumption. We conducted in-depth analyses and direct comparisons of the electromyographic (EMG) characteristics of short-latency responses in multiple leg muscles to both stimulation techniques derived from ten individuals with SCI each. Post-activation depression of responses evoked by paired pulses applied either epidurally or transcutaneously confirmed the reflex nature of the responses. The muscle responses to both techniques had the same latencies, EMG peak-to-peak amplitudes, and waveforms, except for smaller responses with shorter onset latencies in the triceps surae muscle group and shorter offsets of the responses in the biceps femoris muscle during epidural stimulation. Responses obtained in three subjects tested with both methods at different time points had near-identical waveforms per muscle group as well as same onset latencies. The present results strongly corroborate the activation of common neural input structures to the lumbar spinal cord—predominantly primary afferent fibers within multiple posterior roots—by both techniques and add to unraveling the basic mechanisms

  2. Effect of heat shock preconditioning on ROS scavenging activity in rat skeletal muscle after downhill running.

    PubMed

    Shima, Yosuke; Kitaoka, Katsuhiko; Yoshiki, Yumiko; Maruhashi, Yoshinobu; Tsuyama, Takeshi; Tomita, Katsuro

    2008-10-01

    The mechanisms of the protective effect conferred by heat shock preconditioning (HS) are currently unknown. The purpose of this study was to determine the effect of HS on muscle injury after downhill running and to address the mechanism of the effect. Female Wistar rats were assigned to three groups: HS, downhill running (E), and downhill running after heat shock preconditioning (HS + E). The HS and HS + E rats were placed in a heat chamber for 60 min (ambient temperature 42 +/- 1.0 degrees C) 48 h before downhill running. Reactive oxygen species (ROS) scavenging activity was determined by electron spin resonance (ESR), and heat shock protein 72 (HSP72) mRNA expression was measured in rat quadriceps femoris. Leukocyte infiltration and degenerated muscle fibers were determined histopathologically. ROS scavenging activity significantly increased at 3 days after HS (151 +/- 18%) and HSP72 mRNA expression increased immediately after HS (1750 +/- 1914%). No decrease in ROS scavenging activity was observed in the HS + E rats at 2 days after exercise compared with the E rats (102 +/- 9% vs. 79 +/- 5%). Degenerated muscle fibers in HS + E rats were significantly less than in E rats at 2, 3, and 7 days after exercise (0.8 +/- 1.0 vs. 2.8 +/- 1.6, 0.8 +/- 1.0 vs. 1.8 +/- 1.6, 0 vs. 0.3 +/- 0.6, respectively). These data demonstrated that HS can reduce muscle injury after downhill running, and this effect may be mediated by increased ROS scavenging activity. Furthermore, HS may protect the antioxidant defense system in skeletal muscle by enhancing the adaptive HSP72 mRNA response.

  3. Muscle mechanics: adaptations with exercise-training.

    PubMed

    Fitts, R H; Widrick, J J

    1996-01-01

    Based on the MHC isoform pattern, adult mammalian limb skeletal muscles contain two and, in some species, three types of fast fibers (Type IIa, IIx, and IIb), and one slow fiber (Type I). Slow muscles, such as the soleus, contain primarily the slow Type I fiber, whereas fast-twitch muscles are composed primarily of a mixture of the fast myosin isozymes. Force generation involves cross-bridge interaction and transition from a weakly bound, low-force state (AM-ADP-P(i)) to the strongly bound, high-force state (AM-ADP). This transition is thought to be rate limiting in terms of dP/dt, and the high-force state is the dominant cross-bridge form during a peak isometric contraction. Intact fast and slow skeletal muscles generate approximately the same amount of peak force (Po) of between 200 and 250 kN.m-2. However, the rate of transition from the low- to high-force state shows Ca2+ sensitivity and is 7-fold higher in fast-twitch, as compared to slow-twitch, skeletal muscle fibers. Fiber Vo or the maximal cross-bridge cycle rate is highly correlated with and thought to be dependent on the specific activity of the myosin or myofibrillar ATPase. The hierarchy for Vo is the Type IIb > IIx > IIa > I. This functional difference for the fast fiber types explains the higher Vo observed in the predominantly Type IIb SVL vs. the mixed fast Type IIa and IIb EDL muscle. A plot of Vo vs. species size demonstrates that an inverse relationship exists between Vo and body mass. From the standpoint of work capacity, the important property is power output. An analysis of individual muscles indicates that peak power is obtained at loads considerably below 50% of Po. Individuals with a high percentage of fast-twitch fibers generate a greater torque and higher power at a given velocity than those with predominantly slow-twitch fibers. In humans, mean peak power occurred in a ratio of 10:5:1 for the Type IIb, IIa, and I fibers. The in vivo measurement of the torque-velocity relationship and

