Science.gov

Sample records for action potential amplitude

  1. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases.

    PubMed

    Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin

    2014-07-15

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

  2. [Multimodality in the amplitude distribution of miniature endplate potentials due to the action of spatially discrete areas of transmitter release].

    PubMed

    Zefirov, A L

    1983-05-01

    Miniature end plate potentials (MEPPs) were simultaneously recorded in frog sartorius muscle by two intracellular microelectrodes. Some isolated groups of points (clouds) were found on the diagram of MEPPs scatter. Several peaks each of which was composed of signals from certain clouds (or from several clouds) on the scatter diagram were found on the histograms of MEPPs amplitude distribution. It is assumed that the clouds on the scatter histogram and the peaks on the histogram of MEPPs amplitudes are formed at the cost of secretion of quantum acetylcholine from spatial separate areas of transmitter release. The data obtained do not correspond with the subquantum hypothesis of transmitter release in neuromuscular junctions.

  3. Early Afterdepolarizations with Growing Amplitudes via Delayed Subcritical Hopf Bifurcations and Unstable Manifolds of Saddle Foci in Cardiac Action Potential Dynamics

    PubMed Central

    Kügler, Philipp

    2016-01-01

    Early afterdepolarizations (EADs) are pathological oscillations in cardiac action potentials during the repolarization phase and may be caused by drug side effects, ion channel disease or oxidative stress. The most widely observed EAD pattern is characterized by oscillations with growing amplitudes. So far, its occurence has been explained in terms of a supercritical Hopf bifurcation in the fast subsystem of the action potential dynamics from which stable limit cycles with growing amplitudes emerge. The novel contribution of this article is the introduction of two alternative explanations of EAD genesis with growing amplitudes that do not involve stable limit cycles in fast subsystems. In particular, we demonstrate that EAD patterns with growing amplitudes may alternatively arise due to a delayed subcritical Hopf bifurcation or an unstable manifold of a saddle focus fixed point in the full fast-slow system modelling the action potential. Our work extends the list of possible dynamical EAD mechanisms and may contribute to a classification of drug effects in preclinical cardiotoxicity testing. PMID:26977805

  4. Early Afterdepolarizations with Growing Amplitudes via Delayed Subcritical Hopf Bifurcations and Unstable Manifolds of Saddle Foci in Cardiac Action Potential Dynamics.

    PubMed

    Kügler, Philipp

    2016-01-01

    Early afterdepolarizations (EADs) are pathological oscillations in cardiac action potentials during the repolarization phase and may be caused by drug side effects, ion channel disease or oxidative stress. The most widely observed EAD pattern is characterized by oscillations with growing amplitudes. So far, its occurence has been explained in terms of a supercritical Hopf bifurcation in the fast subsystem of the action potential dynamics from which stable limit cycles with growing amplitudes emerge. The novel contribution of this article is the introduction of two alternative explanations of EAD genesis with growing amplitudes that do not involve stable limit cycles in fast subsystems. In particular, we demonstrate that EAD patterns with growing amplitudes may alternatively arise due to a delayed subcritical Hopf bifurcation or an unstable manifold of a saddle focus fixed point in the full fast-slow system modelling the action potential. Our work extends the list of possible dynamical EAD mechanisms and may contribute to a classification of drug effects in preclinical cardiotoxicity testing.

  5. Cardiac action potential imaging

    NASA Astrophysics Data System (ADS)

    Tian, Qinghai; Lipp, Peter; Kaestner, Lars

    2013-06-01

    Action potentials in cardiac myocytes have durations in the order of magnitude of 100 milliseconds. In biomedical investigations the documentation of the occurrence of action potentials is often not sufficient, but a recording of the shape of an action potential allows a functional estimation of several molecular players. Therefore a temporal resolution of around 500 images per second is compulsory. In the past such measurements have been performed with photometric approaches limiting the measurement to one cell at a time. In contrast, imaging allows reading out several cells at a time with additional spatial information. Recent developments in camera technologies allow the acquisition with the required speed and sensitivity. We performed action potential imaging on isolated adult cardiomyocytes of guinea pigs utilizing the fluorescent membrane potential sensor di-8-ANEPPS and latest electron-multiplication CCD as well as scientific CMOS cameras of several manufacturers. Furthermore, we characterized the signal to noise ratio of action potential signals of varying sets of cameras, dye concentrations and objective lenses. We ensured that di-8-ANEPPS itself did not alter action potentials by avoiding concentrations above 5 μM. Based on these results we can conclude that imaging is a reliable method to read out action potentials. Compared to conventional current-clamp experiments, this optical approach allows a much higher throughput and due to its contact free concept leaving the cell to a much higher degree undisturbed. Action potential imaging based on isolated adult cardiomyocytes can be utilized in pharmacological cardiac safety screens bearing numerous advantages over approaches based on heterologous expression of hERG channels in cell lines.

  6. Mechanomyographic amplitude and frequency responses during dynamic muscle actions: a comprehensive review

    PubMed Central

    Beck, Travis W; Housh, Terry J; Cramer, Joel T; Weir, Joseph P; Johnson, Glen O; Coburn, Jared W; Malek, Moh H; Mielke, Michelle

    2005-01-01

    The purpose of this review is to examine the literature that has investigated mechanomyographic (MMG) amplitude and frequency responses during dynamic muscle actions. To date, the majority of MMG research has focused on isometric muscle actions. Recent studies, however, have examined the MMG time and/or frequency domain responses during various types of dynamic activities, including dynamic constant external resistance (DCER) and isokinetic muscle actions, as well as cycle ergometry. Despite the potential influences of factors such as changes in muscle length and the thickness of the tissue between the muscle and the MMG sensor, there is convincing evidence that during dynamic muscle actions, the MMG signal provides valid information regarding muscle function. This argument is supported by consistencies in the MMG literature, such as the close relationship between MMG amplitude and power output and a linear increase in MMG amplitude with concentric torque production. There are still many issues, however, that have yet to be resolved, and the literature base for MMG during both dynamic and isometric muscle actions is far from complete. Thus, it is important to investigate the unique applications of MMG amplitude and frequency responses with different experimental designs/methodologies to continually reassess the uses/limitations of MMG. PMID:16364182

  7. Scattering amplitudes for multi-indexed extensions of solvable potentials

    SciTech Connect

    Ho, C.-L.; Lee, J.-C.; Sasaki, R.

    2014-04-15

    New solvable one-dimensional quantum mechanical scattering problems are presented. They are obtained from known solvable potentials by multiple Darboux transformations in terms of virtual and pseudo virtual wavefunctions. The same method applied to confining potentials, e.g.  Pöschl–Teller and the radial oscillator potentials, has generated the multi-indexed Jacobi and Laguerre polynomials. Simple multi-indexed formulas are derived for the transmission and reflection amplitudes of several solvable potentials. -- Highlights: •Scattering amplitudes calculated for infinitely many new solvable potentials. •New scattering potentials obtained by deforming six known solvable potentials. •Multiple Darboux transformations in terms of (pseudo) virtual states employed. •Scattering amplitudes checked to obey the shape invariance relation. •Errors in scattering amplitudes of some undeformed potentials in the literature corrected.

  8. Action potential in charophytes.

    PubMed

    Beilby, Mary Jane

    2007-01-01

    The plant action potential (AP) has been studied for more than half a century. The experimental system was provided mainly by the large charophyte cells, which allowed insertion of early large electrodes, manipulation of cell compartments, and inside and outside media. These early experiments were inspired by the Hodgkin and Huxley (HH) work on the squid axon and its voltage clamp techniques. Later, the patch clamping technique provided information about the ion transporters underlying the excitation transient. The initial models were also influenced by the HH picture of the animal AP. At the turn of the century, the paradigm of the charophyte AP shifted to include several chemical reactions, second messenger-activated channel, and calcium ion liberation from internal stores. Many aspects of this new model await further clarification. The role of the AP in plant movements, wound signaling, and turgor regulation is now well documented. Involvement in invasion by pathogens, chilling injury, light, and gravity sensing are under investigation.

  9. Characteristics of cardiac action potentials in marsupials.

    PubMed

    Campbell, T J

    1989-01-01

    Standard microelectrode techniques were used to record action potentials from single atrial, ventricular and Purkinje fibers of hearts taken from three species of marsupial (Macropus rufus, Macropus robustus and Macropus eugenii) and from dogs, sheep and guinea-pigs. The major electrophysiological parameters of marsupial potentials were qualitatively similar to the values for placental mammals. The grouped data for ventricular action potentials from studies on 6 adult male red kangaroos (Macropus rufus) were (mean +/- SD): Resting potential -69.5 +/- 5.0 mV; action potential amplitude 92.7 +/- 5.7 mV; action potential duration (to 90% repolarization): 182.5 +/- 17.5 ms; maximum rate of depolarization: 196.5 +/- 80.1 V/s. The major point of difference was the short duration of the red kangaroo ventricular action potential compared to those of the placental mammals, and compared to atrial cells from the kangaroos. It is suggested that this explains the short QT interval reported by others for kangaroo electrocardiograms, and that it may also be implicated in the high frequency of sudden death previously noted in these animals.

  10. Scattering amplitudes for the rationally extended PT symmetric complex potentials

    NASA Astrophysics Data System (ADS)

    Kumari, Nisha; Yadav, Rajesh Kumar; Khare, Avinash; Bagchi, Bijan; Mandal, Bhabani Prasad

    2016-10-01

    In this paper, we consider the rational extensions of two different classes of PT symmetric complex potentials namely the asymptotically vanishing Scarf II and asymptotically non-vanishing Rosen-Morse II [ RM-II] and obtain the accompanying bound state eigenfunctions in terms of the exceptional Xm Jacobi polynomials and a certain class of orthogonal polynomials. By considering the asymptotic behavior of the exceptional polynomials, we also derive the reflection and transmission amplitudes for them and discuss the various novel properties of the corresponding amplitudes.

  11. K+-nucleus potentials from K+-nucleon amplitudes

    NASA Astrophysics Data System (ADS)

    Friedman, E.

    2016-10-01

    Optical potentials for K+-nucleus interactions are constructed from K+-nucleon amplitudes using recently developed algorithm based on K+-N kinematics in the nuclear medium. With the deep penetration of K+ mesons into the nucleus at momenta below 800 MeV / c it is possible to test this approach with greater sensitivity than hitherto done with K- and pions. The energy-dependence of experimental reaction and total cross sections on nuclei is better reproduced with this approach compared to fixed-energy amplitudes. The inclusion of Pauli correlations in the medium also improves the agreement between calculation and experiment. The absolute scale of the cross sections is reproduced very well for 6Li but for C, Si and Ca calculated cross sections are (23 ± 4)% smaller than experiment, in agreement with earlier analyses. Two phenomenological models that produce such missing strength suggest that the imaginary part of the potential needs about 40% enhancement.

  12. Shockwave-induced compound action potentials in the peripheral nerve.

    PubMed

    Wehner, H D; Sellier, K

    1981-01-01

    To verify a presumed interaction between shockwaves arisen by impacts of high velocity projectiles and nervous tissue an electrophysiological experiment is performed with the following results: In peripheral nerves regular compound action potentials (CAPs) are provoked by shockwaves the amplitudes of which are increased corresponding to the pressure intensity of the shockwaves. The nerve shows no electrical activity below a certain pressure threshold (0.75 bar). Saturation of the CAP amplitude occurs beyond a pressure limit of 8 bar.

  13. [Potential reversal/amplitude analysis: problems of normal value determination].

    PubMed

    Finsterer, J; Mamoli, B

    1991-09-01

    Turn/amplitude-analysis was applied to the right m. biceps brachii and the right m. rectus femoris of 30 healthy women aged 19 to 39 years. Interference patterns were recorded at 20, 40 and 60% of the individual maximum force of both muscles. We evaluated the turns/s, the amplitude/turn and the ratios amplitude/turns:turns/s and turns/s:amplitude/turn. Normal values of the turn/amplitude-parameter were calculated as means +/- 2 SD at defined levels of force (table 1 and fig. 2) and in form of clouds (fig. 3). Our clouds were clearly different from those of Stalberg. Since normal values of our and other studies were inconsistent we believe that every laboratory has to elaborate its own normal values. Turns/s, amplitude/turn and the ratio turns/s:amplitude/turn increased and the ratio amplitude/turns/s decreased with increasing force (fig. 6 and 7). Turn/amplitude-parameters were partly significantly higher or lower in the m. biceps brachii than in the m. rectus femoris (fig. 8.).

  14. The characteristics of action potentials in primo vessels and the effects of acetylcholine injection to the action potentials.

    PubMed

    Cho, Seong Jin; Lim, Jaekwan; Yeon, Sun Hee; Kwon, O Sang; Choi, Kwang-Ho; Choi, Sun-Mi; Ryu, Yeon-Hee

    2013-01-01

    In a previous study, we found that Primo vessels generate different action potentials in smooth muscles, but this study compared the pulse shape to distinguish the two tissues. Thus, a more sophisticated extracellular experiment was performed in this study using an acetylcholine injection; we then observed changes in the amplitude, FWHM (full width at half maximum), and period to explore Primo vessel function. A third type of pulse was recorded for Primo vessels. We observed fast depolarizing and repolarizing phases for this pulse. Further, its FWHM was 30 ms between smooth muscles and neurons. Acetylcholine affected only the period. The amplitude and FWHM were consistent after injection. Primo-vessels generated action potentials at twice the frequency after injection. From the results, we speculate that Primo-vessels perform a role in transferring signals in a different manner, which may be relevant for acupuncture treatment.

  15. Quadratic adaptive algorithm for solving cardiac action potential models.

    PubMed

    Chen, Min-Hung; Chen, Po-Yuan; Luo, Ching-Hsing

    2016-10-01

    An adaptive integration method is proposed for computing cardiac action potential models accurately and efficiently. Time steps are adaptively chosen by solving a quadratic formula involving the first and second derivatives of the membrane action potential. To improve the numerical accuracy, we devise an extremum-locator (el) function to predict the local extremum when approaching the peak amplitude of the action potential. In addition, the time step restriction (tsr) technique is designed to limit the increase in time steps, and thus prevent the membrane potential from changing abruptly. The performance of the proposed method is tested using the Luo-Rudy phase 1 (LR1), dynamic (LR2), and human O'Hara-Rudy dynamic (ORd) ventricular action potential models, and the Courtemanche atrial model incorporating a Markov sodium channel model. Numerical experiments demonstrate that the action potential generated using the proposed method is more accurate than that using the traditional Hybrid method, especially near the peak region. The traditional Hybrid method may choose large time steps near to the peak region, and sometimes causes the action potential to become distorted. In contrast, the proposed new method chooses very fine time steps in the peak region, but large time steps in the smooth region, and the profiles are smoother and closer to the reference solution. In the test on the stiff Markov ionic channel model, the Hybrid blows up if the allowable time step is set to be greater than 0.1ms. In contrast, our method can adjust the time step size automatically, and is stable. Overall, the proposed method is more accurate than and as efficient as the traditional Hybrid method, especially for the human ORd model. The proposed method shows improvement for action potentials with a non-smooth morphology, and it needs further investigation to determine whether the method is helpful during propagation of the action potential. PMID:27639239

  16. A physical action potential generator: design, implementation and evaluation

    PubMed Central

    Latorre, Malcolm A.; Chan, Adrian D. C.; Wårdell, Karin

    2015-01-01

    The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1–40 in incremental steps of 1) and the node drive potential (0–2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems. PMID:26539072

  17. Effect of a prenylamine analog (MG8926) on spontaneous action potentials in isolated rabbit sinoatrial node.

    PubMed

    Nakanishi, H; Matsuoka, I; Ono, T; Yoshida, H; Uchibori, T; Kogi, K

    1996-12-01

    Effects of verapamil, prenylamine and a prenylamine analog, MG8926 on the intracellular spontaneous action potentials recorded from the isolated rabbit sinoatrial (SA) node were studied. Verapamil (1 microM), a selective inhibitor for slow Ca2+ channels, prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential, the amplitude of action potential and the maximal diastolic potential, and usually arrested showing subthreshold fluctuation of the membrane potential within several ten min. Prenylamine (10 microM), a nonselective inhibitor for slow Ca2+ channels, tended to prolong the cycle length to decrease the diastolic depolarization, the rate of rise of action potential, the amplitude of action potential. However, these changes were statistically insignificant. Prenylamine at the concentration of 10 microM had no effect on the maximal diastolic potential. MG8926 (10 microM) prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential and tended to decrease the amplitude of action potential. MG8926 at the concentration of 10 microM had almost no effect on the maximal diastolic potential. The present findings may indicate that replacement of phenyl residue of prenylamine by cyclohexyl residue increases the inhibitory action on the slow Ca2+ channels in rabbit SA node.

  18. The origin of the skewed amplitude distribution of spontaneous excitatory junction potentials in poorly coupled smooth muscle cells

    PubMed Central

    Young, J.S.; Brain, K.L.; Cunnane, T.C.

    2007-01-01

    The skewed amplitude distribution of spontaneous excitatory junction potentials (sEJPs) in the mouse vas deferens and other electrically-coupled smooth muscle syncytia has been attributed to electrically-attenuated depolarizations resulting from the spontaneous release of quantized packets of ATP acting on remote smooth muscle cells (SMCs). However, in the present investigation surface SMCs of the mouse isolated vas deferens were poorly electrically coupled, with input resistances (176±18 MΩ, range: 141–221 MΩ, n=4) similar to those of dissociated cells. Furthermore, the amplitude of evoked EJPs was more variable in surface compared with deeper SMCs (F test, F=17.4, P<0.0001). Using simultaneous electrophysiology and confocal microscopy to investigate these poorly-coupled cells, it is shown that α-latrotoxin-stimulated sEJPs correlate, in timing (median delay ranged from −30 to −57 ms, P<0.05 in all experiments, n=5) and amplitude (Pearson product moment correlation, ρ>0.55 and P<0.001), with purinergic neuroeffector Ca2+ transients (NCTs) in SMCs. The temporal correlation between sEJPs of widely ranging amplitude with NCTs in the impaled SMC demonstrates that all sEJPs could arise from neurotransmitter action on the impaled cell and that the skewed distribution of sEJPs can be explained by the variable effect of packets of ATP on a single SMC. The amplitude correlation of sEJPs and NCTs argues against the attenuation of electrical signal amplitude along the length of a single SMC. The skewed sEJP amplitude distribution arising from neurotransmitter release on single SMCs is consistent with a broad neurotransmitter packet size distribution at sympathetic neuroeffector junctions. PMID:17208381

  19. Effects of troglitazone and pioglitazone on the action potentials and membrane currents of rabbit ventricular myocytes.

    PubMed

    Ikeda, S; Watanabe, T

    1998-09-18

    The effects of the antidiabetic thiazolidinediones troglitazone and pioglitazone on action potentials and membrane currents were studied in rabbit ventricular myocytes. Troglitazone (10 microM) reversibly reduced excitability of the myocytes and modified their action potential configuration. It significantly increased the stimulation threshold required to elicit action potentials and decreased action potential amplitude and the maximum upstroke velocity of the action potentials. The Inhibition of the maximum upstroke velocity by troglitazone was also significant at 1 microM. Voltage-clamp experiments revealed that troglitazone (10 microM) reversibly inhibited both the slow inward Ca2+ current and the steady-state K+ current. In contrast to troglitazone, pioglitazone (1-10 microM) had no significant effect on the excitability, action potential configuration, or membrane currents of myocytes. These results suggest that troglitazone, but not pioglitazone, modulates Na+, Ca2+ and K+ currents, leading to the changes in excitability and action potential configuration of ventricular myocytes. PMID:9797043

  20. Correlation of action potentials in adjacent neurons

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2015-12-01

    A possible mechanism for the synchronization of action potential propagation along a bundle of neurons (ephaptic coupling) is considered. It is shown that this mechanism is similar to the salutatory conduction of the action potential between the nodes of Ranvier in myelinated axons. The proposed model allows us to estimate the scale of the correlation, i.e., the distance between neurons in the nervous tissue, wherein their synchronization becomes possible. The possibility for experimental verification of the proposed model of synchronization is discussed.

  1. Screening Action Potentials: The Power of Light

    PubMed Central

    Kaestner, Lars; Lipp, Peter

    2011-01-01

    Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated read out and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for, e.g., pharmacological screens the following preparatory work has to be provided: (i) model cells under investigation need to represent target cells in the best possible manner; (ii) optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable read out with minimal interaction with the naive behavior of the cells and (iii) devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials. PMID:21847381

  2. Electrotonic and action potentials in the Venus flytrap.

    PubMed

    Volkov, Alexander G; Vilfranc, Chrystelle L; Murphy, Veronica A; Mitchell, Colee M; Volkova, Maia I; O'Neal, Lawrence; Markin, Vladislav S

    2013-06-15

    The electrical phenomena and morphing structures in the Venus flytrap have attracted researchers since the nineteenth century. We have observed that mechanical stimulation of trigger hairs on the lobes of the Venus flytrap induces electrotonic potentials in the lower leaf. Electrostimulation of electrical circuits in the Venus flytrap can induce electrotonic potentials propagating along the upper and lower leaves. The instantaneous increase or decrease in voltage of stimulating potential generates a nonlinear electrical response in plant tissues. Any electrostimulation that is not instantaneous, such as sinusoidal or triangular functions, results in linear responses in the form of small electrotonic potentials. The amplitude and sign of electrotonic potentials depend on the polarity and the amplitude of the applied voltage. Electrical stimulation of the lower leaf induces electrical signals, which resemble action potentials, in the trap between the lobes and the midrib. The trap closes if the stimulating voltage is above the threshold level of 4.4V. Electrical responses in the Venus flytrap were analyzed and reproduced in the discrete electrical circuit. The information gained from this study can be used to elucidate the coupling of intracellular and intercellular communications in the form of electrical signals within plants.

  3. Introducing the Action Potential to Psychology Students

    ERIC Educational Resources Information Center

    Simon-Dack, Stephanie L.