  4. Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase

    PubMed Central

    Berthier, Christine; Kutchukian, Candice; Bouvard, Clément; Okamura, Yasushi

    2015-01-01

    Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P2 in Ca2+ homeostasis and excitation–contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein–tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca2+ transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca2+ release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP–expressing fibers challenged by 5-s-long depolarizing pulses, the Ca2+ level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP–expressing fibers showed a reversible depression of Ca2+ release during trains, with the peak Ca2+ transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP–expressing fibers. Cav1.1 Ca2+ channel–mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ1PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule–bound PLCδ1PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers

  5. Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase.

    PubMed

    Berthier, Christine; Kutchukian, Candice; Bouvard, Clément; Okamura, Yasushi; Jacquemond, Vincent

    2015-04-01

    Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P2 in Ca(2+) homeostasis and excitation-contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein-tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca(2+) transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca(2+) release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP-expressing fibers challenged by 5-s-long depolarizing pulses, the Ca(2+) level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP-expressing fibers showed a reversible depression of Ca(2+) release during trains, with the peak Ca(2+) transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP-expressing fibers. Cav1.1 Ca(2+) channel-mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ1PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule-bound PLCδ1PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers

  6. How the Brain May Have Shaped Muscle Anatomy and Physiology: A Preliminary Study.

    PubMed

    Muchlinski, Magdalena N; Hemingway, Holden W; Pastor, Juan; Omstead, Kailey M; Burrows, Anne M

    2018-03-01

    Skeletal muscle fibers are often used to evaluate functional differences in locomotion. However, because there are energetic differences among muscle fiber cells, muscle fiber composition could be used to address evolutionary questions about energetics. Skeletal muscle is composed of two main types of fibers: Type I and II. The difference between the two can be reduced to how these muscle cells use oxygen and glucose. Type I fibers convert glucose to ATP using oxygen, while Type II fibers rely primarily on anaerobic metabolic processes. The expensive tissue hypothesis (ETH) proposes that the energetic demands imposed on the body by the brain result in a reduction in other expensive tissues (e.g., gastrointestinal tract). The original ETH dismisses the energetic demands of skeletal muscle, despite skeletal muscle being (1) an expensive tissue when active and (2) in direct competition for glucose with the brain. Based on these observations we hypothesize that larger brained primates will have relatively less muscle mass and a decrease in Type I fibers. As part of a larger study to test this hypothesis, we present data from 10 species of primates. We collected body mass, muscle mass, and biopsied four muscles from each specimen for histological procedures. We collected endocranial volumes from the literature. Using immunohistochemistry, a muscle fiber composition profile was created for each species sampled. Results show that larger brained primates have less muscle and fewer Type I fibers than primates with smaller brains. Results clarify the relationship between muscle mass and brain mass and illustrate how muscle mass could be used to address energetic questions. Anat Rec, 301:528-537, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  7. Difference in muscle activation patterns during high-speed versus standard-speed yoga: A randomized sequence crossover study.

    PubMed

    Potiaumpai, Melanie; Martins, Maria Carolina Massoni; Wong, Claudia; Desai, Trusha; Rodriguez, Roberto; Mooney, Kiersten; Signorile, Joseph F