    2014-01-01

    For this simple active learning technique for teaching, students are assigned "roles" and act out the process of the action potential (AP), including the firing threshold, ion-specific channels for ions to enter and leave the cell, diffusion, and the refractory period. Pre-post test results indicated that students demonstrated increased…

  4. Non-relativistic scattering amplitude for a new multi-parameter exponential-type potential

    NASA Astrophysics Data System (ADS)

    Yazarloo, B. H.; Mehraban, H.; Hassanabadi, H.

    2016-08-01

    In this paper, we study the scattering properties of s-wave Schrödinger equation for the multi-parameter potential, which can be reduced into four special cases for different values of potential parameters, i.e., Hulthén, Manning–Rosen, and Eckart potentials. We also obtain and investigate the scattering amplitudes of these special cases. Some numerical results are also obtained and reported.

  5. Non-relativistic scattering amplitude for a new multi-parameter exponential-type potential

    NASA Astrophysics Data System (ADS)

    Yazarloo, B. H.; Mehraban, H.; Hassanabadi, H.

    2016-08-01

    In this paper, we study the scattering properties of s-wave Schrödinger equation for the multi-parameter potential, which can be reduced into four special cases for different values of potential parameters, i.e., Hulthén, Manning-Rosen, and Eckart potentials. We also obtain and investigate the scattering amplitudes of these special cases. Some numerical results are also obtained and reported.

  6. The action potential of Dionaea muscipula Ellis.

    PubMed

    Hodick, D; Sievers, A

    1988-04-01

    The intention of this investigation was to acquire more concise information about the nature of the action potential of Dionaea muscipula Ellis and the different types of cells generating and conducting it. It is shown by microelectrode measurements that, besides the sensory cells, all the major tissues of the trap lobes are excitable, firing action potentials with pronounced after-hyperpolarizations. The action potentials are strictly dependent on Ca(2+). Their peak depolarizations are shifted 25-27 mV in a positive direction after a tenfold increase in external Ca(2+) concentration. Perfusions with 1 mM ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or 1 mM LaCl3 completely inhibit excitability. Magnesium ions only slightly affect the peak depolarizations but considerably prolong action potentials. Sodium azide and 2,4-dinitrophenol also abolish excitation, probably by reducing the intracellular ATP concentration. Furthermore, it is tested whether the sensory cells can be distinguished from the other cells of the trap by their electrical behaviour. The resting potentials of sensory cells (-161±7 mV) and mesophyll cells (-155±8 mV) are of the same magnitude. Changes in external ion concentrations affect resting and action potentials in both cell types in a similar way. Additional freeze-fracture studies of both cell types reveal similar numbers and distributions of intramembrane particles on the fracture faces of the plasma membrane, which is most likely the mechanosensor. These findings stress the view that the high mechanosensitivity of the sensory hair results from its anatomy and not from a specialized perception mechanism. It is proposed that trap closure is triggered by a rise in the cytoplasmic concentration of Ca(2+) or a Ca(2+)-activated regulatory complex, which must exceed a threshold concentration. Since the Ca(2+) influx during a single action potential does not suffice to reach this threshold, at least two stimulations

  7. Mechanical surface waves accompany action potential propagation.

    PubMed

    El Hady, Ahmed; Machta, Benjamin B

    2015-01-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs. PMID:25819404

  8. Mechanical surface waves accompany action potential propagation

    NASA Astrophysics Data System (ADS)

    El Hady, Ahmed; Machta, Benjamin B.

    2015-03-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs.

  9. Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

    PubMed Central

    Yu, Yuguo; Hill, Adam P.; McCormick, David A.

    2012-01-01

    The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na+ channel inactivation, resulting in a marked reduction in overlap of the inward Na+, and outward K+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37–42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code. PMID:22511855

  10. Are the amplitudes of visual evoked potentials sensitive indices of hangover effects after repeated doses of benzodiazepines?

    PubMed

    Kulikowski, J J; McGlone, F F; Kranda, K; Ott, H

    1984-01-01

    Here we compared the efficacy of two electrophysiological techniques in detecting hangover effects after repeated administration (five days) of benzodiazepines. Twelve hours after the last ingestion, possible effects on evoked potentials (EPs) of the long- and short-acting benzodiazepines, flurazepam and lormetazepam, were compared here with those of placebo under a double-blind experimental condition. The EPs were recorded from occipital and parietal sites during an active discrimination of two amoeboid shapes and passive viewing of sine-wave grating patterns turned on and off. In the former task, the subject was requested to make a selective response with respect to whether the two shapes appeared the same or different and his reaction times were simultaneously recorded. Neither benzodiazepine influenced the latencies of any of the sensory and late EP components. Flurazepam's long-acting metabolite, N-desalkylflurazepam, reduced the amplitudes of all the EP components suggesting a somewhat general mode of action. This was not the case for lormetazepam. N-desalkylflurazepam reduced the amplitudes of the occipital visual evoked potentials (VEPs) to sine-wave gratings to a greater extent than the amplitudes of the late parietal EPs to amoeboid shapes. This effect did not show any particular preference for either of the subsystems processing pattern and movement information. The amplitudes of the late EP components, such as N200 and P300 waves recorded from parietal sites, were reduced considerably more after flurazepam administration than their counterparts recorded from the occiput. This observation points to the possible existence of at least two separate sources of the N200-P300 complex with different affinities to the N-desalkylflurazepam. The flurazepam-induced amplitude reduction observed for VEPs to gratings may reflect an attenuation in the detectability of both pattern and movement. The attenuation of the late EP amplitudes is possibly a function of several

  11. Calculation of K →π π decay amplitudes with improved Wilson fermion action in lattice QCD

    NASA Astrophysics Data System (ADS)

    Ishizuka, N.; Ishikawa, K.-I.; Ukawa, A.; Yoshié, T.

    2015-10-01

    We present our result for the K →π π decay amplitudes for both the Δ I =1 /2 and 3 /2 processes with the improved Wilson fermion action. Expanding on the earlier works by Bernard et al. and by Donini et al., we show that mixings with four-fermion operators with wrong chirality are absent even for the Wilson fermion action for the parity odd process in both channels due to CPS symmetry. Therefore, after subtraction of an effect from the lower dimensional operator, a calculation of the decay amplitudes is possible without complications from operators with wrong chirality, as for the case with chirally symmetric lattice actions. As a first step to verify the possibility of calculations with the Wilson fermion action, we consider the decay amplitudes at an unphysical quark mass mK˜2 mπ . Our calculations are carried out with Nf=2 +1 gauge configurations generated with the Iwasaki gauge action and nonperturbatively O (a )-improved Wilson fermion action at a =0.091 fm , mπ=280 MeV , and mK=580 MeV on a 323×64 (L a =2.9 fm ) lattice. For the quark loops in the penguin and disconnected contributions in the I =0 channel, the combined hopping parameter expansion and truncated solver method work very well for variance reduction. We obtain, for the first time with a Wilson-type fermion action, that Re A0=60 (36 )×1 0-8 GeV and Im A0=-67 (56 )×1 0-12 GeV for a matching scale q*=1 /a . The dependence on the matching scale q* for these values is weak.

  12. Modulation of amplitude and latency of motor evoked potential by direction of transcranial magnetic stimulation

    NASA Astrophysics Data System (ADS)

    Sato, Aya; Torii, Tetsuya; Iwahashi, Masakuni; Itoh, Yuji; Iramina, Keiji

    2014-05-01

    The present study analyzed the effects of monophasic magnetic stimulation to the motor cortex. The effects of magnetic stimulation were evaluated by analyzing the motor evoked potentials (MEPs). The amplitude and latency of MEPs on the abductor pollicis brevis muscle were used to evaluate the effects of repetitive magnetic stimulation. A figure eight-shaped flat coil was used to stimulate the region over the primary motor cortex. The intensity of magnetic stimulation was 120% of the resting motor threshold, and the frequency of magnetic stimulation was 0.1 Hz. In addition, the direction of the current in the brain was posterior-anterior (PA) or anterior-posterior (AP). The latency of MEP was compared with PA and AP on initial magnetic stimulation. The results demonstrated that a stimulus in the AP direction increased the latency of the MEP by approximately 2.5 ms. MEP amplitude was also compared with PA and AP during 60 magnetic stimulations. The results showed that a stimulus in the PA direction gradually increased the amplitude of the MEP. However, a stimulus in the AP direction did not modulate the MEP amplitude. The average MEP amplitude induced from every 10 magnetic pulses was normalized by the average amplitude of the first 10 stimuli. These results demonstrated that the normalized MEP amplitude increased up to approximately 150%. In terms of pyramidal neuron indirect waves (I waves), magnetic stimulation inducing current flowing backward to the anterior preferentially elicited an I1 wave, and current flowing forward to the posterior elicited an I3 wave. It has been reported that the latency of the I3 wave is approximately 2.5 ms longer than the I1 wave elicitation, so the resulting difference in latency may be caused by this phenomenon. It has also been reported that there is no alteration of MEP amplitude at a frequency of 0.1 Hz. However, this study suggested that the modulation of MEP amplitude depends on stimulation strength and stimulation direction.

  13. Ca channel gating during cardiac action potentials.

    PubMed

    Mazzanti, M; DeFelice, L J

    1990-10-01

    How do Ca channels conduct Ca ions during the cardiac action potential? We attempt to answer this question by applying a two-microelectrode technique, previously used for Na and K currents, in which we record the patch current and the action potential at the same time (Mazzanti, M., and L. J. DeFelice. 1987. Biophys. J. 12:95-100, and 1988. Biophys. J. 54:1139-1148; Wellis, D., L. J. DeFelice, and M. Mazzanti. 1990. Biophys. J. 57:41-48). In this paper, we also compare the action currents obtained by the technique with the step-protocol currents obtained during standard voltage-clamp experiments. Individual Ca channels were measured in 10 mM Ca/1 Ba and 10 mM Ba. To describe part of our results, we use the nomenclature introduced by Hess, P., J. B. Lansman, and R. W. Tsien (1984. Nature (Lond.). 311:538-544). With Ba as the charge carrier, Ca channel kinetics convert rapidly from long to short open times as the patch voltage changes from 20 to -20 mV. This voltage-dependent conversion occurs during action potentials and in step-protocol experiments. With Ca as the charge carrier, the currents are brief at all voltages, and it is difficult to define either the number of channels in the patch or the conductance of the individual channels. Occasionally, however, Ca-conducting channels spontaneously convert to long-open-time kinetics (in Hess et al., 1984, notation, mode 2). When this happens, which is about once in every 100beats, there usually appears to be only one channel in the patch. In this rare configuration, the channel is open long enough to measure its conductance in 10 Ca/ 1 Ba. The value is 8-10 pS, which is about half the conductance in Ba. Because the long openings occur so infrequently with Ca as the charge carrier, they contribute negligibly to the average Ca current at any particular time during an action potential. However, the total number of Ca ions entering during these long openings may be significant when compared to the number entering by the

  14. Ca channel gating during cardiac action potentials.

    PubMed

    Mazzanti, M; DeFelice, L J

    1990-10-01

    How do Ca channels conduct Ca ions during the cardiac action potential? We attempt to answer this question by applying a two-microelectrode technique, previously used for Na and K currents, in which we record the patch current and the action potential at the same time (Mazzanti, M., and L. J. DeFelice. 1987. Biophys. J. 12:95-100, and 1988. Biophys. J. 54:1139-1148; Wellis, D., L. J. DeFelice, and M. Mazzanti. 1990. Biophys. J. 57:41-48). In this paper, we also compare the action currents obtained by the technique with the step-protocol currents obtained during standard voltage-clamp experiments. Individual Ca channels were measured in 10 mM Ca/1 Ba and 10 mM Ba. To describe part of our results, we use the nomenclature introduced by Hess, P., J. B. Lansman, and R. W. Tsien (1984. Nature (Lond.). 311:538-544). With Ba as the charge carrier, Ca channel kinetics convert rapidly from long to short open times as the patch voltage changes from 20 to -20 mV. This voltage-dependent conversion occurs during action potentials and in step-protocol experiments. With Ca as the charge carrier, the currents are brief at all voltages, and it is difficult to define either the number of channels in the patch or the conductance of the individual channels. Occasionally, however, Ca-conducting channels spontaneously convert to long-open-time kinetics (in Hess et al., 1984, notation, mode 2). When this happens, which is about once in every 100beats, there usually appears to be only one channel in the patch. In this rare configuration, the channel is open long enough to measure its conductance in 10 Ca/ 1 Ba. The value is 8-10 pS, which is about half the conductance in Ba. Because the long openings occur so infrequently with Ca as the charge carrier, they contribute negligibly to the average Ca current at any particular time during an action potential. However, the total number of Ca ions entering during these long openings may be significant when compared to the number entering by the

  15. Ionic requirements for arterial action potential

    PubMed Central

    Keatinge, W. R.

    1968-01-01

    1. Strips of smooth muscle from common carotid arteries of sheep were electrically quiescent in solution containing Na 148 mM and Ca 2·5 mM. 2. When Ca was removed they became electrically active. Addition of low concentrations of Ca (0·025-0·075 mM) or Mg (0·025-0·750 mM) stopped their activity while ethylenediamine tetra-acetate (EDTA) (1·25 mM) accelerated it. 3. Replacement of Na by Tris or choline stopped the activity in Ca-free solution. After partial replacement of Na electrical activity could be restored by lowering the resting potential but after complete replacement of Na it could not. 4. In the presence of Ca (2·5 mM) small spikes could sometimes be induced after 20 min in Na-free Tris solution by lowering the resting potential by an increase in the external K concentration. 5. The results indicate that the depolarizing current of action potentials in this smooth muscle was largely carried by Na, although a little may have been carried by Ca in Ca-containing solutions. 6. The arteries in general resembled striated muscle rather than intestinal smooth muscle in these respects, but unlike striated muscle their action potentials were not stopped by tetrodotoxin. ImagesFig. 2 PMID:5639765

  16. A phantom axon setup for validating models of action potential recordings.

    PubMed

    Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

  17. A phantom axon setup for validating models of action potential recordings.

    PubMed

    Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %. PMID:27016364

  18. Two-pion exchange potential and the {pi}N amplitude

    SciTech Connect

    M. T. Pena; Franz Gross; Yohanes Surya

    1996-05-01

    The authors discuss the two-pion exchange potential which emerges from a box diagram with one nucleon (the spectator) restricted to its mass shell, and the other nucleon line replaced by a subtracted, covariant {pi}N scattering amplitude which includes {Delta}, Roper, and D{sub 13} isobars, as well as contact terms and off-shell (non-pole) dressed nucleon terms. The {pi}N amplitude satisfies chiral symmetry constraints and fits {pi}N data below {approximately} 700 MeV pion energy. They find that this TPE potential can be well approximated by the exchange of an effective sigma and delta meson, with parameters close to the ones used in one-boson-exchange models that fit NN data below the pion production threshold.

  19. Effect of mechanical tactile noise on amplitude of visual evoked potentials: multisensory stochastic resonance.

    PubMed

    Méndez-Balbuena, Ignacio; Huidobro, Nayeli; Silva, Mayte; Flores, Amira; Trenado, Carlos; Quintanar, Luis; Arias-Carrión, Oscar; Kristeva, Rumyana; Manjarrez, Elias

    2015-10-01

    The present investigation documents the electrophysiological occurrence of multisensory stochastic resonance in the human visual pathway elicited by tactile noise. We define multisensory stochastic resonance of brain evoked potentials as the phenomenon in which an intermediate level of input noise of one sensory modality enhances the brain evoked response of another sensory modality. Here we examined this phenomenon in visual evoked potentials (VEPs) modulated by the addition of tactile noise. Specifically, we examined whether a particular level of mechanical Gaussian noise applied to the index finger can improve the amplitude of the VEP. We compared the amplitude of the positive P100 VEP component between zero noise (ZN), optimal noise (ON), and high mechanical noise (HN). The data disclosed an inverted U-like graph for all the subjects, thus demonstrating the occurrence of a multisensory stochastic resonance in the P100 VEP.

  20. Sagdeev potential approach for large amplitude compressional Alfvenic double layers in viscous plasmas

    SciTech Connect

    Panwar, Anuraj; Rizvi, H.; Ryu, C. M.

    2013-11-15

    Sagdeev’s technique is used to study the large amplitude compressional Alfvenic double layers in a magnetohydrodynamic plasma taking into account the small plasma β and small values of kinematic viscosity. Dispersive effect raised by non-ideal electron inertia currents perpendicular to the ambient magnetic field. The range of allowed values of the soliton speed, M (Mach number), plasma β (ratio of the plasma thermal pressure to the pressure in the confining magnetic field), and viscosity coefficient, wherein double layer may exist, are determined. In the absence of collisions, viscous dissipation modifies the Sagdeev potential and results in large amplitude compressional Alfvenic double layers. The depth of Sagdeev potential increases with the increasing Mach number and plasma β, however, decreases with the increasing viscosity. The double layer structure increases with the increasing plasma β, but decreases with increasing viscous dissipation μ(tilde sign)

  1. Effect of mechanical tactile noise on amplitude of visual evoked potentials: multisensory stochastic resonance

    PubMed Central

    Huidobro, Nayeli; Silva, Mayte; Flores, Amira; Trenado, Carlos; Quintanar, Luis; Arias-Carrión, Oscar; Kristeva, Rumyana

    2015-01-01

    The present investigation documents the electrophysiological occurrence of multisensory stochastic resonance in the human visual pathway elicited by tactile noise. We define multisensory stochastic resonance of brain evoked potentials as the phenomenon in which an intermediate level of input noise of one sensory modality enhances the brain evoked response of another sensory modality. Here we examined this phenomenon in visual evoked potentials (VEPs) modulated by the addition of tactile noise. Specifically, we examined whether a particular level of mechanical Gaussian noise applied to the index finger can improve the amplitude of the VEP. We compared the amplitude of the positive P100 VEP component between zero noise (ZN), optimal noise (ON), and high mechanical noise (HN). The data disclosed an inverted U-like graph for all the subjects, thus demonstrating the occurrence of a multisensory stochastic resonance in the P100 VEP. PMID:26156387

  2. Effect of mechanical tactile noise on amplitude of visual evoked potentials: multisensory stochastic resonance.

    PubMed

    Méndez-Balbuena, Ignacio; Huidobro, Nayeli; Silva, Mayte; Flores, Amira; Trenado, Carlos; Quintanar, Luis; Arias-Carrión, Oscar; Kristeva, Rumyana; Manjarrez, Elias

    2015-10-01

    The present investigation documents the electrophysiological occurrence of multisensory stochastic resonance in the human visual pathway elicited by tactile noise. We define multisensory stochastic resonance of brain evoked potentials as the phenomenon in which an intermediate level of input noise of one sensory modality enhances the brain evoked response of another sensory modality. Here we examined this phenomenon in visual evoked potentials (VEPs) modulated by the addition of tactile noise. Specifically, we examined whether a particular level of mechanical Gaussian noise applied to the index finger can improve the amplitude of the VEP. We compared the amplitude of the positive P100 VEP component between zero noise (ZN), optimal noise (ON), and high mechanical noise (HN). The data disclosed an inverted U-like graph for all the subjects, thus demonstrating the occurrence of a multisensory stochastic resonance in the P100 VEP. PMID:26156387

  3. Enhancement of the amplitude of somatosensory evoked potentials following magnetic pulse stimulation of the human brain.

    PubMed

    Seyal, M; Browne, J K; Masuoka, L K; Gabor, A J

    1993-01-01

    In this study we have demonstrated an enhancement of cortically generated wave forms of the somatosensory evoked potential (SEP) following magnetic pulse stimulation of the human brain. Subcortically generated activity was unaltered. The enhancement of SEP amplitude was greatest when the median nerve was stimulated 30-70 msec following magnetic pulse stimulation over the contralateral parietal scalp. We posit that the enhancement of the SEP is the result of synchronization of pyramidal cells in the sensorimotor cortex resulting from the magnetic pulse.

  4. Short latency compound action potentials from mammalian gravity receptor organs

    NASA Technical Reports Server (NTRS)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  5. Potential sensitivities in frequency modulation and heterodyne amplitude modulation Kelvin probe force microscopes

    PubMed Central

    2013-01-01

    In this paper, the potential sensitivity in Kelvin probe force microscopy (KPFM) was investigated in frequency modulation (FM) and heterodyne amplitude modulation (AM) modes. We showed theoretically that the minimum detectable contact potential difference (CPD) in FM-KPFM is higher than in heterodyne AM-KPFM. We experimentally confirmed that the signal-to-noise ratio in FM-KPFM is lower than that in heterodyne AM-KPFM, which is due to the higher minimum detectable CPD dependence in FM-KPFM. We also compared the corrugations in the local contact potential difference on the surface of Ge (001), which shows atomic resolution in heterodyne AM-KPFM. In contrast, atomic resolution cannot be obtained in FM-KPFM under the same experimental conditions. The higher potential resolution in heterodyne AM-KPFM was attributed to the lower crosstalk and higher potential sensitivity between topographic and potential measurements. PMID:24350866

  6. Potential sensitivities in frequency modulation and heterodyne amplitude modulation Kelvin probe force microscopes.

    PubMed

    Ma, Zong-Min; Mu, Ji-Liang; Tang, Jun; Xue, Hui; Zhang, Huan; Xue, Chen-Yang; Liu, Jun; Li, Yan-Jun

    2013-01-01

    In this paper, the potential sensitivity in Kelvin probe force microscopy (KPFM) was investigated in frequency modulation (FM) and heterodyne amplitude modulation (AM) modes. We showed theoretically that the minimum detectable contact potential difference (CPD) in FM-KPFM is higher than in heterodyne AM-KPFM. We experimentally confirmed that the signal-to-noise ratio in FM-KPFM is lower than that in heterodyne AM-KPFM, which is due to the higher minimum detectable CPD dependence in FM-KPFM. We also compared the corrugations in the local contact potential difference on the surface of Ge (001), which shows atomic resolution in heterodyne AM-KPFM. In contrast, atomic resolution cannot be obtained in FM-KPFM under the same experimental conditions. The higher potential resolution in heterodyne AM-KPFM was attributed to the lower crosstalk and higher potential sensitivity between topographic and potential measurements.