    2017-02-01

    To compare the difference in muscle activation between high-speed yoga and standard-speed yoga and to compare muscle activation of the transitions between poses and the held phases of a yoga pose. Randomized sequence crossover trial SETTING: A laboratory of neuromuscular research and active aging Interventions: Eight minutes of continuous Sun Salutation B was performed, at a high speed versus a standard-speed, separately. Electromyography was used to quantify normalized muscle activation patterns of eight upper and lower body muscles (pectoralis major, medial deltoids, lateral head of the triceps, middle fibers of the trapezius, vastus medialis, medial gastrocnemius, thoracic extensor spinae, and external obliques) during the high-speed and standard-speed yoga protocols. Difference in normalized muscle activation between high-speed yoga and standard-speed yoga. Normalized muscle activity signals were significantly higher in all eight muscles during the transition phases of poses compared to the held phases (p<0.01). There was no significant interaction between speed×phase; however, greater normalized muscle activity was seen for highspeed yoga across the entire session. Our results show that transitions from one held phase of a pose to another produces higher normalized muscle activity than the held phases of the poses and that overall activity is greater during highspeed yoga than standard-speed yoga. Therefore, the transition speed and associated number of poses should be considered when targeting specific improvements in performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Effects of muscle fiber type on glycolytic potential and meat quality traits in different Tibetan pig muscles and their association with glycolysis-related gene expression.

    PubMed

    Shen, L Y; Luo, J; Lei, H G; Jiang, Y Z; Bai, L; Li, M Z; Tang, G Q; Li, X W; Zhang, S H; Zhu, L

    2015-11-13

    The myosin heavy chain (MyHC) composition, glycolytic potential, mitochondrial content, and gene expression related to energy metabolism were analyzed in eight muscles from Tibetan pigs, to study how meat quality develops in different muscle tissues. The muscles were classified into three clusters, based on MyHC composition: masseter, trapezius, and latissimus dorsi as 'slow-oxidative-type'; psoas major and semimembranosus as 'intermediate-type'; and longissimus dorsi, obliquus externus abdominis, and semitendinosus as 'fast-glycolytic-type'. The 'slow-oxidative-type' muscles had the highest MyHC I and MyHC IIA content (P < 0.01); 'intermediate-type' muscles, the highest MyHC IIx content (P < 0.01); and 'fast-glycolytic-type' muscles, the highest MyHC IIb content (P < 0.01). The pH values measured in 'slow-oxidative-type' muscles were higher than those in the other clusters were; however, the color of 'fast-glycolytic-type' muscles was palest (P < 0.01). Mitochondrial content increased in the order: fast-glycolytic-type < intermediate-type < slow-oxidative-type. In the 'slow-oxidative-type' muscles, the expression levels of genes related to ATP synthesis were higher, but were lower for those related to glycogen synthesis and glycolysis. Mitochondrial content was significantly positively correlated with MyHC I content, but negatively correlated with MyHC IIb content. MyHC I and mitochondrial content were both negatively correlated with glycolytic potential. Overall, muscles used frequently in exercise had a higher proportion of type I fibers. 'Slow-oxidative-type' muscles, rich in type I fibers with higher mitochondrial and lower glycogen and glucose contents, had a higher ATP synthesis efficiency and lower glycolytic capacity, which contributed to their superior meat quality.

  9. Muscle-Specific SIRT1 Gain-of-Function Increases Slow-Twitch Fibers and Ameliorates Pathophysiology in a Mouse Model of Duchenne Muscular Dystrophy

    PubMed Central

    Chalkiadaki, Angeliki; Igarashi, Masaki; Nasamu, Armiyaw Sebastian; Knezevic, Jovana; Guarente, Leonard

    2014-01-01

    SIRT1 is a metabolic sensor and regulator in various mammalian tissues and functions to counteract metabolic and age-related diseases. Here we generated and analyzed mice that express SIRT1 at high levels specifically in skeletal muscle. We show that SIRT1 transgenic muscle exhibits a fiber shift from fast-to-slow twitch, increased levels of PGC-1α, markers of oxidative metabolism and mitochondrial biogenesis, and decreased expression of the atrophy gene program. To examine whether increased activity of SIRT1 protects from muscular dystrophy, a muscle degenerative disease, we crossed SIRT1 muscle transgenic mice to mdx mice, a genetic model of Duchenne muscular dystrophy. SIRT1 overexpression in muscle reverses the phenotype of mdx mice, as determined by histology, creatine kinase release into the blood, and endurance in treadmill exercise. In addition, SIRT1 overexpression also results in increased levels of utrophin, a functional analogue of dystrophin, as well as increased expression of PGC-1α targets and neuromuscular junction genes. Based on these findings, we suggest that pharmacological interventions that activate SIRT1 in skeletal muscle might offer a new approach for treating muscle diseases. PMID:25032964

  10. Effect of spaceflight on the isotonic contractile properties of single skeletal muscle fibers in the rhesus monkey

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Romatowski, J. G.; Blaser, C.; De La Cruz, L.; Gettelman, G. J.; Widrick, J. J.