  7. Cognitive impairment correlates to low auditory event-related potential amplitudes in type 1 diabetes.

    PubMed

    Cooray, Gerald K; Maurex, Liselotte; Brismar, Tom

    2008-08-01

    Type 1 diabetes may be associated with a mild decline in cognitive function and mostly in mental speed. In order to study the pathophysiology of this, we have investigated auditory event-related potentials (AERP) and their relation to cognitive function in diabetes patients. AERP was recorded in patients with type 1 diabetes (n=119) and in a healthy control group (n=61). AERP was obtained with an odd-ball and a two-stimulus paradigm. Cognitive function was evaluated in 10 domains in the patients. Patients had normal N100 latency, but a highly significant decrease in auditory N100 amplitude (p<10(-6)), which correlated with a decrease in psychomotor speed but not with function in other domains. Psychomotor speed also correlated with P300 amplitude, although P300 amplitude was only slightly decreased in the patients. Even stronger correlations were found with the parietal N100-P300 peak-to-peak amplitude, which correlated both to psychomotor speed (rho=0.61, p<10(-7)) and processing speed (p<0.005). P300 latency was increased in patients, and this correlated to low global cognitive score and older age. We conclude that the decline in psychomotor speed in type 1 diabetes is associated with a highly significant decrease in the auditory N100 peak amplitude. This association and the relatively small abnormality in P300 latency is quite different from those generally found in dementia, and suggest that the underlying defect is located in the brain stem or the white matter. Presumably small conduction defects in ascending fibers can distort the firing synchrony necessary for signal generation in the cortex. PMID:18650025

  8. Transforming echoes into pseudo-action potentials for classifying plants.

    PubMed

    Kuc, R

    2001-10-01

    Animals perceive their environment by converting sensory stimuli into action potentials, or temporal point processes, that are interpreted by the brain. This paper investigates the information content of point processes extracted from echoes from in situ plants in an effort to understand how bats recognize landmarks in the field. A mobile sonar converts echoes into biologically similar temporal point processes. termed pseudo-action potentials (PAPs), whose inter-PAP interval relates to echo amplitude. The sonar forms a sector scan of an object to produce a spatial-temporal PAP field. Classifier neurons apply delays and coincidence detection to the PAP field to identify three distinct echo types, glints, blobs, and fuzz, which characterize plant features. Glints are large amplitude echoes exhibiting coherence over successive echoes in the sector scan, typically produced by favorably oriented isolated specular reflectors. Blobs are large echoes lacking coherence, typically bordering glints or formed by collections of interfering reflectors. Fuzz represents weak echoes, typically produced by collection of weak scatterers or by reflectors on the beam periphery. A small mirror reflector models a flat leaf surface and motivates the glint criteria. Classifiers are applied to experimental data from two types of tree trunks, a glint-producing sycamore (Platanus occidenatalis) and a glint-absent Norway maple (Acer platanoides) and two plants, a glint-producing rhododendron (Rhododendron maximus) and a glint-absent yew (Taxus media). We speculate that our narrow-band sonar models the activity of a single frequency bin in the frequency-modulated (FM) sweep emitted by bats, and that one function of the frequency bins in the FM sweep is to form a sector scan of the environment.

  9. Dipole characterization of single neurons from their extracellular action potentials

    PubMed Central

    Victor, Jonathan D.

    2011-01-01

    The spatial variation of the extracellular action potentials (EAP) of a single neuron contains information about the size and location of the dominant current source of its action potential generator, which is typically in the vicinity of the soma. Using this dependence in reverse in a three-component realistic probe + brain + source model, we solved the inverse problem of characterizing the equivalent current source of an isolated neuron from the EAP data sampled by an extracellular probe at multiple independent recording locations. We used a dipole for the model source because there is extensive evidence it accurately captures the spatial roll-off of the EAP amplitude, and because, as we show, dipole localization, beyond a minimum cell-probe distance, is a more accurate alternative to approaches based on monopole source models. Dipole characterization is separable into a linear dipole moment optimization where the dipole location is fixed, and a second, nonlinear, global optimization of the source location. We solved the linear optimization on a discrete grid via the lead fields of the probe, which can be calculated for any realistic probe + brain model by the finite element method. The global source location was optimized by means of Tikhonov regularization that jointly minimizes model error and dipole size. The particular strategy chosen reflects the fact that the dipole model is used in the near field, in contrast to the typical prior applications of dipole models to EKG and EEG source analysis. We applied dipole localization to data collected with stepped tetrodes whose detailed geometry was measured via scanning electron microscopy. The optimal dipole could account for 96% of the power in the spatial variation of the EAP amplitude. Among various model error contributions to the residual, we address especially the error in probe geometry, and the extent to which it biases estimates of dipole parameters. This dipole characterization method can be applied to

  10. [A significant increase in intraoperative flash visual evoked potential amplitude during craniopharyngioma surgery-case report].

    PubMed

    Kawaguchi, Tomohiro; Ogawa, Yoshikazu; Fujiwara, Satoru; Tominaga, Teiji

    2015-04-01

    The flash visual evoked potential (VEP) is a useful diagnostic modality for visual preservation during surgery. Decreased VEP amplitude is recognized to indicate visual deterioration;however, whether intraoperative VEP can detect visual improvement remains unclear. We describe a craniopharyngioma case with a significant increase in VEP amplitude during surgery. A 67-year-old woman presented with progressive gait disturbance and impaired consciousness. Head magnetic resonance imaging demonstrated a sellar-suprasellar tumor compressing the optic chiasm upward with significant ventricular dilation. Her Glasgow Coma Scale was E3V3M5. Visual fields and acuity could not be examined because of impaired consciousness, and she could not see/recognize objects on a table. Preoperative VEP showed reproducible waveforms. Tumor removal by the extended transsphenoidal approach was performed with VEP monitoring. Increased VEP amplitude was observed after dural incision and persisted until the surgery ended. Postoperative VEP waveforms were also reproducible, but visual fields/acuity could not be examined because of cognitive dysfunction. Useful visual function was restored, and she became independent in daily life. The histological diagnosis was craniopharyngioma. The patient underwent ventriculo-peritoneal shunting for hydrocephalus 16 days after tumor removal. The postoperative course was uneventful and she was transferred to another hospital for rehabilitation. Intraoperative VEP may indicate visual improvement during surgery, which is a useful objective assessment for visual function in patients with impaired consciousness and cognitive dysfunction.

  11. Effects of complex tonal stimuli on latency and amplitude of a late auditory evoked potential.

    PubMed

    Marx, Charles G; Goshorn, Edward L

    2016-05-01

    An optimum stimulus for evoking late auditory potentials is not well established. A typical stimulus for clinical purposes is either a brief speech signal or a brief single-frequency tone. Based on previous research, it is reasonable to assume that a complex stimulus may enhance waveform morphology relative to a single-frequency stimulus. The current project investigated the effects on P1 latency and P1/N1 amplitude of a two-frequency complex stimulus with the second frequency having either a dissonant or harmonic relationship to a single-frequency reference stimulus. An 80 ms 1000 Hz tone with 10 ms rise/fall times served as the reference stimulus. The two-frequency complex stimuli consisted of the reference (1000 Hz) frequency mixed with a second frequency of equal duration and amplitude at 1100, 1250, 1500, 2000, or 4000 Hz, resulting in three dissonant and two harmonic stimuli. One dissonant stimulus (1000 + 1100 Hz) was designed to fall within the critical band of the reference stimulus. Stimuli were presented in a counterbalanced order to 20 normal hearing adult subjects. Two replicate runs were obtained for each stimulus condition. Results showed that the complex stimuli had no significant effect on P1 latency relative to the reference stimulus, but produced a significant increase in P1/N1 amplitude for the harmonic stimuli. PMID:27250127

  12. [A significant increase in intraoperative flash visual evoked potential amplitude during craniopharyngioma surgery-case report].

    PubMed

    Kawaguchi, Tomohiro; Ogawa, Yoshikazu; Fujiwara, Satoru; Tominaga, Teiji

    2015-04-01

    The flash visual evoked potential (VEP) is a useful diagnostic modality for visual preservation during surgery. Decreased VEP amplitude is recognized to indicate visual deterioration;however, whether intraoperative VEP can detect visual improvement remains unclear. We describe a craniopharyngioma case with a significant increase in VEP amplitude during surgery. A 67-year-old woman presented with progressive gait disturbance and impaired consciousness. Head magnetic resonance imaging demonstrated a sellar-suprasellar tumor compressing the optic chiasm upward with significant ventricular dilation. Her Glasgow Coma Scale was E3V3M5. Visual fields and acuity could not be examined because of impaired consciousness, and she could not see/recognize objects on a table. Preoperative VEP showed reproducible waveforms. Tumor removal by the extended transsphenoidal approach was performed with VEP monitoring. Increased VEP amplitude was observed after dural incision and persisted until the surgery ended. Postoperative VEP waveforms were also reproducible, but visual fields/acuity could not be examined because of cognitive dysfunction. Useful visual function was restored, and she became independent in daily life. The histological diagnosis was craniopharyngioma. The patient underwent ventriculo-peritoneal shunting for hydrocephalus 16 days after tumor removal. The postoperative course was uneventful and she was transferred to another hospital for rehabilitation. Intraoperative VEP may indicate visual improvement during surgery, which is a useful objective assessment for visual function in patients with impaired consciousness and cognitive dysfunction. PMID:25838303

  13. A simple derivation for amplitude and time period of charged particles in an electrostatic bathtub potential

    NASA Astrophysics Data System (ADS)

    Prathap Reddy, K.

    2016-11-01

    An ‘electrostatic bathtub potential’ is defined and analytical expressions for the time period and amplitude of charged particles in this potential are obtained and compared with simulations. These kinds of potentials are encountered in linear electrostatic ion traps, where the potential along the axis appears like a bathtub. Ion traps are used in basic physics research and mass spectrometry to store ions; these stored ions make oscillatory motion within the confined volume of the trap. Usually these traps are designed and studied using ion optical software, but in this work the bathtub potential is reproduced by making two simple modifications to the harmonic oscillator potential. The addition of a linear ‘k 1|x|’ potential makes the simple harmonic potential curve steeper with a sharper turn at the origin, while the introduction of a finite-length zero potential region at the centre reproduces the flat region of the bathtub curve. This whole exercise of modelling a practical experimental situation in terms of a well-known simple physics problem may generate interest among readers.

  14. Understanding the electrical behavior of the action potential in terms of elementary electrical sources.

    PubMed

    Rodriguez-Falces, Javier

    2015-03-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity.

  15. Action potential broadening in a presynaptic channelopathy

    NASA Astrophysics Data System (ADS)

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-07-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

  16. Action potential broadening in a presynaptic channelopathy

    PubMed Central

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-01-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID:27381274

  17. Action potential broadening in a presynaptic channelopathy.

    PubMed

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E; Kullmann, Dimitri M

    2016-01-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca(2+) influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID:27381274

  18. Ontogeny of vestibular compound action potentials in the domestic chicken

    NASA Technical Reports Server (NTRS)

    Jones, S. M.; Jones, T. A.

    2000-01-01

    Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

  19. Effect of postextrasystolic potentiation on amplitude and timing of regional left ventricular wall motion in ischaemic heart disease.

    PubMed Central

    Gibson, D G; Fleck, E; Rudolph, W

    1983-01-01

    In order to investigate the effects of postextrasystolic potentiation on left ventricular wall motion, the left ventriculograms of 30 patients were digitised frame by frame and regional movement demonstrated by contour displays. Postextrasystolic potentiation caused significant increases in end-diastolic volume, ejection fraction, and peak ejection and filling rates. The amplitude of normally moving segments increased by 5.7 +/- 2.3 mm, regardless of initial amplitude. Hypokinetic segments moved normally if the initial amplitude was greater than 5 mm, and there was a reduced or absent response if 4 mm or less. Four specific abnormalities of timing of motion were studied during isovolumic contraction, early ejection, and isovolumic relaxation. Their timing and extent were all unaffected in postextrasystolic beats. These results thus give no evidence for the entity "reversible asynergy". Rather, they suggest that the response of local wall motion to postextrasystolic potentiation depends only on basal amplitude and increased volume change in postextrasystolic beats. PMID:6188474

  20. Responsivity to dyslexia training indexed by the N170 amplitude of the brain potential elicited by word reading.

    PubMed

    Fraga González, G; Žarić, G; Tijms, J; Bonte, M; Blomert, L; Leppänen, P; van der Molen, M W

    2016-07-01

    The present study examined training effects in dyslexic children on reading fluency and the amplitude of N170, a negative brain-potential component elicited by letter and symbol strings. A group of 18 children with dyslexia in 3rd grade (9.05±0.46years old) was tested before and after following a letter-speech sound mapping training. A group of 20 third-grade typical readers (8.78±0.35years old) performed a single time on the same brain potential task. The training was differentially effective in speeding up reading fluency in the dyslexic children. In some children, training had a beneficial effect on reading fluency ('improvers') while a training effect was absent in others ('non-improvers'). Improvers at pre-training showed larger N170 amplitude to words compared to non-improvers. N170 amplitude decreased following training in improvers but not in non-improvers. But the N170 amplitude pattern in improvers continued to differ from the N170 amplitude pattern across hemispheres seen in typical readers. Finally, we observed a positive relation between the decrease in N170 amplitude and gains in reading fluency. Collectively, the results that emerged from the present study indicate the sensitivity of N170 amplitude to reading fluency and its potential as a predictor of reading fluency acquisition. PMID:27200495

  1. Responsivity to dyslexia training indexed by the N170 amplitude of the brain potential elicited by word reading.

    PubMed

    Fraga González, G; Žarić, G; Tijms, J; Bonte, M; Blomert, L; Leppänen, P; van der Molen, M W

    2016-07-01

    The present study examined training effects in dyslexic children on reading fluency and the amplitude of N170, a negative brain-potential component elicited by letter and symbol strings. A group of 18 children with dyslexia in 3rd grade (9.05±0.46years old) was tested before and after following a letter-speech sound mapping training. A group of 20 third-grade typical readers (8.78±0.35years old) performed a single time on the same brain potential task. The training was differentially effective in speeding up reading fluency in the dyslexic children. In some children, training had a beneficial effect on reading fluency ('improvers') while a training effect was absent in others ('non-improvers'). Improvers at pre-training showed larger N170 amplitude to words compared to non-improvers. N170 amplitude decreased following training in improvers but not in non-improvers. But the N170 amplitude pattern in improvers continued to differ from the N170 amplitude pattern across hemispheres seen in typical readers. Finally, we observed a positive relation between the decrease in N170 amplitude and gains in reading fluency. Collectively, the results that emerged from the present study indicate the sensitivity of N170 amplitude to reading fluency and its potential as a predictor of reading fluency acquisition.

  2. Chronic network stimulation enhances evoked action potentials

    NASA Astrophysics Data System (ADS)

    Ide, A. N.; Andruska, A.; Boehler, M.; Wheeler, B. C.; Brewer, G. J.

    2010-02-01

    Neurons cultured on multielectrode arrays almost always lack external stimulation except during the acute experimental phase. We have investigated the effects of chronic stimulation during the course of development in cultured hippocampal neural networks by applying paired pulses at half of the electrodes for 0, 1 or 3 r/day for 8 days. Spike latencies increased from 4 to 16 ms as the distance from the stimulus increased from 200 to 1700 µm, suggesting an average of four synapses over this distance. Compared to no chronic stimulation, our results indicate that chronic stimulation increased evoked spike counts per stimulus by 50% at recording sites near the stimulating electrode and increased the instantaneous firing rate. On trials where both pulses elicited responses, spike count was 40-80% higher than when only one of the pulses elicited a response. In attempts to identify spike amplitude plasticity, we found mainly amplitude variation with different latencies suggesting recordings from neurons with different identities. These data suggest plastic network changes induced by chronic stimulation that enhance the reliability of information transmission and the efficiency of multisynaptic network communication.

  3. Action potential initiation and propagation in rat neocortical pyramidal neurons.

    PubMed

    Stuart, G; Schiller, J; Sakmann, B

    1997-12-15

    1. Initiation and propagation of action potentials evoked by extracellular synaptic stimulation was studied using simultaneous dual and triple patch pipette recordings from different locations on neocortical layer 5 pyramidal neurons in brain slices from 4-week-old rats (P26-30) at physiological temperatures. 2. Simultaneous cell-attached and whole-cell voltage recordings from the apical trunk (up to 700 microns distal to the soma) and the soma indicated that proximal synaptic stimulation (layer 4) initiated action potentials first at the soma, whereas distal stimulation (upper layer 2/3) could initiate dendritic regenerative potentials prior to somatic action potentials following stimulation at higher intensity. 3. Somatic action potentials, once initiated, propagated back into the apical dendrites in a decremented manner which was frequency dependent. The half-width of back propagating action potentials increased and their maximum rate of rise decreased with distance from the soma, with the peak of these action potentials propagating with a conduction velocity of approximately 0.5 m s-1. 4. Back-propagation of action potentials into the dendritic tree was associated with dendritic calcium electrogenesis, which was particularly prominent during bursts of somatic action potentials. 5. When dendritic regenerative potentials were evoked prior to somatic action potentials, the more distal the dendritic recording was made from the soma the longer the time between the onset of the dendritic regenerative potential relative to somatic action potential. This suggested that dendritic regenerative potentials were initiated in the distal apical dendrites, possibly in the apical tuft. 6. At any one stimulus intensity, the initiation of dendritic regenerative potentials prior to somatic action potentials could fluctuate, and was modulated by depolarizing somatic or hyperpolarizing dendritic current injection. 7. Dendritic regenerative potentials could be initiated prior to

  4. Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

    PubMed

    Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

    2012-01-01

    Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. PMID:21728204

  5. Naturalistic stimulation changes the dynamic response of action potential encoding in a mechanoreceptor

    PubMed Central

    Pfeiffer, Keram; French, Andrew S.

    2015-01-01

    Naturalistic signals were created from vibrations made by locusts walking on a Sansevieria plant. Both naturalistic and Gaussian noise signals were used to mechanically stimulate VS-3 slit-sense mechanoreceptor neurons of the spider, Cupiennius salei, with stimulus amplitudes adjusted to give similar firing rates for either stimulus. Intracellular microelectrodes recorded action potentials, receptor potential, and receptor current, using current clamp and voltage clamp. Frequency response analysis showed that naturalistic stimulation contained relatively more power at low frequencies, and caused increased neuronal sensitivity to higher frequencies. In contrast, varying the amplitude of Gaussian stimulation did not change neuronal dynamics. Naturalistic stimulation contained less entropy than Gaussian, but signal entropy was higher than stimulus in the resultant receptor current, indicating addition of uncorrelated noise during transduction. The presence of added noise was supported by measuring linear information capacity in the receptor current. Total entropy and information capacity in action potentials produced by either stimulus were much lower than in earlier stages, and limited to the maximum entropy of binary signals. We conclude that the dynamics of action potential encoding in VS-3 neurons are sensitive to the form of stimulation, but entropy and information capacity of action potentials are limited by firing rate. PMID:26578975

  6. Conduction velocity of antigravity muscle action potentials.

    PubMed

    Christova, L; Kosarov, D; Christova, P

    1992-01-01

    The conduction velocity of the impulses along the muscle fibers is one of the parameters of the extraterritorial potentials of the motor units allowing for the evaluation of the functional state of the muscles. There are no data about the conduction velocities of antigravity muscleaction potentials. In this paper we offer a method for measuring conduction velocity of potentials of single MUs and the averaged potentials of the interference electromiogram (IEMG) lead-off by surface electrodes from mm. sternocleidomastoideus, trapezius, deltoideus (caput laterale) and vastus medialis. The measured mean values of the conduction velocity of antigravity muscles potentials can be used for testing the functional state of the muscles.

  7. Variety of the Wave Change in Compound Muscle Action Potential in an Animal Model

    PubMed Central

    Ito, Zenya; Ando, Kei; Muramoto, Akio; Kobayashi, Kazuyoshi; Hida, Tetsuro; Ito, Kenyu; Ishikawa, Yoshimoto; Tsushima, Mikito; Matsumoto, Akiyuki; Tanaka, Satoshi; Morozumi, Masayoshi; Matsuyama, Yukihiro; Ishiguro, Naoki

    2015-01-01

    Study Design Animal study. Purpose To review the present warning point criteria of the compound muscle action potential (CMAP) and investigate new criteria for spinal surgery safety using an animal model. Overview of Literature Little is known about correlation palesis and amplitude of spinal cord monitoring. Methods After laminectomy of the tenth thoracic spinal lamina, 2-140 g force was delivered to the spinal cord with a tension gage to create a bilateral contusion injury. The study morphology change of the CMAP wave and locomotor scale were evaluated for one month. Results Four different types of wave morphology changes were observed: no change, amplitude decrease only, morphology change only, and amplitude and morphology change. Amplitude and morphology changed simultaneously and significantly as the injury force increased (p<0.05) Locomotor scale in the amplitude and morphology group worsened more than the other groups. Conclusions Amplitude and morphology change of the CMAP wave exists and could be the key of the alarm point in CMAP. PMID:26713129

  8. Ratio between the amplitude of sensory evoked potentials at the wrist in both hands of left-handed subjects.

    PubMed Central

    Martínez, A C; Conde, M C; Campo, F D; Mingo, P; Ferrer, M T

    1980-01-01

    Maximum sensory conduction velocity, duration and amplitude of the sensory evoked potentials at the wrist on stimulating digits 1, 2, 3 and 5, were determined bilaterally in 21 left-handed subjects with an age range from 6 to 47 years. The amplitude of the sensory evoked potential at the wrist was larger in the right hand. This asymmetry is the reverse of the one previously observed in right-handed infants and adults. It could be physiological and suggests a difference in density of sensory innervation between the two hands. Asymmetry of sensory innervation can be helpful in the study of hand dominance. PMID:7359155

  9. Determining the True Polarity and Amplitude of Synaptic Currents Underlying Gamma Oscillations of Local Field Potentials

    PubMed Central

    Makarov, Valeri A.; Herreras, Oscar

    2013-01-01

    Fluctuations in successive waves of oscillatory local field potentials (LFPs) reflect the ongoing processing of neuron populations. However, their amplitude, polarity and synaptic origin are uncertain due to the blending of electric fields produced by multiple converging inputs, and the lack of a baseline in standard AC-coupled recordings. Consequently, the estimation of underlying currents by laminar analysis yields spurious sequences of inward and outward currents. We devised a combined analytical/experimental approach that is suitable to study laminated structures. The approach was essayed on an experimental oscillatory LFP as the Schaffer-CA1 gamma input in anesthetized rats, and it was verified by parallel processing of model LFPs obtained through a realistic CA1 aggregate of compartmental units. This approach requires laminar LFP recordings and the isolation of the oscillatory input from other converging pathways, which was achieved through an independent component analysis. It also allows the spatial and temporal components of pathway-specific LFPs to be separated. While reconstructed Schaffer-specific LFPs still show spurious inward/outward current sequences, these were clearly stratified into distinct subcellular domains. These spatial bands guided the localized delivery of neurotransmitter blockers in experiments. As expected, only Glutamate but not GABA blockers abolished Schaffer LFPs when applied to the active but not passive subcellular domains of pyramidal cells. The known chemical nature of the oscillatory LFP allowed an empirical offset of the temporal component of Schaffer LFPs, such that following reconstruction they yield only sinks or sources at the appropriate sites. In terms of number and polarity, some waves increased and others decreased proportional to the concomitant inputs in native multisynaptic LFPs. Interestingly, the processing also retrieved the initiation time for each wave, which can be used to discriminate afferent from

  10. Selective effects of an octopus toxin on action potentials

    PubMed Central

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

    1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

  11. Transient outward currents and action potential alterations in rabbit ventricular myocytes.

    PubMed

    Kawano, S; Hiraoka, M

    1991-06-01

    To clarify ionic mechanisms underlying successive changes in action potential repolarization upon sudden increase in driving rate or initiation of rapid drive after a rest, membrane potentials and currents were recorded from isolated rabbit ventricular myocytes using the suction-pipette whole-cell clamp method. When 20 action potentials were elicited with a stimulus frequency of 2.0 Hz after a rest period of 20 s, the plateau and action potential duration showed complex changes in successive beats, whereas they were nearly constant with stimulation at 0.1 Hz. There were only weak correlations between changes in action potential parameters and preceding diastolic intervals. The changes were prominent in the first 10 beats but subsided gradually thereafter, attaining nearly steady configurations of action potentials. When depolarizing pulses were applied at a fast rate, under the voltage clamp, the amplitudes of the initial inward current in the presence of tetrodotoxin changed greatly depending on the pulse numbers and diastolic intervals, whereas the delayed outward K+ current changed little. Variations of the initial inward current in successive pulses were caused by different degrees of activation and recovery from inactivation in the Ca2+ current, the Ca(2+)-sensitive and -insensitive transient outward current. While inhibition of either one or two current components decreased the action potential alterations, blocking the three components completely abolished them. These results indicate that alterations of the Ca(2+)-sensitive and -insensitive transient outward current together with the Ca2+ current contribute to the action potential alterations after initiation of rapid drive or an increase in driving rates.

  12. Effect of nanomaterials on the compound action potential of the shore crab, Carcinus maenas.

    PubMed

    Windeatt, Kirsten M; Handy, Richard D

    2013-06-01

    Little is known about the effects of manufactured nanomaterials on the function of nerves. The experiment aimed to test the effects of three different nanomaterials (1 mg l⁻¹ of TiO₂ NPs, Ag NPs or SWCNT) on the compound action potential of the shore crab (Carcinus maenas) compared with an appropriate bulk powder or metal salt control (bulk TiO₂ powder, AgNO₃ and carbon black respectively). In single action potential recordings, there were no effects of any of the nanomaterials on the peak amplitude, duration, rate of rise (depolarisation), or rate of decrease (repolarisation) of the compound action potential in crab saline, despite settling of each nanomaterial directly onto the nerve preparation. The ability of the crab nerve to be stimulated to tetanus was also unaffected by exposure to the nanomaterials compared with the appropriate bulk powder or metal salt control. Solvent controls with sodium dodecyl sulfate (SDS) also had no effect on action potentials. Overall, the study concludes that there were no effects of the materials at the concentrations tested on the compound action potential of the shore crab in physiological saline. PMID:22394242

  13. ATP-sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction.

    PubMed

    Nichols, C G; Ripoll, C; Lederer, W J

    1991-01-01

    The role of ATP-sensitive potassium (KATP) channels in modulating the action potential and contraction of guinea pig ventricular myocytes was investigated. Under voltage clamp, the maximum whole-cell KATP channel conductance was estimated (195 +/- 10 nS, n = 6) by exposing the cells to complete metabolic blockade (2 mM cyanide in the presence of 10 mM 2-deoxy-glucose). In isolated inside-out membrane patches, the ATP dependence of KATP channel activity under relevant conditions was measured (half-maximal inhibition at 114 microM). Under current clamp (with intracellular ATP concentration = 5 mM), the effect of graded KATP channel activation on the action potential and the twitch was estimated by injection of a current (proportional to voltage) that simulated the KATP conductance. As this "conductance" was increased, the action potential was shortened, and contractile amplitude declined, as expected. From the results of these experiments, the quantitative dependence of the action potential duration on intracellular ATP concentration was estimated, without relying on a mathematical model of the cell membrane. The results imply that KATP-dependent action potential shortening is likely to occur if ATP concentration falls below normal levels (approximately 5 mM), as may happen regionally, or globally, during myocardial ischemia.

  14. Increased Event-Related Potentials and Alpha-, Beta-, and Gamma-Activity Associated with Intentional Actions

    PubMed Central

    Karch, Susanne; Loy, Fabian; Krause, Daniela; Schwarz, Sandra; Kiesewetter, Jan; Segmiller, Felix; Chrobok, Agnieszka I.; Keeser, Daniel; Pogarell, Oliver

    2016-01-01

    Objective: Internally guided actions are defined as being purposeful, self-generated and offering choices between alternatives. Intentional actions are essential to reach individual goals. In previous empirical studies, internally guided actions were predominantly related to functional responses in frontal and parietal areas. The aim of the present study was to distinguish event-related potentials and oscillatory responses of intentional actions and externally guided actions. In addition, we compared neurobiological findings of the decision which action to perform with those referring to the decision whether or not to perform an action. Methods: Twenty-eight subjects participated in adapted go/nogo paradigms, including a voluntary selection condition allowing participants to (1) freely decide whether to press the response button or (2) to decide whether they wanted to press the response button with the right index finger or the left index finger. Results: The reaction times were increased when participants freely decided whether and how they wanted to respond compared to the go condition. Intentional processes were associated with a fronto-centrally located N2 and P3 potential. N2 and P3 amplitudes were increased during intentional actions compared to instructed responses (go). In addition, increased activity in the alpha-, beta- and gamma-frequency range was shown during voluntary behavior rather than during externally guided responses. Conclusion: These results may indicate that an additional cognitive process is needed for intentional actions compared to instructed behavior. However, the neural responses were comparatively independent of the kind of decision that was made (1) decision which action to perform; (2) decision whether or not to perform an action). Significance: The study demonstrates the importance of fronto-central alpha-, beta-, and gamma oscillations for voluntary behavior. PMID:26834680

  15. Toward a system to measure action potential on mice brain slices with local magnetoresistive probes

    SciTech Connect

    Amaral, J.; Cardoso, S.; Freitas, P. P.; Sebastiao, A. M.

    2011-04-01

    This work combines an electrophysiological system with a magnetoresistive chip to measure the magnetic field created by the synaptic/action potential currents. The chip, with 15 spin valve sensors, was designed to be integrated in a recording chamber for submerged mice brain slices used for synaptic potential measurements. Under stimulation (rectangular pulses of 0.1 ms every 10 s) through a concentric electrode placed near the CA3/CA1 border of the hippocampus, the spin valve sensor readout signals with 20 {mu}V amplitude and a pulse length of 20 to 30 ms were recorded only in the pyramidal cell bodies region and can be interpreted as being derived from action potentials/currents.

  16. Toward a system to measure action potential on mice brain slices with local magnetoresistive probes

    NASA Astrophysics Data System (ADS)

    Amaral, J.; Cardoso, S.; Freitas, P. P.; Sebastião, A. M.

    2011-04-01

    This work combines an electrophysiological system with a magnetoresistive chip to measure the magnetic field created by the synaptic/action potential currents. The chip, with 15 spin valve sensors, was designed to be integrated in a recording chamber for submerged mice brain slices used for synaptic potential measurements. Under stimulation (rectangular pulses of 0.1 ms every 10 s) through a concentric electrode placed near the CA3/CA1 border of the hippocampus, the spin valve sensor readout signals with 20 μV amplitude and a pulse length of 20 to 30 ms were recorded only in the pyramidal cell bodies region and can be interpreted as being derived from action potentials/currents.

  17. Compound action potentials recorded in the human spinal cord during neurostimulation for pain relief.

    PubMed

    Parker, John L; Karantonis, Dean M; Single, Peter S; Obradovic, Milan; Cousins, Michael J

    2012-03-01

    Electrical stimulation of the spinal cord provides effective pain relief to hundreds of thousands of chronic neuropathic pain sufferers. The therapy involves implantation of an electrode array into the epidural space of the subject and then stimulation of the dorsal column with electrical pulses. The stimulation depolarises axons and generates propagating action potentials that interfere with the perception of pain. Despite the long-term clinical experience with spinal cord stimulation, the mechanism of action is not understood, and no direct evidence of the properties of neurons being stimulated has been presented. Here we report novel measurements of evoked compound action potentials from the spinal cords of patients undergoing stimulation for pain relief. The results reveal that Aβ sensory nerve fibres are recruited at therapeutic stimulation levels and the Aβ potential amplitude correlates with the degree of coverage of the painful area. Aβ-evoked responses are not measurable below a threshold stimulation level, and their amplitude increases with increasing stimulation current. At high currents, additional late responses are observed. Our results contribute towards efforts to define the mechanism of spinal cord stimulation. The minimally invasive recording technique we have developed provides data previously obtained only through microelectrode techniques in spinal cords of animals. Our observations also allow the development of systems that use neuronal recording in a feedback loop to control neurostimulation on a continuous basis and deliver more effective pain relief. This is one of numerous benefits that in vivo electrophysiological recording can bring to a broad range of neuromodulation therapies. PMID:22188868

  18. Intensity-amplitude relationships in monkey event-related potentials: parallels to human augmenting-reducing responses.

    PubMed

    Pineda, J A; Holmes, T C; Foote, S L

    1991-06-01

    In human, the amplitudes of specific event-related potential (ERP) components can increase or decrease in response to increasing stimulus intensity depending on the location of the recording site. Large increases characterize components presumably generated by modality-specific sites, while smaller increases or even decreases are associated with those originating in associational areas. Comparable data from non-human primates, which would permit invasive studies of the neural substrates underlying these intensity-amplitude differences, are limited. To more fully characterize these relationships, auditory ERPs were recorded from chronically implanted epidural electrodes in 5 squirrel monkeys (Saimiri sciureus) in response to tones (500 Hz, 300 msec duration) of varying intensities (50, 60, 70, 80 dB SPL). Squirrel monkey ERPs recorded at Fz exhibited 3 peaks during the 200 msec post-stimulus interval. These peaks included a positivity (P1), followed by a negativity (N1), and then another positivity (P2). At posterior sites, the frontal P1-N1 configuration was recorded as an N1-P1 complex. At these sites, a small negativity (N2) preceded the last positive peak (P2). Changes in polarity were independent of reference site and posterior N1-P1 peaks exhibited latencies similar to those of the frontal P1-N1 components. Amplitudes at Fz, Cz, and Pz increased substantially with increasing stimulus intensity ('augmenting'). In contrast, only small increases or even decreases in amplitude ('reducing') were evident at T3 and T4. On the other hand, peak latencies decreased with higher stimulus intensities at most sites. The site-specific amplitude responses exhibited considerable temporal stability. In one subject, for example, similar 'augmenting' profiles were recorded at Fz in 8 sessions over a 6-month period. The topography of monkey intensity-amplitude response profiles, their temporal stability, and peak latency shifts resemble observations made in humans. The data show

  19. [On the theory of action potential propagation in plant cells].

    PubMed

    Sizonenko, V L; Kovalenko, N I

    2012-01-01

    The distribution of an electric field in plant cells and zooblasts has been investigated at propagation of the action potential. The behavior of ions in the cytoplasm and in the extracellular fluid has been described with the equations of electric charge motion in the electrolytes. It has been shown that the action potential causes an electric potential change not only in the depth of the cytoplasm but also in the extracellular area far from the lipidic bilayer. The biomembrane resistance has been expressed by physical parameters of a cell, such as ionic diffusion coefficient in fluid, Debye-Huckel radius, dielectric conductivity etc. The presence of breakings in the action potential diagrams has been explained as a result of insufficient resolving power of the measuring devices at the instant the sodium ionic canals of the bilayer opens. PMID:23035528

  20. Direction of action potential propagation influences calcium increases in distal dendrites of the cricket giant interneurons.

    PubMed

    Ogawa, Hiroto; Baba, Yoshichika; Oka, Kotaro

    2002-10-01

    To understand the relationship between the propagation direction of action potentials and dendritic Ca(2+) elevation, simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and intradendritic membrane potential were performed in the wind-sensitive giant interneurons of the cricket. The dendritic Ca(2+) transients induced by synaptically-evoked action potentials had larger amplitudes than those induced by backpropagating spikes evoked by antidromic stimulation. The amplitude of the [Ca(2+)](i) changes induced by antidromic stimuli combined with subthreshold synaptic stimulation was not different from that of the Ca(2+) increases evoked by the backpropagating spikes alone. This result means that the synaptically activated Ca(2+) release from intracellular stores does not contribute to enhancement of Ca(2+) elevation induced by backpropagating spikes. On the other hand, the synaptically evoked action potentials were also increased at distal dendrites in which the Ca(2+) elevation was enhanced. When the dendritic and axonal spikes were simultaneously recorded, the delay between dendritic spike and ascending axonal spike depended upon which side of the cercal nerves was stimulated. Further, dual intracellular recording at different dendritic branches illustrated that the dendritic spike at the branch arborizing on the stimulated side preceded the spike recorded at the other side of the dendrite. These results suggest that the spike-initiation site shifts depending on the location of the activated postsynaptic site. It is proposed that the difference of spike propagation manner could change the action potential waveform at the distal dendrite, and could produce synaptic activity-dependent Ca(2+) dynamics in the giant interneurons.

  1. The metabolic energy cost of action potential velocity

    NASA Astrophysics Data System (ADS)

    Crotty, Patrick; Sangrey, Thomas; Levy, William

    2006-03-01

    Voltage changes in neurons and other active cells are caused by the passage of ions across the cell membrane. These ionic currents depend on the transmembrane ion concentration gradients, which in unmyelinated axons are maintained during rest and restored after electrical activity by an ATPase sodium-potassium exchanger in the membrane. The amount of ATP consumed by this exchanger can be taken as the metabolic energy cost of any electrical activity in the axon. We use this measure, along with biophysical models of voltage-gated sodium and potassium ion channels, to quantify the energy cost of action potentials propagating in squid giant axons. We find that the energy of an action potential can be naturally divided into three separate components associated with different aspects of the action potential. We calculate these energy components as functions of the ion channel densities and axon diameters and find that the component associated with the rising phase and velocity of the action potential achieves a minimum near the biological values of these parameters. This result, which is robust with respect to other parameters such as temperature, suggests that evolution has optimized the axon for the energy of the action potential wavefront.

  2. Properties of Ca2+ sparks evoked by action potentials in mouse ventricular myocytes.

    PubMed

    Bridge, J H; Ershler, P R; Cannell, M B

    1999-07-15

    1. Calcium sparks were examined in enzymatically dissociated mouse cardiac ventricular cells using the calcium indicator fluo-3 and confocal microscopy. The properties of the mouse cardiac calcium spark are generally similar to those reported for other species. 2. Examination of the temporal relationship between the action potential and the time course of calcium spark production showed that calcium sparks are more likely to occur during the initial repolarization phase of the action potential. The latency of their occurrence varied by less than 1.4 ms (s.d.) and this low variability may be explained by the interaction of the gating of L-type calcium channels with the changes in driving force for calcium entry during the action potential. 3. When fixed sites within the cell are examined, calcium sparks have relatively constant amplitude but the amplitude of the sparks was variable among sites. The low variability of the amplitude of the calcium sparks suggests that more than one sarcoplasmic reticulum (SR) release channel must be involved in their genesis. Noise analysis (with the assumption of independent gating) suggests that > 18 SR calcium release channels may be involved in the generation of the calcium spark. At a fixed site, the response is close to 'all-or-none' behaviour which suggests that calcium sparks are indeed elementary events underlying cardiac excitation-contraction coupling. 4. A method for selecting spark sites for signal averaging is presented which allows the time course of the spark to be examined with high temporal and spatial resolution. Using this method we show the development of the calcium spark at high signal-to-noise levels.

  3. Contribution of auditory nerve fibers to compound action potential of the auditory nerve.

    PubMed

    Bourien, Jérôme; Tang, Yong; Batrel, Charlène; Huet, Antoine; Lenoir, Marc; Ladrech, Sabine; Desmadryl, Gilles; Nouvian, Régis; Puel, Jean-Luc; Wang, Jing

    2014-09-01

    Sound-evoked compound action potential (CAP), which captures the synchronous activation of the auditory nerve fibers (ANFs), is commonly used to probe deafness in experimental and clinical settings. All ANFs are believed to contribute to CAP threshold and amplitude: low sound pressure levels activate the high-spontaneous rate (SR) fibers, and increasing levels gradually recruit medium- and then low-SR fibers. In this study, we quantitatively analyze the contribution of the ANFs to CAP 6 days after 30-min infusion of ouabain into the round window niche. Anatomic examination showed a progressive ablation of ANFs following increasing concentration of ouabain. CAP amplitude and threshold plotted against loss of ANFs revealed three ANF pools: 1) a highly ouabain-sensitive pool, which does not participate in either CAP threshold or amplitude, 2) a less sensitive pool, which only encoded CAP amplitude, and 3) a ouabain-resistant pool, required for CAP threshold and amplitude. Remarkably, distribution of the three pools was similar to the SR-based ANF distribution (low-, medium-, and high-SR fibers), suggesting that the low-SR fiber loss leaves the CAP unaffected. Single-unit recordings from the auditory nerve confirmed this hypothesis and further showed that it is due to the delayed and broad first spike latency distribution of low-SR fibers. In addition to unraveling the neural mechanisms that encode CAP, our computational simulation of an assembly of guinea pig ANFs generalizes and extends our experimental findings to different species of mammals. Altogether, our data demonstrate that substantial ANF loss can coexist with normal hearing threshold and even unchanged CAP amplitude. PMID:24848461

  4. Differential action potentials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury.

    PubMed

    Zhang, Xu-Feng; Zhu, Chang Z; Thimmapaya, Rama; Choi, Won S; Honore, Prisca; Scott, Victoria E; Kroeger, Paul E; Sullivan, James P; Faltynek, Connie R; Gopalakrishnan, Murali; Shieh, Char-Chang

    2004-05-29

    The profile of tetrodotoxin sensitive (TTX-S) and resistant (TTX-R) Na(+) channels and their contribution to action potentials and firing patterns were studied in isolated small dorsal root ganglion (DRG) neurons after L5/L6 spinal nerve ligation (SNL). Total TTX-R Na(+) currents and Na(v) 1.8 mRNA were reduced in injured L5 DRG neurons 14 days after SNL. In contrast, TTX-R Na(+)currents and Na(v) 1.8 mRNA were upregulated in uninjured L4 DRG neurons after SNL. Voltage-dependent inactivation of TTX-R Na(+) channels in these neurons was shifted to hyperpolarized potentials by 4 mV. Two types of neurons were identified in injured L5 DRG neurons after SNL. Type I neurons (57%) had significantly lower threshold but exhibited normal resting membrane potential (RMP) and action potential amplitude. Type II neurons (43%) had significantly smaller action potential amplitude but retained similar RMP and threshold to those from sham rats. None of the injured neurons could generate repetitive firing. In the presence of TTX, only 26% of injured neurons could generate action potentials that had smaller amplitude, higher threshold, and higher rheobase compared with sham rats. In contrast, action potentials and firing patterns in uninjured L4 DRG neurons after SNL, in the presence or absence of TTX, were not affected. These results suggest that TTX-R Na(+) channels play important roles in regulating action potentials and firing patterns in small DRG neurons and that downregulation in injured neurons and upregulation in uninjured neurons confer differential roles in shaping electrogenesis, and perhaps pain transmission, in these neurons. PMID:15120592

  5. Expectation to feel more pain disrupts the habituation of laser-pain rating and laser-evoked potential amplitudes.

    PubMed

    Pazzaglia, Costanza; Testani, Elisa; Giordano, Rocco; Padua, Luca; Valeriani, Massimiliano

    2016-10-01

    Increased pain perception due to the expectation to feel more pain is called nocebo effect. The present study aimed at investigating whether: (1) the mere expectation to feel more pain after the administration of an inert drug can affect the laser-pain rating and the laser-evoked potential (LEP) amplitude, and (2) the learning potentiates the nocebo effect. Eighteen healthy volunteers were told that an inert cream, applied on the right hand, would increase the laser pain and LEP amplitude to right hand stimulation. They were randomly assigned to either "verbal session" or "conditioning session". In the "verbal session", LEPs to both right and left hand stimulation were recorded at the same intensity before (baseline) and after cream application. In the "conditioning session", after an initial cream application the laser stimulus intensity was increased surreptitiously to make the subjects believe that the treatment really increased the pain sensation. Then, the cream was reapplied, and LEPs were recorded at the same stimulus intensity as at the baseline. It was found that the verbal suggestion to feel more pain disrupted the physiological habituation of the laser-pain rating and LEP amplitude to treated (right) hand stimulation. Unlike previously demonstrated for the placebo effect, the learning did not potentiate the nocebo effect. PMID:27461877

  6. Expectation to feel more pain disrupts the habituation of laser-pain rating and laser-evoked potential amplitudes.

    PubMed

    Pazzaglia, Costanza; Testani, Elisa; Giordano, Rocco; Padua, Luca; Valeriani, Massimiliano

    2016-10-01

    Increased pain perception due to the expectation to feel more pain is called nocebo effect. The present study aimed at investigating whether: (1) the mere expectation to feel more pain after the administration of an inert drug can affect the laser-pain rating and the laser-evoked potential (LEP) amplitude, and (2) the learning potentiates the nocebo effect. Eighteen healthy volunteers were told that an inert cream, applied on the right hand, would increase the laser pain and LEP amplitude to right hand stimulation. They were randomly assigned to either "verbal session" or "conditioning session". In the "verbal session", LEPs to both right and left hand stimulation were recorded at the same intensity before (baseline) and after cream application. In the "conditioning session", after an initial cream application the laser stimulus intensity was increased surreptitiously to make the subjects believe that the treatment really increased the pain sensation. Then, the cream was reapplied, and LEPs were recorded at the same stimulus intensity as at the baseline. It was found that the verbal suggestion to feel more pain disrupted the physiological habituation of the laser-pain rating and LEP amplitude to treated (right) hand stimulation. Unlike previously demonstrated for the placebo effect, the learning did not potentiate the nocebo effect.