    2000-01-01

    Experiments from both Cosmos and Space Shuttle missions have shown weightlessness to result in a rapid decline in the mass and force of rat hindlimb extensor muscles. Additionally, despite an increased maximal shortening velocity, peak power was reduced in rat soleus muscle post-flight. In humans, declines in voluntary peak isometric ankle extensor torque ranging from 15-40% have been reported following long- and short-term spaceflight and prolonged bed rest. Complete understanding of the cellular events responsible for the fiber atrophy and the decline in force, as well as the development of effective countermeasures, will require detailed knowledge of how the physiological and biochemical processes of muscle function are altered by spaceflight. The specific purpose of this investigation was to determine the extent to which the isotonic contractile properties of the slow- and fast-twitch fiber types of the soleus and gastrocnemius muscles of rhesus monkeys (Macaca mulatta) were altered by a 14-day spaceflight.

  11. Physiological changes in fast and slow muscle with simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Dettbarn, W. D.; Misulis, K. E.

    1984-01-01

    A rat hindlimb suspension model of simulated weightlessness was used to examine the physiological characteristics of skeletal muscle. The physiological sequelae of hindlimb suspension were compared to those of spinal cord section, denervation by sciatic nerve crush, and control. Muscle examined were the predominantly slow (Type 1) soleus (SOL) and the predominantly fast (Type 2) extensor digitorum longus (EDL). Two procedures which alter motor unit activity, hindlimb suspension and spinal cord section, produce changes in characteristics of skeletal muscles that are dependent upon fiber type. The SOL develops characteristics more representative of a fast muscle, including smaller Type 1 fiber proportion and higher AChE activity. The EDL, which is already predominantly fast, loses most of its few Type 1 fibers, thus also becoming faster. These data are in agreement with the studies in which rats experienced actual weightlessness.

  12. When phosphorylated at Thr148, the β2-subunit of AMP-activated kinase does not associate with glycogen in skeletal muscle.

    PubMed

    Xu, Hongyang; Frankenberg, Noni T; Lamb, Graham D; Gooley, Paul R; Stapleton, David I; Murphy, Robyn M

    2016-07-01

    The 5'-AMP-activated protein kinase (AMPK), a heterotrimeric complex that functions as an intracellular fuel sensor that affects metabolism, is activated in skeletal muscle in response to exercise and utilization of stored energy. The diffusibility properties of α- and β-AMPK were examined in isolated skeletal muscle fiber segments dissected from rat fast-twitch extensor digitorum longus and oxidative soleus muscles from which the surface membranes were removed by mechanical dissection. After the muscle segments were washed for 1 and 10 min, ∼60% and 75%, respectively, of the total AMPK pools were found in the diffusible fraction. After in vitro stimulation of the muscle, which resulted in an ∼80% decline in maximal force, 20% of the diffusible pool became bound in the fiber. This bound pool was not associated with glycogen, as determined by addition of a wash step containing amylase. Stimulation of extensor digitorum longus muscles resulted in 28% glycogen utilization and a 40% increase in phosphorylation of the downstream AMPK target acetyl carboxylase-CoA. This, however, had no effect on the proportion of total β2-AMPK that was phosphorylated in whole muscle homogenates measured by immunoprecipitation. These findings suggest that, in rat skeletal muscle, β2-AMPK is not associated with glycogen and that activation of AMPK by muscle contraction does not dephosphorylate β2-AMPK. These findings question the physiological relevance of the carbohydrate-binding function of β2-AMPK in skeletal muscle. Copyright © 2016 the American Physiological Society.

  13. Identification and functional characterization of muscle satellite cells in Drosophila

    PubMed Central

    Reichert, Heinrich

    2017-01-01

    Work on genetic model systems such as Drosophila and mouse has shown that the fundamental mechanisms of myogenesis are remarkably similar in vertebrates and invertebrates. Strikingly, however, satellite cells, the adult muscle stem cells that are essential for the regeneration of damaged muscles in vertebrates, have not been reported in invertebrates. In this study, we show that lineal descendants of muscle stem cells are present in adult muscle of Drosophila as small, unfused cells observed at the surface and in close proximity to the mature muscle fibers. Normally quiescent, following muscle fiber injury, we show that these cells express Zfh1 and engage in Notch-Delta-dependent proliferative activity and generate lineal descendant populations, which fuse with the injured muscle fiber. In view of strikingly similar morphological and functional features, we consider these novel cells to be the Drosophila equivalent of vertebrate muscle satellite cells. PMID:29072161

  14. Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4.