  7. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays

    NASA Astrophysics Data System (ADS)

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-05-01

    Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz-10 kHz. The needles can penetrate into the whisker barrel area of a rat's cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology.

  8. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    SciTech Connect

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  9. Action prediction based on anticipatory brain potentials during simulated driving

    NASA Astrophysics Data System (ADS)

    Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R.

    2015-12-01

    Objective. The ability of an automobile to infer the driver’s upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver’s intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. Approach. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by ‘Start’/‘Stop’ cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. Main results. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a ‘Red’ traffic light) versus events that do not require such action (No-go condition; e.g. a ‘Yellow’ light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. Significance. We show for the first time the feasibility of predicting the driver’s intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

  10. Action potential and contraction of Dionaea muscipula (Venus flytrap).

    PubMed

    DI PALMA, J R; MOHL, R; BEST, W

    1961-03-24

    Observation of the action potential and contraction of the leaf of Dionaea muscipula Ellis revealed several interesting phenomena. Two successive stimuli are generally necessary to cause contraction. The first and ineffective stimulus is associated with slow depolarization. The second stimulus has much more rapid depolarization and initiates contraction.

  11. Passive Responses Resembling Action Potentials: A Device for the Classroom

    ERIC Educational Resources Information Center

    Newman, Ian A.; Pickard, Barbara G.

    1975-01-01

    Describes the construction and operation of a network of entirely passive electrical components that gives a response to an electrical shock similar to an action potential. The network of resistors, capacitors, and diodes was developed to produce responses that would mimic those observed, for example, when a dark-grown pea epicotyl is shocked…

  12. Propagation of Action Potentials: An Active Participation Exercise.

    ERIC Educational Resources Information Center

    Felsten, Gary

    1998-01-01

    Describes an active participation exercise that demonstrates the propagation of action potentials (the ability to transmit information through the neural network, dependent upon chemical interactions in the brain). Students assume the structure and function of the network by lining up around the room and communicating through hand signals and…

  13. Sodium and potassium conductance changes during a membrane action potential

    PubMed Central

    Bezanilla, Francisco; Rojas, Eduardo; Taylor, Robert E.

    1970-01-01

    1. A method for turning a membrane potential control system on and off in less than 10 μsec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential. 2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential. 3. The total membrane conductance taken from these current—voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939). 4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin—Huxley equations. 5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential. PMID:5505231

  14. Spatial variation of compound muscle action potentials across human gastrocnemius medialis.

    PubMed

    Vieira, Taian M; Botter, Alberto; Minetto, Marco A; Hodson-Tole, Emma F

    2015-09-01

    The massed action potential (M wave) elicited through nerve stimulation underpins a wide range of physiological and mechanical understanding of skeletal muscle structure and function. Although systematic approaches have evaluated the effect of different factors on M waves, the effect of the location and distribution of activated fibers within the muscle remains unknown. By detecting M waves from the medial gastrocnemius (MG) of 12 participants with a grid of 128 electrodes, we investigated whether different populations of muscle units have different spatial organization within MG. If populations of muscle units occupy discrete MG regions, current pulses of progressively greater intensities applied to the MG nerve branch would be expected to lead to local changes in M-wave amplitudes. Electrical pulses were therefore delivered at 2 pps, with the current pulse amplitude increased every 10 stimuli to elicit different degrees of muscle activation. The localization of MG response to increases in current intensity was determined from the spatial distribution of M-wave amplitude. Key results revealed that increases in M-wave amplitude were detected somewhat locally, by 10-50% of the 128 electrodes. Most importantly, the electrodes detecting greatest increases in M-wave amplitude were localized at different regions in the grid, with a tendency for greater stimulation intensities to elicit M waves in the more distal MG region. The presented results indicate that M waves recorded locally may not provide a representative MG response, with major implications for the estimation of, e.g., the maximal stimulation levels, the number of motor units, and the onset and normalization in H-reflex studies.

  15. The effects of heart rate on the action potential of guinea-pig and human ventricular muscle.

    PubMed

    Attwell, D; Cohen, I; Eisner, D A

    1981-01-01

    1. On increasing the stimulation frequency of isolated pieces of guinea-pig ventricular muscle, the resting potential depolarizes, and the action potential duration and amplitude are reduced. On termination of the high frequency train of action potentials, these changes are reversed. 2. The resting potential changes are roughly exponential, with a time constant of the order of 10 sec, and are attributable to K+ accumulation in the extracellular space. They are not explicable in terms of known gating variables. 3. The action potential duration and amplitude recover much more slowly than the resting potential, after a high frequency train (half-time approximately 5 min). The time course of these recoveries is not exponential, and is slower after trains which produce more shortening of the action potential. The slow time course suggests that K+ accumulation is not the main cause of the changes in action potential shape. Furthermore, when a certain depolarization of the resting potential is produced by a high frequency train, there is a greater reduction of the action potential duration than that which occurs when the bathing [K+] is raised to produce the same depolarization (Reiter & Stickel, 1968). This is so even when a gradient of extracellular [K+] is induced in the preparation, to mimic non-uniform K+ accumulation. 4. Similarly, the shortening of the action potential produced by toxic doses or cardiotonic steroids is probably not the result of K+ accumulation. 5. The slow changes of the action potential shape produced by a high frequency train are not attributable to the effects of gating variables, nor (solely) to a rise in the intracellular Na concentration stimulating the electrogenic Na/K pump. The dye 3,3'-diethylthiadicarbocyanine, which blocks the Ca2+-activated K conductance in the erythrocyte, has no significant effect on the shape changes. 6. After a sudden change in heart rate, the QT interval of the human electrocardiogram (e.c.g.) changes slowly to a

  16. Focused ultrasound effects on nerve action potential in vitro

    PubMed Central

    Colucci, Vincent; Strichartz, Gary; Jolesz, Ferenc; Vykhodtseva, Natalia; Hynynen, Kullervo

    2009-01-01

    Minimally invasive applications of thermal and mechanical energy to selective areas of the human anatomy have led to significant advances in treatment of and recovery from typical surgical interventions. Image-guided focused ultrasound allows energy to be deposited deep into the tissue, completely noninvasively. There has long been interest in using this focal energy delivery to block nerve conduction for pain control and local anesthesia. In this study, we have performed an in vitro study to further extend our knowledge of this potential clinical application. The sciatic nerves from the bullfrog (Rana catesbeiana) were subjected to focused ultrasound (at frequencies of 0.661MHz and 1.986MHz) and to heated Ringer’s solution. The nerve action potential was shown to decrease in the experiments and correlated with temperature elevation measured in the nerve. The action potential recovered either completely, partially, or not at all, depending on the parameters of the ultrasound exposure. The reduction of the baseline nerve temperature by circulating cooling fluid through the sonication chamber did not prevent the collapse of the nerve action potential; but higher power was required to induce the same endpoint as without cooling. These results indicate that a thermal mechanism of focused ultrasound can be used to block nerve conduction, either temporarily or permanently. PMID:19647923

  17. [The effect of the transmembrane potential level on the dynamic extinction of the amplitude of the synaptic reactions in the snail under potential-fixation conditions].

    PubMed

    Gusev, P V

    1995-01-01

    The goal of this work was to describe a contribution of postsynaptic membrane in synaptic plasticity. To solve this problem the influence of the level of transmembrane potential on the dynamics of transmembrane synaptic current amplitude was studied during rhythmical stimulation of the nerve. It was shown that with increase of transmembrane potential value the slope of the function of transmembrane current decrease became steeper. It was also shown that with higher stimulation frequency the influence of transmembrane holding potential upon the dynamics of synaptic reaction increased. The data obtained can be considered as an evidence to the contribution of postsynaptic membrane in synaptic plasticity.

  18. Treating Cancer with Amplitude-Modulated Electromagnetic Fields: A Potential Paradigm Shift, Again?

    EPA Science Inventory

    The Zimmerman et al. (2011) study published here, coupled with the group's two preceding papers (Barbault et al. (2009), Costa et al. (2011)), identify a potential modality for treating tumors at a dramatic reduction in trauma and cost. This set of clinical and explanatory labora...

  19. Modelling in vivo action potential propagation along a giant axon.

    PubMed

    George, Stuart; Foster, Jamie M; Richardson, Giles

    2015-01-01

    A partial differential equation model for the three-dimensional current flow in an excitable, unmyelinated axon is considered. Where the axon radius is significantly below a critical value R(crit) (that depends upon intra- and extra-cellular conductivity and ion channel conductance) the resistance of the intracellular space is significantly higher than that of the extracellular space, such that the potential outside the axon is uniformly small whilst the intracellular potential is approximated by the transmembrane potential. In turn, since the current flow is predominantly axial, it can be shown that the transmembrane potential is approximated by a solution to the one-dimensional cable equation. It is noted that the radius of the squid giant axon, investigated by (Hodgkin and Huxley 1952e), lies close to R(crit). This motivates us to apply the three-dimensional model to the squid giant axon and compare the results thus found to those obtained using the cable equation. In the context of the in vitro experiments conducted in (Hodgkin and Huxley 1952e) we find only a small difference between the wave profiles determined using these two different approaches and little difference between the speeds of action potential propagation predicted. This suggests that the cable equation approximation is accurate in this scenario. However when applied to the it in vivo setting, in which the conductivity of the surrounding tissue is considerably lower than that of the axoplasm, there are marked differences in both wave profile and speed of action potential propagation calculated using the two approaches. In particular, the cable equation significantly over predicts the increase in the velocity of propagation as axon radius increases. The consequences of these results are discussed in terms of the evolutionary costs associated with increasing the speed of action potential propagation by increasing axon radius.

  20. Compound muscle action potential cartography of an accessory peroneal nerve.

    PubMed

    Van Dijk, J G; Van der Hoeven, B J

    1998-10-01

    In daily practice, accessory peroneal nerves (APNs) are detected in less than the 18-25% of legs, as revealed by systematic searches. In one APN case, compound muscle action potential cartography showed that the APN was only apparent when the recording electrode was placed over a small lateral region of the extensor digitorum brevis muscle. Effects of recording site can explain why many APNs go unrecognized.

  1. Potentiation of antitumor drug action by centrophenoxine: specificity.

    PubMed

    Sladek, N E

    1977-05-01

    The cytotoxic action of certain antitumor agents is potentiated by centrophenoxine although centrophenoxine itself is not an antitumor agent. Previous investigations have suggested that centrophenoxine might potentiate the cytotoxicity produced by antitumor drugs that alkylate, and other modalities that damage, DNA, but that it would not potentiate the cytotoxicity produced by antitumor drugs that inflict cellular damage in other ways. To test this hypothesis, the antitumor effects of X-irradiation UV-irradiation, alkylating agents and antitumor drugs that are not ordinarily considered to be alkylating agents were determined in the presence and absence of centrophenoxine. Mouse P388 lymphoma cells growing in static suspension culture were used as the experimental tumor. The cytotoxic action of most alkylating agents was found to be potentiated by centrophenoxine; Included in this group were several difunctional nitrogen mustards, two ethylenimines, a nitrosourea and mitomycin C. Greatest enhancement, 7-fold, was of chlorambucil antitumor activity. Centrophenoxine did not potentiate the lethality of X- or UV-irradiation or the cytotoxicity of several antineoplastic drugs that are not alkylating agents.

  2. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties

    PubMed Central

    Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry

    2015-01-01

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca2+-activated K+ channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. SIGNIFICANCE STATEMENT Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons

  3. Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.

    PubMed

    Arnold, W David; Sheth, Kajri A; Wier, Christopher G; Kissel, John T; Burghes, Arthur H; Kolb, Stephen J

    2015-09-25

    Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons.

  4. Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.

    PubMed

    Arnold, W David; Sheth, Kajri A; Wier, Christopher G; Kissel, John T; Burghes, Arthur H; Kolb, Stephen J

    2015-01-01

    Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons. PMID:26436455

  5. Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles

    PubMed Central

    Arnold, W. David; Sheth, Kajri A.; Wier, Christopher G.; Kissel, John T.; Burghes, Arthur H.; Kolb, Stephen J.

    2015-01-01

    Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons. PMID:26436455

  6. Effect of width, amplitude and position of a CMB hot spot on core convection and dynamo action

    NASA Astrophysics Data System (ADS)

    Dietrich, W.; Wicht, J.; Hori, K.

    2015-10-01

    Within the fluid iron cores of terrestrial planets, convection and hence the generation of global magnetic fields are controlled by the overlying rocky mantle. The thermal structure of the lower mantle determines how much heat is allowed to escape the core. Hot lower mantle features, like the thermal footprint of a giant impact or hot mantle plumes will reduce locally the heat flux through the core mantle boundary (CMB) and thereby weaken core convection and affect the magnetic field generation process. In this study, we numerically investigate how parametrised hot spots at the CMB with arbitrary size, amplitude and position affect core convection and hence the dynamo. The effect of the heat flux anomaly is quantified by changes in global flow symmetry properties, such as the emergence of equatorial antisymmetric and axisymmetric (EAA) zonal flows. For pure hydrodynamic models the EAA symmetry scales almost linearly with its respective amplitude and size, whereas self-consistent dynamo simulations typically either suppress or drastically enhance EAA depending mainly on the length scale of the heat flux anomaly. Our results suggest, that the horizontal extent of the anomaly should be on the order of the outer core radius to significantly affect flow and field symmetries. As an implication to Mars, the study concludes that an ancient core field modified by a CMB heat flux anomaly is not able to heteroge- neously magnetise the crust to the present-day level of north-south asymmetry.

  7. Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles-a TMS Study.

    PubMed

    Sale, Martin V; Rogasch, Nigel C; Nordstrom, Michael A

    2016-01-01

    The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs.

  8. Effect of width, amplitude, and position of a core mantle boundary hot spot on core convection and dynamo action

    NASA Astrophysics Data System (ADS)

    Dietrich, Wieland; Wicht, Johannes; Hori, Kumiko

    2015-12-01

    Within the fluid iron cores of terrestrial planets, convection and the resulting generation of global magnetic fields are controlled by the overlying rocky mantle. The thermal structure of the lower mantle determines how much heat is allowed to escape the core. Hot lower mantle features, such as the thermal footprint of a giant impact or hot mantle plumes, will locally reduce the heat flux through the core mantle boundary (CMB), thereby weakening core convection and affecting the magnetic field generation process. In this study, we numerically investigate how parametrised hot spots at the CMB with arbitrary sizes, amplitudes, and positions affect core convection and hence the dynamo. The effect of the heat flux anomaly is quantified by changes in global flow symmetry properties, such as the emergence of equatorial antisymmetric, axisymmetric (EAA) zonal flows. For purely hydrodynamic models, the EAA symmetry scales almost linearly with the CMB amplitude and size, whereas self-consistent dynamo simulations typically reveal either suppressed or drastically enhanced EAA symmetry depending mainly on the horizontal extent of the heat flux anomaly. Our results suggest that the length scale of the anomaly should be on the same order as the outer core radius to significantly affect flow and field symmetries. As an implication to Mars and in the range of our model, the study concludes that an ancient core field modified by a CMB heat flux anomaly is not able to heterogeneously magnetise the crust to the present-day level of north-south asymmetry on Mars. The resulting magnetic fields obtained using our model either are not asymmetric enough or, when they are asymmetric enough, show rapid polarity inversions, which are incompatible with thick unidirectional magnetisation.

  9. Sural sensory nerve action potential: A study in healthy Indian subjects

    PubMed Central

    Sreenivasan, Aarthika; Mansukhani, Khushnuma A; Sharma, Alika; Balakrishnan, Lajita

    2016-01-01

    Background: The sural sensory nerve action potential (SNAP) is an important electrodiagnostic study for suspected peripheral neuropathies. Incorrect technique and unavailability of reference data can lead to erroneous conclusions. Objectives: To establish reference data for sural SNAP in age-stratified healthy subjects at three sites of stimulation. Materials and Methods: A prospective study was conducted in 146 nerves from healthy subjects aged between 18 years and 90 years, stratified into six age groups (a = 18-30 years, b = 31–40 years, c = 41–50 years, d = 51–60 years, e = 61–70 years, and f >71 years). Sural SNAP was recorded antidromically, stimulating at three sites at distances of 14 cm, 12 cm, and 10 cm from the recording electrode. Mean – 2 standard deviation (SD) of the transformed data was used to generate reference values for amplitudes. Analysis of variance (ANOVA) test was used for inter-group and between three sites comparisons of amplitudes. Results: The lower limits of amplitude at 14 cm were 12.4 μV, 10.4 μV, 6.5 μV, 5.3 μV, 2.9 μV, and 1.9 μV; at 12 cm were 13.5 μV, 13.6 μV, 8.5 μV, 7.8 μV, 3.5 μV, and 2.8 μV; and at 10 cm were 16.3 μV, 16.3 μV, 11.1 μV, 10.0 μV, 4.8 μV, and 3.7 μV for groups a, b, c, d, e, and f, respectively. A statistically significant difference in amplitudes was noted from the three different sites of stimulation (P < 0.001). The amplitude differed significantly above the age of 60 years (P < 0.01) but not between groups e and f (P > 0.05). Conclusion: This study provides reference data for sural SNAP in Indian population at three different sites of stimulation along the calf in six age groups. It also shows significant variation in amplitude from the three different sites of stimulation. PMID:27570380

  10. Atrial action potential heterogeneity measured by unipolar electrograms.

    PubMed

    Vigmond, Edward J; Tsoi, Vincent; Pagé, Pierre

    2006-01-01

    Vagally-induced action potential duration (APD) heterogeneity can lead to the breakdown of atrial flutter into fibrillation. The exact distribution of vagal mediated effects in the atria is unknown, however. This study analyzed canine electrograms in order to determine changes in APD. Electrograms were recorded under control, and left and right vagal nerve stimulation. Simulations in a computer model were first performed in order to determine how local acetylcholine concentrations affect electrograms. Two measures were investigated to assess APD changes. Results indicate that APD is reduced nonuniformly, and contralateral effects were seen.

  11. Influence of the Dirac-Hartree-Fock starting potential on the parity-nonconserving electric-dipole-transition amplitudes in cesium and thallium

    NASA Technical Reports Server (NTRS)

    Perger, W. F.; Das, B. P.

    1987-01-01

    The parity-nonconserving electric-dipole-transition amplitudes for the 6s1/2-7s1/2 transition in cesium and the 6p1/2-7p1/2 transition in thallium have been calculated by the Dirac-Hartree-Fock method. The effects of using different Dirac-Hartree-Fock atomic core potentials are examined and the transition amplitudes for both the length and velocity gauges are given. It is found that the parity-nonconserving transition amplitudes exhibit a greater dependence on the starting potential for thallium than for cesium.

  12. Compound Muscle Action Potential and Motor Function in Children with Spinal Muscular Atrophy

    PubMed Central

    Lewelt, Aga J.; Krosschell, Kristin J.; Scott, Charles; Sakonju, Ai; Kissel, John T.; Crawford, Thomas O.; Acsadi, Gyula; D'Anjou, Guy; Elsheikh, Bakri; Reyna, Sandra P.; Schroth, Mary K.; Maczulski, Jo Anne; Stoddard, Gregory J.; Elovic, Elie; Swoboda, Kathryn J.

    2010-01-01

    Introduction Reliable outcome measures that reflect the underlying disease process and correlate with motor function in children with SMA are needed for clinical trials. Methods Maximum ulnar compound muscle action potential (CMAP) data were collected at 2 visits over a 4–6 week period in children with SMA types II and III, ages 2–17 years old, at 4 academic centers. Primary functional outcome measures included the Modified Hammersmith Functional Motor Scale (MHFMS) and MHFMS-Extend. Results CMAP negative peak amplitude and area showed excellent discrimination between the ambulatory and non-ambulatory SMA cohorts (ROC=0.88). CMAP had excellent test-retest reliability (ICC=0.96–0.97, n=64) and moderate to strong correlation with the MHFMS and MHFMS-Extend (r=0.61–0.73, n=68, p<0.001). Discussion Maximum ulnar CMAP amplitude and area is a feasible, valid and reliable outcome measure for use in pediatric multicenter clinical trials in SMA. CMAP correlates well with motor function and has potential value as a relevant surrogate for disease status. PMID:20737553

  13. Electrophysiological aspects of sensory conduction velocity in healthy adults. 2. Ratio between the amplitude of sensory evoked potentials at the wrist on stimulating different fingers in both hands.