    PubMed

    Bullard, Steven A; Seo, Seongjin; Schilling, Birgit; Dyle, Michael C; Dierdorff, Jason M; Ebert, Scott M; DeLau, Austin D; Gibson, Bradford W; Adams, Christopher M

    2016-08-19

    Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. The Promotion of a Functional Fibrosis in Skeletal Muscle with Volumetric Muscle Loss Injury Following the Transplantation of Muscle-ECM

    DTIC Science & Technology

    2013-02-04

    i.e., volumetric muscle loss; VML). The explicit goal is to restore functional capacity to the injured tissue by promoting generation of muscle fibers ...3,23,25,27,28]. As a result, trans- plantation of a variety of ECMs in preclinical animal models has resulted in modest levels of muscle fiber generation at...the site of the defect during the initial months post-injury [20,28e30]. However, an apparent enhanced rate of muscle fiber generation at

  16. The fraction of myosin motors that participate in isometric contraction of rabbit muscle fibers at near-physiological temperature.

    PubMed

    Tsaturyan, Andrey K; Bershitsky, Sergey Y; Koubassova, Natalia A; Fernandez, Manuel; Narayanan, Theyencheri; Ferenczi, Michael A

    2011-07-20

    The duty ratio, or the part of the working cycle in which a myosin molecule is strongly attached to actin, determines motor processivity and is required to evaluate the force generated by each molecule. In muscle, it is equal to the fraction of myosin heads that are strongly, or stereospecifically, bound to the thin filaments. Estimates of this fraction during isometric contraction based on stiffness measurements or the intensities of the equatorial or meridional x-ray reflections vary significantly. Here, we determined this value using the intensity of the first actin layer line, A1, in the low-angle x-ray diffraction patterns of permeable fibers from rabbit skeletal muscle. We calibrated the A1 intensity by considering that the intensity in the relaxed and rigor states corresponds to 0% and 100% of myosin heads bound to actin, respectively. The fibers maximally activated with Ca(2+) at 4°C were heated to 31-34°C with a Joule temperature jump (T-jump). Rigor and relaxed-state measurements were obtained on the same fibers. The intensity of the inner part of A1 during isometric contraction compared with that in rigor corresponds to 41-43% stereospecifically bound myosin heads at near-physiological temperature, or an average force produced by a head of ~6.3 pN. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Optical fiber sensor having an active core

    NASA Technical Reports Server (NTRS)

    Egalon, Claudio Oliveira (Inventor); Rogowski, Robert S. (Inventor)

    1993-01-01

    An optical fiber is provided. The fiber is comprised of an active fiber core which produces waves of light upon excitation. A factor ka is identified and increased until a desired improvement in power efficiency is obtained. The variable a is the radius of the active fiber core and k is defined as 2 pi/lambda wherein lambda is the wavelength of the light produced by the active fiber core. In one embodiment, the factor ka is increased until the power efficiency stabilizes. In addition to a bare fiber core embodiment, a two-stage fluorescent fiber is provided wherein an active cladding surrounds a portion of the active fiber core having an improved ka factor. The power efficiency of the embodiment is further improved by increasing a difference between the respective indices of refraction of the active cladding and the active fiber core.

  18. Laser ablation of Drosophila embryonic motoneurons causes ectopic innervation of target muscle fibers

    NASA Technical Reports Server (NTRS)

    Chang, T. N.; Keshishian, H.

    1996-01-01

    We have tested the effects of neuromuscular denervation in Drosophila by laser-ablating the RP motoneurons in intact embryos before synaptogenesis. We examined the consequences of this ablation on local synaptic connectivity in both 1st and 3rd instar larvae. We find that the partial or complete loss of native innervation correlates with the appearance of alternate inputs from neighboring motor endings and axons. These collateral inputs are found at ectopic sites on the denervated target muscle fibers. The foreign motor endings are electrophysiologically functional and are observed on the denervated muscle fibers by the 1st instar larval stage. Our data are consistent with the existence of a local signal from the target environment, which is regulated by innervation and influences synaptic connectivity. Our results show that, despite the stereotypy of Drosophila neuromuscular connections, denervation can induce local changes in connectivity in wild-type Drosophila, suggesting that mechanisms of synaptic plasticity may also be involved in normal Drosophila neuromuscular development.