    PubMed Central

    Cruz Martínez, A; Barrio, M; Pérez Conde, M C; Ferrer, M T

    1978-01-01

    The normal ratio between the amplitude of the sensory evoked potential (SEP) at the wrist on stimulating digits 1, 2, 3, and 5 was determined in 44 healthy adult subjects. The first digit had the larger amplitude, and the fifth digit the smallest SEP. The amplitude expresses the density of sensory innervation in each finger. The ratio between the amplitude of different fingers varied according to the age of the subject. The amplitude of the SEP from a digit innervated by the median nerve decreased in the elderly more than the SEP amplitude of the digit innervated by the ulnar nerve, probably because of a chronic compression in the carpal tunnel. The changes in the normal amplitude ratio can be applied to the topographic diagnosis of radicular and brachial plexus lesions if a fixed segmental sensory innervation of the hand is accepted. In 44 right handed subjects the amplitude of the sensory evoked potentials at the wrist was significantly larger in the left hand. This asymmetry of sensory innervation between hands could be physiological, and suggests a greater density of sensory innervation in the left hand of right handed subjects. PMID:731255

  14. A web portal for in-silico action potential predictions

    PubMed Central

    Williams, Geoff; Mirams, Gary R.

    2015-01-01

    Introduction Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way of predicting the integrated compound effects on whole-cell electrophysiology, to provide an improved indication of pro-arrhythmic risk. Methods We have developed open source software to run cardiac electrophysiology simulations to predict the overall effect of compounds that block IKr, ICaL, INa, IKs, IK1 and Ito to varying degrees, using a choice of mathematical electrophysiology models. To enable safety pharmacology teams to run and evaluate these simulations easily, we have also developed an open source web portal interface to this simulator. Results The web portal can be found at https://chaste.cs.ox.ac.uk/ActionPotential. Users can enter details of compound affinities for ion channels in the form of IC50 or pIC50 values, run simulations, store the results for later retrieval, view summary graphs of the results, and export data to a spreadsheet format. Discussion This web portal provides a simple interface to reference versions of mathematical models, and well-tested state-of-the-art equation solvers. It provides safety teams easy access to the emerging technology of cardiac electrophysiology simulations for use in the drug-discovery process. PMID:25963830

  15. Flexible graphene transistors for recording cell action potentials

    NASA Astrophysics Data System (ADS)

    Blaschke, Benno M.; Lottner, Martin; Drieschner, Simon; Bonaccini Calia, Andrea; Stoiber, Karolina; Rousseau, Lionel; Lissourges, Gaëlle; Garrido, Jose A.

    2016-06-01

    Graphene solution-gated field-effect transistors (SGFETs) are a promising platform for the recording of cell action potentials due to the intrinsic high signal amplification of graphene transistors. In addition, graphene technology fulfills important key requirements for in-vivo applications, such as biocompability, mechanical flexibility, as well as ease of high density integration. In this paper we demonstrate the fabrication of flexible arrays of graphene SGFETs on polyimide, a biocompatible polymeric substrate. We investigate the transistor’s transconductance and intrinsic electronic noise which are key parameters for the device sensitivity, confirming that the obtained values are comparable to those of rigid graphene SGFETs. Furthermore, we show that the devices do not degrade during repeated bending and the transconductance, governed by the electronic properties of graphene, is unaffected by bending. After cell culture, we demonstrate the recording of cell action potentials from cardiomyocyte-like cells with a high signal-to-noise ratio that is higher or comparable to competing state of the art technologies. Our results highlight the great capabilities of flexible graphene SGFETs in bioelectronics, providing a solid foundation for in-vivo experiments and, eventually, for graphene-based neuroprosthetics.

  16. In-vitro characterization of a cochlear implant system for recording of evoked compound action potentials

    PubMed Central

    2012-01-01

    Background Modern cochlear implants have integrated recording systems for measuring electrically evoked compound action potentials of the auditory nerve. The characterization of such recording systems is important for establishing a reliable basis for the interpretation of signals acquired in vivo. In this study we investigated the characteristics of the recording system integrated into the MED-EL PULSARCI100 cochlear implant, especially its linearity and resolution, in order to develop a mathematical model describing the recording system. Methods In-vitro setup: The cochlear implant, including all attached electrodes, was fixed in a tank of physiologic saline solution. Sinusoidal signals of the same frequency but with different amplitudes were delivered via a signal generator for measuring and recording on a single electrode. Computer simulations: A basic mathematical model including the main elements of the recording system, i.e. amplification and digitalization stage, was developed. For this, digital output for sinusoidal input signals of different amplitudes were calculated using in-vitro recordings as reference. Results Using an averaging of 100 measurements the recording system behaved linearly down to approximately -60 dB of the input signal range. Using the same method, a system resolution of 10 μV was determined for sinusoidal signals. The simulation results were in very good agreement with the results obtained from in-vitro experiments. Conclusions The recording system implemented in the MED-EL PULSARCI100 cochlear implant for measuring the evoked compound action potential of the auditory nerve operates reliably. The developed mathematical model provides a good approximation of the recording system. PMID:22531599

  17. The Potential of Deweyan-Inspired Action Research

    ERIC Educational Resources Information Center

    Stark, Jody L.

    2014-01-01

    In its broadest sense, pragmatism could be said to be the philosophical orientation of all action research. Action research is characterized by research, action, and participation grounded in democratic principles and guided by the aim of social improvement. Furthermore, action research is an active process of inquiry that does not admit…

  18. Cardiac dynamics: a simplified model for action potential propagation

    PubMed Central

    2012-01-01

    This paper analyzes a new semiphysiological ionic model, used recently to study reexitations and reentry in cardiac tissue [I.R. Cantalapiedra et al, PRE 82 011907 (2010)]. The aim of the model is to reproduce action potencial morphologies and restitution curves obtained, either from experimental data, or from more complex electrophysiological models. The model divides all ion currents into four groups according to their function, thus resulting into fast-slow and inward-outward currents. We show that this simplified model is flexible enough as to accurately capture the electrical properties of cardiac myocytes, having the advantage of being less computational demanding than detailed electrophysiological models. Under some conditions, it has been shown to be amenable to mathematical analysis. The model reproduces the action potential (AP) change with stimulation rate observed both experimentally and in realistic models of healthy human and guinea pig myocytes (TNNP and LRd models, respectively). When simulated in a cable it also gives the right dependence of the conduction velocity (CV) with stimulation rate. Besides reproducing correctly these restitution properties, it also gives a good fit for the morphology of the AP, including the notch typical of phase 1. Finally, we perform simulations in a realistic geometric model of the rabbit’s ventricles, finding a good qualitative agreement in AP propagation and the ECG. Thus, this simplified model represents an alternative to more complex models when studying instabilities in wave propagation. PMID:23194429

  19. Frontoxins, three-finger toxins from Micrurus frontalis venom, decrease miniature endplate potential amplitude at frog neuromuscular junction.

    PubMed

    Moreira, K G; Prates, M V; Andrade, F A C; Silva, L P; Beirão, P S L; Kushmerick, C; Naves, L A; Bloch, C

    2010-08-01

    Neurotoxicity is a major symptom of envenomation caused by Brazilian coral snake Micrurus frontalis. Due to the small amount of material that can be collected, no neurotoxin has been fully sequenced from this venom. In this work we report six new three-finger like toxins isolated from the venom of the coral snake M. frontalis which we named Frontoxin (FTx) I-VI. Toxins were purified using multiple steps of RP-HPLC. Molecular masses were determined by MALDI-TOF and ESI ion-trap mass spectrometry. The complete amino acid sequence of FTx II, III, IV and V were determined by sequencing of overlapping proteolytic fragments by Edman degradation and by de novo sequencing. The amino acid sequences of FTx I, II, III and VI predict 4 conserved disulphide bonds and structural similarity to previously reported short-chain alpha-neurotoxins. FTx IV and V each contained 10 conserved cysteines and share high similarity with long-chain alpha-neurotoxins. At the frog neuromuscular junction FTx II, III and IV reduced miniature endplate potential amplitudes in a time-and concentration-dependent manner suggesting Frontoxins block nicotinic acetylcholine receptors.

  20. Potential anti-inflammatory actions of the elmiric (lipoamino) acids

    PubMed Central

    Burstein, Sumner H.; Adams, Jeffrey K.; Bradshaw, Heather B.; Fraioli, Cristian; Rossetti, Ronald G.; Salmonsen, Rebecca A.; Shaw, John W.; Walker, J. Michael; Zipkin, Robert E.; Zurier, Robert B.

    2007-01-01

    A library of amino acid-fatty acid conjugates (elmiric acids) was synthesized and evaluated for activity as potential anti-inflammatory agents. The compounds were tested in vitro for their effects on cell proliferation and prostaglandin production and compared with their effects on in vivo models of inflammation. LPS stimulated RAW 267.4 mouse macrophage cells was the in vitro model and phorbol ester-induced mouse ear edema served as the principal in vivo model. The prostaglandin responses were found to be strongly dependent on the nature of the fatty acid part of the molecule. Polyunsaturated acid conjugates produced a marked increase in media levels of i15-deoxy-PGJ2 with minimal effects on PGE production. It is reported in the literature that prostaglandin ratios in which the J series predominates over the E series promote the resolution of inflammatory conditions. Several of the elmiric acids tested here produced such favorable ratios suggesting that their potential anti-inflammatory activity occurs via a novel mechanism of action. The ear edema assay results were generally in agreement with the prostaglandin assay findings indicating a connection between them. PMID:17383881

  1. Quantitative Assessment of the Distributions of Membrane Conductances Involved in Action Potential Backpropagation Along Basal Dendrites

    PubMed Central

    Acker, Corey D.; Antic, Srdjan D.

    2009-01-01

    Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites is therefore likely to play an important role in cortical information processing. Both synaptic integration and synaptic plasticity depend crucially on dendritic membrane excitability and the backpropagation of action potentials. We carried out multisite voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium, or Ih conductance had little effect on dendritic AP propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a nonuniform sodium channel distribution with decreasing conductance with distance from the soma, together with a nonuniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high-frequency trains of APs and the local generation of sodium spikelets. We also explored the conditions under which IA down-regulation would produce branch strength potentiation in the proposed model. Finally, we discuss the hypothesis that a fraction of basal branches may have different membrane properties compared with sister branches in the same dendritic tree. PMID:19118105

  2. Generation of slow wave type action potentials in the mouse small intestine involves a non-L-type calcium channel.

    PubMed

    Malysz, J; Richardson, D; Farraway, L; Christen, M O; Huizinga, J D

    1995-10-01

    Intrinsic electrical activities in various isolated segments of the mouse small intestine were recorded (i) to characterize action potential generation and (ii) to obtain a profile on the ion channels involved in initiating the slow wave type action potentials (slow waves). Gradients in slow wave frequency, resting membrane potential, and occurrence of spiking activity were found, with the proximal intestine exhibiting the highest frequency, the most hyperpolarized cell membrane, and the greatest occurrence of spikes. The slow waves were only partially sensitive to L-type calcium channel blockers. Nifedipine, verapamil, and pinaverium bromide abolished spikes that occurred on the plateau phase of the slow waves in all tissues. The activity that remained in the presence of L-type calcium channel blockers, the upstroke potential, retained a similar amplitude to the original slow wave and was of identical frequency. The upstroke potential was not sensitive to a reduction in extracellular chloride or to the sodium channel blockers tetrodotoxin and mexiletine. Abolishment of the Na+ gradient by removal of 120 mM extracellular Na+ reduced the upstroke potential frequency by 13 - 18% and its amplitude by 50 - 70% in the ileum. The amplitude was similarly reduced by Ni2+ (up to 5 mM), and by flufenamic acid (100 mu M), a nonspecific cation and chloride channel blocker. Gadolinium, a nonspecific blocker of cation and stretch-activated channels, had no effect. Throughout these pharmacological manipulations, a robust oscillation remained at 5 - 10 mV. This oscillation likely reflects pacemaker activity. It was rapidly abolished by removal of extracellular calcium but not affected by L-type calcium channel blockers. In summary, the mouse small intestine has been established as a model for research into slow wave generation and electrical pacemaker activity. The upstroke part of the slow wave has two components, the pacemaker component involves a non-L-type calcium channel

  3. Movement-Related Cortical Potential Amplitude Reduction after Cycling Exercise Relates to the Extent of Neuromuscular Fatigue.

    PubMed

    Spring, Jérôme Nicolas; Place, Nicolas; Borrani, Fabio; Kayser, Bengt; Barral, Jérôme

    2016-01-01

    Exercise-induced fatigue affects the motor control and the ability to generate a given force or power. Surface electroencephalography allows researchers to investigate movement-related cortical potentials (MRCP), which reflect preparatory brain activity 1.5 s before movement onset. Although the MRCP amplitude appears to increase after repetitive single-joint contractions, the effects of large-muscle group dynamic exercise on such pre-motor potential remain to be described. Sixteen volunteers exercised 30 min at 60% of the maximal aerobic power on a cycle ergometer, followed by a 10-km all-out time trial. Before and after each of these tasks, knee extensor neuromuscular function was investigated using maximal voluntary contractions (MVC) combined with electrical stimulations of the femoral nerve. MRCP was recorded during 60 knee extensions after each neuromuscular sequence. The exercise resulted in a significant decrease in the knee extensor MVC force after the 30-min exercise (-10 ± 8%) and the time trial (-21 ± 9%). The voluntary activation level (VAL; -6 ± 8 and -12 ± 10%), peak twitch (Pt; -21 ± 16 and -32 ± 17%), and paired stimuli (P100 Hz; -7 ± 11 and -12 ± 13%) were also significantly reduced after the 30-min exercise and the time trial. The first exercise was followed by a decrease in the MRCP, mainly above the mean activity measured at electrodes FC1-FC2, whereas the reduction observed after the time trial was related to the FC1-FC2 and C2 electrodes. After both exercises, the reduction in the late MRCP component above FC1-FC2 was significantly correlated with the reduction in P100 Hz (r = 0.61), and the reduction in the same component above C2 was significantly correlated with the reduction in VAL (r = 0.64). In conclusion, large-muscle group exercise induced a reduction in pre-motor potential, which was related to muscle alterations and resulted in the inability to produce a maximal voluntary contraction. PMID:27313522

  4. Movement-Related Cortical Potential Amplitude Reduction after Cycling Exercise Relates to the Extent of Neuromuscular Fatigue

    PubMed Central

    Spring, Jérôme Nicolas; Place, Nicolas; Borrani, Fabio; Kayser, Bengt; Barral, Jérôme

    2016-01-01

    Exercise-induced fatigue affects the motor control and the ability to generate a given force or power. Surface electroencephalography allows researchers to investigate movement-related cortical potentials (MRCP), which reflect preparatory brain activity 1.5 s before movement onset. Although the MRCP amplitude appears to increase after repetitive single-joint contractions, the effects of large-muscle group dynamic exercise on such pre-motor potential remain to be described. Sixteen volunteers exercised 30 min at 60% of the maximal aerobic power on a cycle ergometer, followed by a 10-km all-out time trial. Before and after each of these tasks, knee extensor neuromuscular function was investigated using maximal voluntary contractions (MVC) combined with electrical stimulations of the femoral nerve. MRCP was recorded during 60 knee extensions after each neuromuscular sequence. The exercise resulted in a significant decrease in the knee extensor MVC force after the 30-min exercise (−10 ± 8%) and the time trial (−21 ± 9%). The voluntary activation level (VAL; −6 ± 8 and −12 ± 10%), peak twitch (Pt; −21 ± 16 and −32 ± 17%), and paired stimuli (P100 Hz; −7 ± 11 and −12 ± 13%) were also significantly reduced after the 30-min exercise and the time trial. The first exercise was followed by a decrease in the MRCP, mainly above the mean activity measured at electrodes FC1-FC2, whereas the reduction observed after the time trial was related to the FC1-FC2 and C2 electrodes. After both exercises, the reduction in the late MRCP component above FC1-FC2 was significantly correlated with the reduction in P100 Hz (r = 0.61), and the reduction in the same component above C2 was significantly correlated with the reduction in VAL (r = 0.64). In conclusion, large-muscle group exercise induced a reduction in pre-motor potential, which was related to muscle alterations and resulted in the inability to produce a maximal voluntary contraction. PMID:27313522

  5. Movement-Related Cortical Potential Amplitude Reduction after Cycling Exercise Relates to the Extent of Neuromuscular Fatigue.

    PubMed

    Spring, Jérôme Nicolas; Place, Nicolas; Borrani, Fabio; Kayser, Bengt; Barral, Jérôme

    2016-01-01

    Exercise-induced fatigue affects the motor control and the ability to generate a given force or power. Surface electroencephalography allows researchers to investigate movement-related cortical potentials (MRCP), which reflect preparatory brain activity 1.5 s before movement onset. Although the MRCP amplitude appears to increase after repetitive single-joint contractions, the effects of large-muscle group dynamic exercise on such pre-motor potential remain to be described. Sixteen volunteers exercised 30 min at 60% of the maximal aerobic power on a cycle ergometer, followed by a 10-km all-out time trial. Before and after each of these tasks, knee extensor neuromuscular function was investigated using maximal voluntary contractions (MVC) combined with electrical stimulations of the femoral nerve. MRCP was recorded during 60 knee extensions after each neuromuscular sequence. The exercise resulted in a significant decrease in the knee extensor MVC force after the 30-min exercise (-10 ± 8%) and the time trial (-21 ± 9%). The voluntary activation level (VAL; -6 ± 8 and -12 ± 10%), peak twitch (Pt; -21 ± 16 and -32 ± 17%), and paired stimuli (P100 Hz; -7 ± 11 and -12 ± 13%) were also significantly reduced after the 30-min exercise and the time trial. The first exercise was followed by a decrease in the MRCP, mainly above the mean activity measured at electrodes FC1-FC2, whereas the reduction observed after the time trial was related to the FC1-FC2 and C2 electrodes. After both exercises, the reduction in the late MRCP component above FC1-FC2 was significantly correlated with the reduction in P100 Hz (r = 0.61), and the reduction in the same component above C2 was significantly correlated with the reduction in VAL (r = 0.64). In conclusion, large-muscle group exercise induced a reduction in pre-motor potential, which was related to muscle alterations and resulted in the inability to produce a maximal voluntary contraction.

  6. Modelling Action Potential Generation and Propagation in Fibroblastic Cells

    NASA Astrophysics Data System (ADS)

    Torres, J. J.; Cornelisse, L. N.; Harks, E. G. A.; Theuvenet, A. P. R.; Ypey, D. L.

    2003-04-01

    Using a standard Hodgkin-Huxley (HH) formalism, we present a mathematical model for action potential (AP) generation and intercellular AP propagation in quiescent (serum-deprived) normal rat kidney (NRK) fibroblasts [1], based on the recent experimental identification of the ion channels involved [2]. The principal ion channels described are those of an inwardly rectifying K+ conductance (GKIR), an L-type calcium conductance (GCaL), an intracellular calcium activated Cl- conductance (GCl(Ca)), a residual leak conductance Gleak, and gap junctional channels between the cells (Ggj). The role of each one of these components in the particular shape of the AP wave-form has been analyzed and compared with experimental observations. In addition, we have studied the role of subcellular processes like intracellular calcium dynamics and calcium buffering in AP generation. AP propagation between cells was reconstructed in a hexagonal model of cells coupled by Ggj with physiological conductance values. The model revealed an excitability mechanism of quiescent NRK cells with a particular role of intracellular calcium dynamics. It allows further explorations of the mechanism of signal generation and transmission in NRK cell cultures and its dependence on growth conditions.

  7. Pharmacological actions of statins: potential utility in COPD.

    PubMed

    Young, R P; Hopkins, R; Eaton, T E

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-κB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-α, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD. PMID:20956147

  8. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    PubMed

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

    2016-06-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement.

  9. Analogue modulation of back-propagating action potentials enables dendritic hybrid signalling

    PubMed Central

    Brunner, János; Szabadics, János

    2016-01-01

    We report that back-propagating action potentials (bAPs) are not simply digital feedback signals in dendrites but also carry analogue information about the overall state of neurons. Analogue information about the somatic membrane potential within a physiological range (from −78 to −64 mV) is retained by bAPs of dentate gyrus granule cells as different repolarization speeds in proximal dendrites and as different peak amplitudes in distal regions. These location-dependent waveform changes are reflected by local calcium influx, leading to proximal enhancement and distal attenuation during somatic hyperpolarization. The functional link between these retention and readout mechanisms of the analogue content of bAPs critically depends on high-voltage-activated, inactivating calcium channels. The hybrid bAP and calcium mechanisms report the phase of physiological somatic voltage fluctuations and modulate long-term synaptic plasticity in distal dendrites. Thus, bAPs are hybrid signals that relay somatic analogue information, which is detected by the dendrites in a location-dependent manner. PMID:27703164

  10. Mathematical model of the neonatal mouse ventricular action potential

    PubMed Central

    Wang, Linda J.; Sobie, Eric A.

    2008-01-01

    Therapies for heart disease are based largely on our understanding of the adult myocardium. The dramatic differences in action potential (AP) shape between neonatal and adult cardiac myocytes, however, indicate that a different set of molecular interactions in neonatal myocytes necessitates different treatment for newborns. Computational modeling is useful for synthesizing data to determine how interactions between components lead to systems-level behavior, but this technique has not been used extensively to study neonatal heart cell function. We created a mathematical model of the neonatal (day 1) mouse myocyte by modifying, based on experimental data, the densities and/or formulations of ion transport mechanisms in an adult cell model. The new model reproduces the characteristic AP shape of neonatal cells, with a brief plateau phase and longer duration than the adult (APD80=60.1 vs. 12.6 ms). The simulation results are consistent with experimental data, including: 1) decreased density, and altered inactivation, of transient outward K+ currents, 2) increased delayed rectifier K+ currents, 3) Ca2+ entry through T-type as well as L-type Ca2+ channels, 4) increased Ca2+ influx through Na+-Ca2+ exchange, and 5) Ca2+ transients resulting from transmembrane Ca2+ entry rather than release from the sarcoplasmic reticulum (SR). Simulations performed with the model generated novel predictions, including increased SR Ca2+ leak and elevated intracellular [Na+] in neonatal compared with adult myocytes. This new model can therefore be used for testing hypotheses and obtaining a better quantitative understanding of differences between neonatal and adult physiology. PMID:18408122

  11. Effect of reduced attention on auditory amplitude-modulation following responses: a study with chirp-evoked potentials.