  19. Metabolic adaptation of skeletal muscles to gravitational unloading

    NASA Astrophysics Data System (ADS)

    Ohira, Y.; Yasui, W.; Kariya, F.; Wakatsuki, T.; Nakamura, K.; Asakura, T.; Edgerton, V. R.

    Responses of high-energy phosphates and metabolic properties to hindlimb suspension were studied in adult rats. The relative content of phosphocreatine (PCr) in the calf muscles was significantly higher in rats suspended for 10 days than in age-matched cage controls. The Pi/PCr ratio, where Pi is inorganic phosphate, in suspended muscles was less than controls. The absolute weights of soleus and medial gastrocnemius (MG) were approximately 40% less than controls. Although the % fiber distribution in MG was unchanged, the % slow fibers decreased and the % fibers which were classified as both slow and fast was increased in soleus. The activities (per unit weight or protein) of succinate dehydrogenase and lactate dehydrogenase in soleus were unchanged but those of cytochrome oxidase, β-hydroxyacyl CoA dehydrogenase, and citrate synthase were decreased following unloading. None of these enzyme activities in MG changed. However, the total levels of all enzymes in whole muscles decreased by suspension. It is suggested that shift of slow muscle toward fast type by unloading is associated with a decrease in mitochondrial biogenesis. Further, gravitational unloading affected the levels of muscle proteins differently even in the same mitochondrial enzymes. Unloading-related atrophy is prominent in red muscle or slow-twitch fiber 1, 2. Such atrophy is accompanied by a shift of contractile properties toward fast-twitch type 2-9. Further, inhibition of mitochondrial metabolism in these muscles is also reported by some studies 10-14 suggesting a lowered mitochondrial biogenesis, although results from some studies do not necessarily agree 1, 7, 15. However, the precise mechanism responsible for such alterations of muscle properties in response to gravitational unloading is unclear. On the contrary, mitochondrial biogenesis, suggested by mitochondrial enzyme activities and/or mass, is stimulated in muscles with depleted high-energy phosphates by cold exposure 16 and/or by feeding

  20. Fluorescence-based measurement of store-operated calcium entry in live cells: from cultured cancer cell to skeletal muscle fiber.

    PubMed

    Pan, Zui; Zhao, Xiaoli; Brotto, Marco

    2012-02-13

    Store operated Ca(2+) entry (SOCE), earlier termed capacitative Ca(2+) entry, is a tightly regulated mechanism for influx of extracellular Ca(2+) into cells to replenish depleted endoplasmic reticulum (ER) or sarcoplasmic reticulum (SR) Ca(2+) stores. Since Ca(2+) is a ubiquitous second messenger, it is not surprising to see that SOCE plays important roles in a variety of cellular processes, including proliferation, apoptosis, gene transcription and motility. Due to its wide occurrence in nearly all cell types, including epithelial cells and skeletal muscles, this pathway has received great interest. However, the heterogeneity of SOCE characteristics in different cell types and the physiological function are still not clear. The functional channel properties of SOCE can be revealed by patch-clamp studies, whereas a large body of knowledge about this pathway has been gained by fluorescence-based intracellular Ca(2+) measurements because of its convenience and feasibility for high-throughput screening. The objective of this report is to summarize a few fluorescence-based methods to measure the activation of SOCE in monolayer cells, suspended cells and muscle fibers. The most commonly used of these fluorescence methods is to directly monitor the dynamics of intracellular Ca(2+) using the ratio of F(340nm;) and F(380nm;) (510 nm for emission wavelength) of the ratiometric Ca(2+) indicator Fura-2. To isolate the activity of unidirectional SOCE from intracellular Ca(2+) release and Ca(2+) extrusion, a Mn(2+) quenching assay is frequently used. Mn(2+) is known to be able to permeate into cells via SOCE while it is impervious to the surface membrane extrusion processes or to ER uptake by Ca(2+) pumps due to its very high affinity with Fura-2. As a result, the quenching of Fura-2 fluorescence induced by the entry of extracellular Mn(2+) into the cells represents a measurement of activity of SOCE. Ratiometric measurement and the Mn(+2) quenching assays can be performed on a