    PubMed

    Alegre, Manuel; Barbosa, Carla; Valencia, Miguel; Pérez-Alcázar, Marta; Iriarte, Jorge; Artieda, Julio

    2008-02-01

    The amplitude of the auditory amplitude-modulation following responses (AMFR) is variable, depending on the modulation rate. Although 40-Hz responses have higher amplitudes in adults, the AMFR in the 80- to 120-Hz range are less influenced by sleep and more consistent in children. The effect of attention on 40-Hz responses has been addressed in some studies; however, no study to our knowledge has investigated the effect of attention on other stimulation rates. Our aim was to test the effect of attention on the AMFR to different frequencies of stimulation, using a chirp-modulated tone as stimulus. We recorded chirp-evoked responses in 12 subjects while attending to the sound (first condition) and reading a novel (second condition), in a randomly determined sequence. The energy of the response and the intertrial coherence (ITC) were measured by means of time-frequency transforms. The frequency range of response was similar in both conditions. No significant differences were found in the ITC values in the 40-Hz and the 80- to 120-Hz ranges, nor in the energy of the 40-Hz response. The only statistically significant difference found was the lower energy of the response in the 80- to 120-Hz range in the reading condition. Our results suggest that attention may affect auditory steady-state clinical testing using amplitude values. Phase measures may be preferable in this context.

  12. On the impact of examiners on latencies and amplitudes in cervical and ocular vestibular-evoked myogenic potentials evaluated over a large sample (N = 1,038).

    PubMed

    Ertl, Matthias; Boegle, R; Kirsch, V; Dieterich, M

    2016-02-01

    Vestibular-evoked myogenic potentials (VEMPs) are frequently used in the clinical diagnosis and research of vertigo syndromes. Altered latencies or amplitudes are typically interpreted as an indication of disturbance in the processing of vestibular stimuli along the otolithic pathways. Correct interpretation, however, can be difficult as VEMP amplitudes can vary greatly across subjects and across laboratories, likely because they are very sensitive to measurement conditions. Here, we attempted to quantify the impact of examiner differences on VEMP data. We collected data from 1,038 people using eight different experimental examiners, and investigated the effect of examiner on VEMP latencies and amplitudes. We found that the examiner collecting the data had a strong effect on outcome measures with significant differences (p < 0.001) in cVEMP and oVEMP latencies and in oVEMP amplitudes. No significant differences between examiners were found for the cVEMP amplitudes. When we compared the healthy and pathological sides of patients with a clinically diagnosed unilateral disease, no significant differences between sides were found. Given our results and the results reported in the literature, we conclude that the signal features of VEMPs are very sensitive to variables that may be influenced by the examiner. The field should therefore work on a better standard for VEMP recordings.

  13. Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

    ERIC Educational Resources Information Center

    Rodriguez-Falces, Javier

    2015-01-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

  14. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor

    PubMed Central

    Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M.

    2012-01-01

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology1-6. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution1,2. Ideally the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior1,2, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints4,7-9. Field-effect transistors (FETs) can also record electric potentials inside cells10, and since their performance does not depend on impedance11,12, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously we have demonstrated FET-based intracellular recording with kinked nanowire structures10, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here we report a new approach where a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. After penetrating the cell membrane, the SiO2 nanotube brings the cell cytosol into contact with the FET and enables the recording of intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale which is well below that accessible with other methods1,2,4. Studies of cardiomyocyte cells demonstrate that when brought close, the nanotubes of phospholipid-modified BIT-FETs spontaneously penetrate the cell membrane to yield stable, full-amplitude intracellular action

  15. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor.

    PubMed

    Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M

    2012-03-01

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be

  16. Determining electrically evoked compound action potential thresholds: A comparison of computer versus human analysis methods

    PubMed Central

    Glassman, E. Katelyn; Hughes, Michelle L.

    2012-01-01

    Objectives Current cochlear implants (CIs) have telemetry capabilities for measuring the electrically evoked compound action potential (ECAP). Neural Response Telemetry (NRT™; Cochlear) and Neural Response Imaging (NRI; Advanced Bionics [AB]) can measure ECAP responses across a range of stimulus levels to obtain an amplitude growth function. Software-specific algorithms automatically mark the leading negative peak, N1, and the following positive peak/plateau, P2, and apply linear regression to estimate ECAP threshold. Alternatively, clinicians may apply expert judgments to modify the peak markers placed by the software algorithms, and/or use visual detection to identify the lowest level yielding a measurable ECAP response. The goals of this study were to: (1) assess the variability between human and computer decisions for (a) marking N1 and P2, and (b) determination of linear regression threshold (LRT) and visual detection threshold (VDT); and (2) compare LRT and VDT methods within and across human and computer decision methods. Design ECAP amplitude growth functions were measured for three electrodes in each of 20 ears (10 Cochlear Nucleus® 24RE/CI512, and 10 AB CII/90K). LRT, defined as the current level yielding an ECAP with zero amplitude, was calculated for both computer- (C-LRT) and human-picked peaks (H-LRT). VDT, defined as the lowest level resulting in a measurable ECAP response, was also calculated for both computer- (C-VDT) and human-picked peaks (H-VDT). Because NRI assigns peak markers to all waveforms but does not include waveforms with amplitudes less than 20 μV in its regression calculation, C-VDT for AB subjects was defined as the lowest current level yielding an amplitude ≥20 μV. Results Overall, there were significant correlations between human and computer decisions for peak-marker placement, LRT, and VDT for both manufacturers (r = 0.78 to 1.00, p < 0.001). For Cochlear devices, LRT and VDT correlated equally well for both computer- and

  17. An Improved Genetically Encoded Red Fluorescent Ca2+ Indicator for Detecting Optically Evoked Action Potentials

    PubMed Central

    Kobayashi, Chiaki; Ikegaya, Yuji; Nakai, Junichi

    2012-01-01

    Genetically encoded Ca2+ indicators (GECIs) are powerful tools to image activities of defined cell populations. Here, we developed an improved red fluorescent GECI, termed R-CaMP1.07, by mutagenizing R-GECO1. In HeLa cell assays, R-CaMP1.07 exhibited a 1.5–2-fold greater fluorescence response compared to R-GECO1. In hippocampal pyramidal neurons, R-CaMP1.07 detected Ca2+ transients triggered by single action potentials (APs) with a probability of 95% and a signal-to-noise ratio >7 at a frame rate of 50 Hz. The amplitudes of Ca2+ transients linearly correlated with the number of APs. The expression of R-CaMP1.07 did not significantly alter the electrophysiological properties or synaptic activity patterns. The co-expression of R-CaMP1.07 and channelrhodpsin-2 (ChR2), a photosensitive cation channel, in pyramidal neurons demonstrated that R-CaMP1.07 was applicable for the monitoring of Ca2+ transients in response to optically evoked APs, because the excitation light for R-CaMP1.07 hardly activated ChR2. These technical advancements provide a novel strategy for monitoring and manipulating neuronal activity with single cell resolution. PMID:22808076

  18. Mechanisms of action and potential therapeutic uses of thalidomide.

    PubMed

    Mujagić, Hamza; Chabner, Bruce A; Mujagić, Zlata

    2002-06-01

    Thalidomide was first introduced to the market in Germany under the brand name of Contergan in 1956, as a non-barbiturate hypnotic, advocated to ensure a good nights sleep and to prevent morning sickness in pregnancy. It was advertised for its prompt action, lack of hangover, and apparent safety. It has been banned from the market since 1963 after it caused the worldwide teratogenic disaster: babies exposed to thalidomide in utero during the first 34-50 days of pregnancy were born with severe life-threatening birth defects. Despite its unfortunate history, thalidomide has attracted scientific interest again because of its recently discovered action against inflammatory diseases and cancer. Its broad range of biological activities stems from its ability to moderate cytokine action in cancer and inflammatory diseases. Early studies examined its anxiolytic, mild hypnotic, antiemetic, and adjuvant analgesic properties. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy, being superior to Aspirin in controlling leprosy-associated fever. Recent research has shown promising results with thalidomide in patients with myeloma, myelodysplastic syndrome, a variety of infectious diseases, autoimmune diseases, cancer, and progressive body weight loss related to advanced cancer and AIDS. Here we review the history of its development, pharmacokinetics, metabolism, biologic effects, and the results of clinical trials conducted thus far. Further research in this field should be directed towards better understanding of thalidomide metabolism, its mechanism of action, and the development of less toxic and more active analogs. PMID:12035132

  19. Mechanisms of action and potential therapeutic uses of thalidomide.

    PubMed

    Mujagić, Hamza; Chabner, Bruce A; Mujagić, Zlata

    2002-06-01

    Thalidomide was first introduced to the market in Germany under the brand name of Contergan in 1956, as a non-barbiturate hypnotic, advocated to ensure a good nights sleep and to prevent morning sickness in pregnancy. It was advertised for its prompt action, lack of hangover, and apparent safety. It has been banned from the market since 1963 after it caused the worldwide teratogenic disaster: babies exposed to thalidomide in utero during the first 34-50 days of pregnancy were born with severe life-threatening birth defects. Despite its unfortunate history, thalidomide has attracted scientific interest again because of its recently discovered action against inflammatory diseases and cancer. Its broad range of biological activities stems from its ability to moderate cytokine action in cancer and inflammatory diseases. Early studies examined its anxiolytic, mild hypnotic, antiemetic, and adjuvant analgesic properties. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy, being superior to Aspirin in controlling leprosy-associated fever. Recent research has shown promising results with thalidomide in patients with myeloma, myelodysplastic syndrome, a variety of infectious diseases, autoimmune diseases, cancer, and progressive body weight loss related to advanced cancer and AIDS. Here we review the history of its development, pharmacokinetics, metabolism, biologic effects, and the results of clinical trials conducted thus far. Further research in this field should be directed towards better understanding of thalidomide metabolism, its mechanism of action, and the development of less toxic and more active analogs.

  20. Gifted Potential and Poverty: A Call for Extraordinary Action

    ERIC Educational Resources Information Center

    Kitano, Margie K.

    2003-01-01

    Dr. Robinson's proposed action plan will serve the needs of highly achieving gifted students. However, defining giftedness as high academic performance based on traditional assessment procedures could reverse the field's fledgling success in supporting culturally diverse gifted children and youth. Changing the focus of equity in gifted education…

  1. Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.

    PubMed

    Kistamás, Kornél; Hegyi, Bence; Váczi, Krisztina; Horváth, Balázs; Bányász, Tamás; Magyar, János; Szentandrássy, Norbert; Nánási, Péter P

    2015-07-01

    Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.

  2. Potential effects of intrinsic heart pacemaker cell mechanisms on dysrhythmic cardiac action potential firing

    PubMed Central

    Yaniv, Yael; Tsutsui, Kenta; Lakatta, Edward G.

    2015-01-01

    The heart's regular electrical activity is initiated by specialized cardiac pacemaker cells residing in the sinoatrial node. The rate and rhythm of spontaneous action potential firing of sinoatrial node cells are regulated by stochastic mechanisms that determine the level of coupling of chemical to electrical clocks within cardiac pacemaker cells. This coupled-clock system is modulated by autonomic signaling from the brain via neurotransmitter release from the vagus and sympathetic nerves. Abnormalities in brain-heart clock connections or in any molecular clock activity within pacemaker cells lead to abnormalities in the beating rate and rhythm of the pacemaker tissue that initiates the cardiac impulse. Dysfunction of pacemaker tissue can lead to tachy-brady heart rate alternation or exit block that leads to long atrial pauses and increases susceptibility to other cardiac arrhythmia. Here we review evidence for the idea that disturbances in the intrinsic components of pacemaker cells may be implemented in arrhythmia induction in the heart. PMID:25755643

  3. Ionic differences between somatic and axonal action potentials in snail giant neurones

    PubMed Central

    Wald, Flora

    1972-01-01

    1. The ionic requirements of the somatic and axonal action potentials of `H' neurones of the snail Cryptomphallus aspersa were studied using intracellular micro-electrodes. 2. The overshoot of the somatic action potential increased by 10 mV for a tenfold increase in [Ca2+]o. In calcium-free media the action potential decreased gradually to values of 50 to 90% of the control and they could be completely eliminated with 2 mM-EGTA. The maximum rate of rise also varied with [Ca2+]o. 3. After 2 hr in sodium-free solution the somatic action potential decreased 6% in overshoot and 24% in rate of rise. 4. The somatic action potential was not affected by TTX, 5 × 10-6 g/ml. Procaine, 18 mM, reduced its rate of rise but did not eliminate it whereas 30 mM-CoCl2 did. 5. The size of the axonal action potential increased with increased [Na+]o, but decreased with an increase in [Ca2+]o. 6. Procaine, 18 mM, abolished the axonal action potential whereas it was not affected by TTX, 5 × 10-6 g/ml., nor, usually, by 30 mM-CoCl2. 7. The results obtained by studying the compound action potential of the nerves were similar to those from axonal action potentials. 8. The possibility that the somatic action potential is mainly calcium dependent while the axonal action potential is mainly produced by sodium is discussed. PMID:5014099

  4. Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglion neurons.

    PubMed

    Schink, Martin; Leipold, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H

    2016-01-01

    Dorsal root ganglion (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 μM) or low-intensity blue light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8(-/-)), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and, at higher concentrations, progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure. PMID:26383867

  5. Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglion neurons.

    PubMed

    Schink, Martin; Leipold, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H

    2016-01-01

    Dorsal root ganglion (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 μM) or low-intensity blue light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8(-/-)), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and, at higher concentrations, progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure.

  6. A quantitative evaluation of the magnetic field generated by a CA3 pyramidal cell at EPSP and action potential stages.

    PubMed

    Sakatani, Seiichi; Hirose, Akira

    2002-04-01

    We evaluate quantitatively which behavioral stage dominantly generates magnetic field adjacent to a CA3 pyramidal cell by using a compartmental model with dendrites and an axon. Generally speaking, there are four stages in the potential behavior, i.e., excitatory and inhibitory postsynaptic potential, firing action potential, bursting action potential, if any, and after hyperpolarization potential stages. Calculated magnetic field also consists of corresponding four stages. We find, first, the dominant origin of the peaks of the magnetic field is counter propagating pulses at the firing and bursting stage at basal and apical dendrites. Second, the amplitude of the magnetic field changes to a great extent by the cancellation timing of the apical- and basal-originating fields depending on the calcium ionic channel spikes. Third, the field generated by the current flowing through the axon is significant enough when the temporal resolution of the measurement system becomes high. The results predict that the magnetic-field waveform measured in physiological experiments represents the dendritic configurations, channel density distributions, and bursting characteristics. These facts enable new investigations of neuronal activities in more detail through the observation of the magnetic-field waveform.

  7. Nitrous oxide directly inhibits action potential-dependent neurotransmission from single presynaptic boutons adhering to rat hippocampal CA3 neurons.

    PubMed

    Wakita, Masahito; Kotani, Naoki; Yamaga, Toshitaka; Akaike, Norio

    2015-09-01

    We evaluated the effects of N2O on synaptic transmission using a preparation of mechanically dissociated rat hippocampal CA3 neurons that allowed assays of single bouton responses evoked from native functional nerve endings. We studied the effects of N2O on GABAA, glutamate, AMPA and NMDA receptor-mediated currents (IGABA, IGlu, IAMPA and INMDA) elicited by exogenous application of GABA, glutamate, (S)-AMPA, and NMDA and spontaneous, miniature, and evoked GABAergic inhibitory and glutamatergic excitatory postsynaptic current (sIPSC, mIPSC, eIPSC, sEPSC, mEPSC and eEPSC) in mechanically dissociated CA3 neurons. eIPSC and eEPSC were evoked by focal electrical stimulation of a single bouton. Administration of 70% N2O altered neither IGABA nor the frequency and amplitude of both sIPSCs and mIPSCs. In contrast, N2O decreased the amplitude of eIPSCs, while increasing failure rates (Rf) and paired-pulse ratios (PPR) in a concentration-dependent manner. On the other hand, N2O decreased IGlu, IAMPA and INMDA. Again N2O did not change the frequency and amplitude of either sEPSCs of mEPSCs. N2O also decreased amplitudes of eEPSCs with increased Rf and PPR. The decay phases of all synaptic responses were unchanged. The present results indicated that N2O inhibits the activation of AMPA/KA and NMDA receptors and also that N2O preferentially depress the action potential-dependent GABA and glutamate releases but had little effects on spontaneous and miniature releases. PMID:26343381

  8. Epidermal laser stimulation of action potentials in the frog sciatic nerve

    NASA Astrophysics Data System (ADS)

    Jindra, Nichole M.; Goddard, Douglas; Imholte, Michelle; Thomas, Robert J.

    2010-01-01

    Measurements of laser-stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) are made using two infrared lasers. The dorsal sides of the frog's hind limbs are exposed to short-pulsed 1540- and 1064-nm wavelengths at three separate spot sizes: 2, 3, and 4 mm. Energy density thresholds are determined for eliciting an action potential at each experimental condition. Results from these exposures show similar evoked potential thresholds for both wavelengths. The 2-mm-diam spot sizes yield action potentials at radiant exposure levels almost double that seen with larger beam sizes.

  9. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

    NASA Astrophysics Data System (ADS)

    Crago, Patrick E.; Makowski, Nathaniel S.

    2014-10-01

    Objective. Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main results. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic

  10. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

    PubMed Central

    Crago, Patrick E; Makowski, Nathan S

    2014-01-01

    Objective Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main Results Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases.. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic

  11. Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

    PubMed

    Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

    2014-01-01

    Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed.

  12. Potential synergy of phytochemicals in cancer prevention: mechanism of action.

    PubMed

    Liu, Rui Hai

    2004-12-01

    Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer and cardiovascular disease. It is now widely believed that the actions of the antioxidant nutrients alone do not explain the observed health benefits of diets rich in fruits and vegetables, because taken alone, the individual antioxidants studied in clinical trials do not appear to have consistent preventive effects. Work performed by our group and others has shown that fruits and vegetable phytochemical extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. We proposed that the additive and synergistic effects of phytochemicals in fruits and vegetables are responsible for these potent antioxidant and anticancer activities and that the benefit of a diet rich in fruits and vegetables is attributed to the complex mixture of phytochemicals present in whole foods. This explains why no single antioxidant can replace the combination of natural phytochemicals in fruits and vegetables to achieve the health benefits. The evidence suggests that antioxidants or bioactive compounds are best acquired through whole-food consumption, not from expensive dietary supplements. We believe that a recommendation that consumers eat 5 to 10 servings of a wide variety of fruits and vegetables daily is an appropriate strategy for significantly reducing the risk of chronic diseases and to meet their nutrient requirements for optimum health.

  13. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    PubMed

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  14. RXP-E: A CX43-BINDING PEPTIDE THAT PREVENTS ACTION POTENTIAL PROPAGATION BLOCK

    PubMed Central

    Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi; Coombs, Wanda; Jalife, Jose; Nielsen, Morten S.; Taffet, Steven M.; Delmar, Mario

    2009-01-01

    Gap junctions (GJs) provide a low-resistance pathway for cardiac electrical propagation. The role of GJ regulation in arrhythmia is unclear, partly due to limited availability of pharmacological tools. Recently, we showed that a peptide called “RXP-E” binds to the carboxyl terminal of connexin43 (Cx43) and prevents chemically-induced uncoupling in Cx43-expressing N2a cells. Here, pull-down experiments show RXP-E binding to adult cardiac Cx43. Patch-clamp studies revealed that RXP-E prevented heptanol-induced and acidification-induced uncoupling in pairs of neonatal rat ventricular myocytes (NRVM’s). Separately, RXP-E was concatenated to a cytoplasmic transduction peptide for cytoplasmic translocation (CTP-RXP-E). The effect of RXP-E on action potential (AP) propagation was assessed by high resolution optical mapping in monolayers of NRVM’s, containing ~20% of randomly distributed myofibroblasts. In contrast to control experiments, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, AP propagation was maintained, albeit at a slower velocity. Similarly, intracellular acidification (pHi=6.2) caused a loss of AP propagation in control monolayers; however, propagation was maintained in CTP-RXP-E treated cells, though at a slower rate. Patch clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or amplitude of Kir2.1/Kir2.3 currents. RXP-E is the first synthetic molecule known to: (1) bind cardiac Cx43; (2) prevent heptanol and acidification-induced uncoupling of cardiac GJ’s and 3) preserve AP propagation among cardiac myocytes. RXP-E can be used to characterize the role of GJs in the function of multicellular systems, including the heart. PMID:18669919

  15. Disruption of action potential and calcium signaling properties in malformed myofibers from dystrophin-deficient mice

    PubMed Central

    Hernández-Ochoa, Erick O; Pratt, Stephen J P; Garcia-Pelagio, Karla P; Schneider, Martin F; Lovering, Richard M

    2015-01-01

    Duchenne muscular dystrophy (DMD), the most common and severe muscular dystrophy, is caused by the absence of dystrophin. Muscle weakness and fragility (i.e., increased susceptibility to damage) are presumably due to structural instability of the myofiber cytoskeleton, but recent studies suggest that the increased presence of malformed/branched myofibers in dystrophic muscle may also play a role. We have previously studied myofiber morphology in healthy wild-type (WT) and dystrophic (MDX) skeletal muscle. Here, we examined myofiber excitability using high-speed confocal microscopy and the voltage-sensitive indicator di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate (di-8-ANEPPS) to assess the action potential (AP) properties. We also examined AP-induced Ca2+ transients using high-speed confocal microscopy with rhod-2, and assessed sarcolemma fragility using elastimetry. AP recordings showed an increased width and time to peak in malformed MDX myofibers compared to normal myofibers from both WT and MDX, but no significant change in AP amplitude. Malformed MDX myofibers also exhibited reduced AP-induced Ca2+ transients, with a further Ca2+ transient reduction in the branches of malformed MDX myofibers. Mechanical studies indicated an increased sarcolemma deformability and instability in malformed MDX myofibers. The data suggest that malformed myofibers are functionally different from myofibers with normal morphology. The differences seen in AP properties and Ca2+ signals suggest changes in excitability and remodeling of the global Ca2+ signal, both of which could underlie reported weakness in dystrophic muscle. The biomechanical changes in the sarcolemma support the notion that malformed myofibers are more susceptible to damage. The high prevalence of malformed myofibers in dystrophic muscle may contribute to the progressive strength loss and fragility seen in dystrophic muscles. PMID:25907787

  16. Developmental changes in the inward current of the action potential of Rohon-Beard neurones

    PubMed Central

    Baccaglini, Paola I.; Spitzer, Nicholas C.

    1977-01-01

    1. Rohon-Beard cells in the spinal cord of Xenopus tadpoles have been studied in animals from early neural tube to free-swimming larval stages. The onset and further development of electrical excitability of these neurones has been investigated in different ionic environments, to determine the ionic species carrying the inward current of the action potential. 2. The cells appear inexcitable at early stages (Nieuwkoop & Faber stages 18-20) and do not give action potentials to depolarizing current pulses. 3. The action potential is first recorded at stage 20. (A) The inward current is carried by Ca2+ at stages 20-25, since it is blocked by mm quantitites of La3+, Co2+ or Mn2+ and is unaffected by removal of Na+ or the addition of tetrodotoxin (TTX). (B) The action potential is an elevated plateau of long duration (mean 190 msec at stages 20-22). The duration decreases exponentially with repetitive stimulation. (C) The specific Ca2+ conductance (gCa) at the onset of the plateau of the action potential is 2·6 × 10-4 mho/cm2. Calculations show that a single action potential raises [Ca2+]1 by more than 100-fold. 4. At later times (stages 25-40), the inward current of the action potential is carried by both Na+ and Ca2+: the action potential has two components, an initial spike which is blocked by removal of Na+ or addition of TTX, followed by a plateau which is blocked by La3+, Co2+ or Mn2+. 5. Finally (stages 40-51), the inward current is primarily carried by Na+, since the action potential is blocked only by removal of Na+ or addition of TTX, and the overshoot agrees with the prediction of the Nernst equation for a Na-selective membrane. When the outward current channel is blocked and cells exposed to Na-free solutions, 67% of cells at the latest stages studied were incapable of producing action potentials in which the inward current is carried by divalent cations. 6. The duration of the action potential decreases from a maximum of about 1000 msec to about 1 msec

  17. Inhibition of the compound action potentials of frog sciatic nerves by aroma oil compounds having various chemical structures

    PubMed Central

    Ohtsubo, Sena; Fujita, Tsugumi; Matsushita, Akitomo; Kumamoto, Eiichi

    2015-01-01

    Plant-derived chemicals including aroma oil compounds have an ability to inhibit nerve conduction and modulate transient receptor potential (TRP) channels. Although applying aroma oils to the skin produces a local anesthetic effect, this has not been yet examined throughly. The aim of the present study was to know how nerve conduction inhibitions by aroma oil compounds are related to their chemical structures and whether these activities are mediated by TRP activation. Compound action potentials (CAPs) were recorded from the frog sciatic nerve by using the air-gap method. Citral (aldehyde), which activates various types of TRP channels, attenuated the peak amplitude of CAP with the half-maximal inhibitory concentration (IC50) value of 0.46 mmol/L. Another aldehyde (citronellal), alcohol (citronellol, geraniol, (±)-linalool, (−)-linalool, (+)-borneol, (−)-borneol, α-terpineol), ester (geranyl acetate, linalyl acetate, bornyl acetate), and oxide (rose oxide) compounds also reduced CAP peak amplitudes (IC50: 0.50, 0.35, 0.53, 1.7, 2.0, 1.5, 2.3, 2.7, 0.51, 0.71, 0.44, and 2.6 mmol/L, respectively). On the other hand, the amplitudes were reduced by a small extent by hydrocarbons (myrcene and p-cymene) and ketone (camphor) at high concentrations (2–5 mmol/L). The activities of citral and other TRP agonists ((+)-borneol and camphor) were resistant to TRP antagonist ruthenium red. An efficacy sequence for the CAP inhibitions was generally aldehydes ≥ esters ≥ alcohols > oxides >> hydrocarbons. The CAP inhibition by the aroma oil compound was not related to its octanol–water partition coefficient. It is suggested that aroma oil compounds inhibit nerve conduction in a manner specific to their chemical structures without TRP activation. PMID:26038703

  18. [Dose-dependent tazepam modulation of amplitude-temporal characteristics of thalamocortical responses and the constant potential of the sensorimotor cortex in rabbits at eye opening].

    PubMed

    Shimko, I A; Fokin, V F

    2000-01-01

    The pronounced benzodiazepine (antiphobic) modulation of the amplitude-temporal parameters of different components of the thalamocortical responses (TCR) of the sensorimotor cortex is observed in rabbits in their early postnatal ontogeny. This modulation is of a dose-dependent character and is registered not after the injection of tazepam in a concentration of the "therapeutic tranquilizing window" but also in the psychotoxic plasma range. A gradual increase in blood tazepam concentration in a young rabbit pup is accompanied by the wave-like and differential decrease in the amplitude of the second and third positive (P2 and P3) and third negative (N3) TCR components, while the second negative (N2) and fourth positive (P4) components tend to a wave-like increase. The dose-dependent dynamics of tazepam modulation of the P2, P3, and N3 latencies is characterized by a wave-like and differential increase. The latency of P4 decreases slightly and that of the N2 increases with a low degree of significance. The selective dynamics of benzodiazepine modulation appears to be related with peculiarities of the electrogenesis of each of the components. The dose-dependent modulation of the level of cortical DC potential is of the same character as the respective amplitude changes in P2, P3, and N3, but its fluctiatuons are more pronounced.

  19. Is action potential duration of the intact dog heart related to contractility or stimulus rate?

    PubMed

    Drake, A J; Noble, M I; Schouten, V; Seed, A; Ter Keurs, H E; Wohlfart, B

    1982-10-01

    1. The contractility (maximum rate of rise of left ventricular pressure) and action potential duration were measured in intact closed-chest anaesthetized dogs with complete atrioventricular dissociation and beta-adrenergic blockade.2. Measurements were confined to test beats following a 1 sec interval. Prior to the test interval (priming period) a variety of potentiating stimulus trains were introduced.3. When the frequency of stimulation was increased in the priming period (frequency potentiation), there was an inverse relationship between action potential duration and contractility of the test beat.4. When the test beat was potentiated by a single beat terminating the priming period with one short interval (post-extrasystolic potentiation), there was no relationship between the action potential duration and contractility of the test beat.5. Paired pulse stimulation was used for any given frequency to vary contractility by short interval potentiation. For any given frequency of stimulation there was no relationship between action potential duration and contractility of the test beat. For any given value of contractility, action potential duration decreased with increased frequency of stimulation.6. The introduction of a high frequency train caused a step decrease in action potential duration on the first beat of the train. This was followed by a further slow decline in action potential duration with a time course of over 3 min. These two changes could be dissociated by the introduction during the train of one second interval test pulses, which only showed the slow shortening.7. The lack of a consistent relationship between action potential duration and contractility of the test beat disagrees with the hypothesis that repolarization is controlled by the activator calcium responsible for the contractility. The action potential shortening associated with increased frequency is related to the frequency change per se.8. The slow time course of change in action

  20. Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

    PubMed Central

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation. PMID:24465197

  1. Consequences of converting graded to action potentials upon neural information coding and energy efficiency.

    PubMed

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na(+) and K(+) channels, with generator potential and graded potential models lacking voltage-gated Na(+) channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na(+) channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a 'footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation.

  2. Spontaneous miniature hyperpolarizations affect threshold for action potential generation in mudpuppy cardiac neurons.

    PubMed

    Parsons, Rodney L; Barstow, Karen L; Scornik, Fabiana S

    2002-09-01

    Mudpuppy parasympathetic neurons exhibit spontaneous miniature hyperpolarizations (SMHs) that are generated by potassium currents, which are spontaneous miniature outward currents (SMOCs), flowing through clusters of large conductance voltage- and calcium (Ca(2+))-activated potassium (BK) channels. The underlying SMOCs are initiated by a Ca(2+)-induced Ca(2+) release (CICR) mechanism. Perforated-patch whole cell voltage recordings were used to determine whether activation of SMHs contributed to action potential (AP) repolarization or affected the latency to AP generation. Blockade of BK channels by iberiotoxin (IBX, 100 nM) slowed AP repolarization and increased AP duration. Treatment with omega-conotoxin GVIA (3 microM) or nifedipine (10 microM) to inhibit Ca(2+) influx through N- or L-type voltage-dependent calcium channels (VDCCs), respectively, also decreased the rate of AP repolarization and increased AP duration. Elimination of CICR by treatment with either thapsigargin (1 microM) or ryanodine (10 microM) produced no significant change in AP repolarization or duration. Blockade of BK channels with IBX and inhibition of N-type VDCCs with omega-conotoxin GVIA, but not inhibition of L-type VDCCs with nifedipine, decreased the latency of AP generation. A decrease in latency to AP generation occurred with elimination of SMHs by inhibition of CICR following treatment with thapsigargin. Ryanodine treatment decreased AP latency in three of six cells. Apamin (100 nM) had no affect on AP repolarization, duration, or latency to AP generation, but did decrease the hyperpolarizing afterpotential (HAP). Inhibition of L-type VDCCs by nifedipine also decreased HAP amplitude. Inhibition of CICR by either thapsigargin or ryanodine treatment increased the number of APs generated with long depolarizing current pulses, whereas exposure to IBX or omega-conotoxin GVIA depressed excitability. We conclude that CICR, the process responsible for SMH generation, represents a unique

  3. Action Potential-Independent and Nicotinic Receptor-Mediated Concerted Release of Multiple Quanta at Hippocampal CA3–Mossy Fiber Synapses

    PubMed Central

    Sharma, Geeta; Grybko, Michael; Vijayaraghavan, Sukumar

    2009-01-01

    Presynaptic action potential-independent transmitter release is a potential means of information transfer across synapses. We show that in the hippocampal mossy fiber boutons, activation of the α7-subtype of nicotinic acetylcholine receptors (α7-nAChRs) results in a large increase in the amplitude of spontaneous events, resulting from concerted release of multiple quanta from the mossy fiber boutons. This amplitude increase is abolished at low temperatures. Activation of α7-nAChRs causes a rise in intraterminal calcium at mossy fiber boutons, involving ryanodine receptors. Regulation of concerted release requires the subsequent activation of presynaptic calcium/calmodulin-dependent protein kinase II (CaMKII). Activation of CaMKII is required to drive presynaptic action potential-independent transmission at the mossy fiber–CA3 pyramidal cell synapse. The effects of α7-nAChR activation are mediated by biologically relevant doses of nicotine. Our results demonstrate a novel form of synaptic plasticity mediated by presynaptic α7-nAChRs and store calcium that is temporally different and might respond to a different history of synaptic activity than that mediated by incoming action potentials. PMID:18322100

  4. Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential

    PubMed Central

    1990-01-01

    The properties of the autonomically regulated chloride current (ICl) were studied in isolated guinea pig ventricular myocytes. This current was elicited upon exposure to isoproterenol (ISO) and reversed upon concurrent exposure to acetylcholine (ACh). ICl was time independent and exhibited outward rectification. The responses to ISO and ACh could be blocked by propranolol and atropine, respectively, and ICl was also elicited by forskolin, 8-bromoadenosine 3',5'-cyclic monophosphate, and 3-isobutyl-l-methylxanthine, indicating that the current is regulated through a cAMP-dependent pathway. The reversal potential of the ISO- induced current followed the predicted chloride equilibrium potential, consistent with it being carried predominantly by Cl-. Activation of ICl produced changes in the resting membrane potential and action potential duration, which were Cl- gradient dependent. These results indicate that under physiological conditions ICl may play an important role in regulating action potential duration and resting membrane potential in mammalian cardiac myocytes. PMID:2165130

  5. Detection and classification of raw action potential patterns in human Muscle Sympathetic Nerve Activity.

    PubMed

    Salmanpour, Aryan; Brown, Lyndon J; Shoemaker, J K

    2008-01-01

    The Muscle Sympathetic Nerve Activity (MSNA) consists of synchronous neural discharges separated by periods of neural silence dominated by heavy background noise. During measurement with electrodes, the raw MSNA signal is amplified, band-pass filtered, rectified and integrated. This integration process removes much neurophysiological information. In this paper a method for detecting a raw action potential (before the pre-amplifier) and filtered action potential (after the band-pass filter) is presented. This method is based on stationary wavelet transform (SWT) and a peak detection algorithm. Also, the detected action potentials were clustered using the k-means method and the cluster averages were calculated. The action potential detector and classification algorithm are evaluated using real MSNA recorded from three healthy subjects.

  6. All optical experimental design for neuron excitation, inhibition, and action potential detection

    NASA Astrophysics Data System (ADS)

    Walsh, Alex J.; Tolstykh, Gleb; Martens, Stacey; Sedelnikova, Anna; Ibey, Bennett L.; Beier, Hope T.

    2016-03-01

    Recently, infrared light has been shown to both stimulate and inhibit excitatory cells. However, studies of infrared light for excitatory cell inhibition have been constrained by the use of invasive and cumbersome electrodes for cell excitation and action potential recording. Here, we present an all optical experimental design for neuronal excitation, inhibition, and action potential detection. Primary rat neurons were transfected with plasmids containing the light sensitive ion channel CheRiff. CheRiff has a peak excitation around 450 nm, allowing excitation of transfected neurons with pulsed blue light. Additionally, primary neurons were transfected with QuasAr2, a fast and sensitive fluorescent voltage indicator. QuasAr2 is excited with yellow or red light and therefore does not spectrally overlap CheRiff, enabling imaging and action potential activation, simultaneously. Using an optic fiber, neurons were exposed to blue light sequentially to generate controlled action potentials. A second optic fiber delivered a single pulse of 1869nm light to the neuron causing inhibition of the evoked action potentials (by the blue light). When used in concert, these optical techniques enable electrode free neuron excitation, inhibition, and action potential recording, allowing research into neuronal behaviors with high spatial fidelity.

  7. Distinct electrophysiological potentials for intention in action and prior intention for action.

    PubMed

    Vinding, Mikkel C; Jensen, Mads; Overgaard, Morten

    2014-01-01

    The role of conscious intention in relation to motoric movements has become a major topic of investigation in neuroscience. Traditionally, reports of conscious intention have been compared to various features of the readiness-potential (RP)--an electrophysiological signal that appears before voluntary movements. Experiments, however, tend to study intentions in immediate relation to movements (proximal intentions), thus ignoring other aspects of intentions such as planning or deciding in advance of movement (distal intentions). The current study examines the difference in electrophysiological activity between proximal intention and distal intention, using electroencephalography (EEG). Participants had to form an intention to move and then wait 2.5 sec before performing the actual movement. In this way, the electrophysiological activity related to forming a conscious intention was separated from any confounding activity related to automated motor activity. This was compared to conditions in which participants had to act as soon as they had the intention and a condition where participants acted upon an external cue 2.5 sec prior to movement. We examined the RP for the three conditions. No difference was found in early RP, but late RP differed significantly depending on the type of intention. In addition, we analysed signals during a longer time-interval starting before the time of distal intention formation until after the actual movement concluded. Results showed a slow negative electrophysiological "intention potential" above the mid-frontal areas at the time participants formed a distal intention. This potential was only found when the distal intention was self-paced and not when the intention was formed in response to an external cue.

  8. Generation of slow-wave-type action potentials in canine colon smooth muscle involves a non-L-type Ca2+ conductance.

    PubMed Central

    Huizinga, J D; Farraway, L; Den Hertog, A

    1991-01-01

    1. The hypothesis was addressed that a non-L-type calcium conductance is involved in the generation of the initial part of the slow-wave-type action potential in the canine colon. 2. In the absence of a sodium and chloride gradient (NaCl replaced by glucamine), and in the presence of nitrendipine (in 'glucamine-nitrendipine' Krebs solution), a major portion of the upstroke potential of the slow wave persists at unchanged frequency. 3. In 'glucamine-nitrendipine' Krebs solution, the rate of rise and amplitude of the upstroke potential is reduced by removal of extracellular calcium in a concentration-dependent manner. 4. The rate of rise and the amplitude of the upstroke potential is in a concentration-dependent manner reduced by Ni2+ greater than Cd2+ greater than Co2+ greater than Mg2+. 5. In 'glucamine-nitrendipine' Krebs solution, Ba2+ cannot replace Ca2+ in the generation of the upstroke potential. 6. Positive evidence was obtained for the hypothesis that a non-L-type calcium conductance is involved in the initiation of the slow-wave-type action potential in colonic smooth muscle. PMID:1724671

  9. Assessing the Electrode-Neuron Interface with the Electrically Evoked Compound Action Potential, Electrode Position, and Behavioral Thresholds.

    PubMed

    DeVries, Lindsay; Scheperle, Rachel; Bierer, Julie Arenberg

    2016-06-01

    Variability in speech perception scores among cochlear implant listeners may largely reflect the variable efficacy of implant electrodes to convey stimulus information to the auditory nerve. In the present study, three metrics were applied to assess the quality of the electrode-neuron interface of individual cochlear implant channels: the electrically evoked compound action potential (ECAP), the estimation of electrode position using computerized tomography (CT), and behavioral thresholds using focused stimulation. The primary motivation of this approach is to evaluate the ECAP as a site-specific measure of the electrode-neuron interface in the context of two peripheral factors that likely contribute to degraded perception: large electrode-to-modiolus distance and reduced neural density. Ten unilaterally implanted adults with Advanced Bionics HiRes90k devices participated. ECAPs were elicited with monopolar stimulation within a forward-masking paradigm to construct channel interaction functions (CIF), behavioral thresholds were obtained with quadrupolar (sQP) stimulation, and data from imaging provided estimates of electrode-to-modiolus distance and scalar location (scala tympani (ST), intermediate, or scala vestibuli (SV)) for each electrode. The width of the ECAP CIF was positively correlated with electrode-to-modiolus distance; both of these measures were also influenced by scalar position. The ECAP peak amplitude was negatively correlated with behavioral thresholds. Moreover, subjects with low behavioral thresholds and large ECAP amplitudes, averaged across electrodes, tended to have higher speech perception scores. These results suggest a potential clinical role for the ECAP in the objective assessment of individual cochlear implant channels, with the potential to improve speech perception outcomes. PMID:26926152

  10. Modulatory action of acetylcholine on the Na+-dependent action potentials in Kenyon cells isolated from the mushroom body of the cricket brain.

    PubMed

    Terazima, E; Yoshino, M

    2010-12-01

    Kenyon cells, intrinsic neurons of the insect mushroom body, have been assumed to be a site of conditioning stimulus (CS) and unconditioned stimulus (US) association in olfactory learning and memory. Acetylcholine (ACh) has been implicated to be a neurotransmitter mediating CS reception in Kenyon cells, causing rapid membrane depolarization via nicotinic ACh receptors. However, the long-term effects of ACh on the membrane excitability of Kenyon cells are not fully understood. In this study, we examined the effects of ACh on Na(+) dependent action potentials (Na(+) spikes) elicited by depolarizing current injection and on net membrane currents under the voltage clamp condition in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Current-clamp studies using amphotericin B perforated-patch recordings showed that freshly dispersed cricket Kenyon cells could produce repetitive Na(+) spikes in response to prolonged depolarizing current injection. Bath application of ACh increased both the instantaneous frequency and the amplitudes of Na(+) spikes. This excitatory action of ACh on Kenyon cells is attenuated by the pre-treatment of the cells with the muscarinic receptor antagonists, atropine and scopolamine, but not by the nicotinic receptor antagonist mecamylamine. Voltage-clamp studies further showed that bath application of ACh caused an increase in net inward currents that are sensitive to TTX, whereas outward currents were decreased by this treatment. These results indicate that in order to mediate CS, ACh may modulate the firing properties of Na(+) spikes of Kenyon cells through muscarinic receptor activation, thus increasing Na conductance and decreasing K conductance.

  11. 16-Channel Organic Electrochemical Transistor Array for In Vitro Conduction Mapping of Cardiac Action Potential.

    PubMed

    Gu, Xi; Yao, Chunlei; Liu, Ying; Hsing, I-Ming

    2016-09-01

    16-Channel organic electrochemical transistor arrays (OECTs) are developed for mapping the propagation and studying the characteristics of action potentials of primary cardiomyocytes. The physiological activities of a rat cardiomyocyte monolayer during a long-term culturing is revealed by this biocompatible, low-cost, and high transconductance organic electronic device. OECT has great potential to be used in cardiac and neuronal drug screening.

  12. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 13 2012-01-01 2012-01-01 false Reporting potential natural disasters and initial... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) EMERGENCY Disaster Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose....

  13. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 13 2011-01-01 2009-01-01 true Reporting potential natural disasters and initial... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) EMERGENCY Disaster Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose....

  14. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) EMERGENCY Disaster Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose....

  15. Sodium and calcium currents shape action potentials in immature mouse inner hair cells.

    PubMed

    Marcotti, Walter; Johnson, Stuart L; Rusch, Alfons; Kros, Corne J

    2003-11-01

    Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both alpha1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at -71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency.

  16. Sodium and calcium currents shape action potentials in immature mouse inner hair cells

    PubMed Central

    Marcotti, Walter; Johnson, Stuart L; Rüsch, Alfons; Kros, Corné J

    2003-01-01

    Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both α1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at −71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency. PMID:12937295

  17. Action!

    ERIC Educational Resources Information Center

    Senese, Joseph

    1998-01-01

    A small group of teachers at one Illinois high school is helping to effect and promote change. Through the Action Research Laboratory (ARL), teams of teachers conduct collaborative action research to improve classroom practices. Data from the first two years of the ARL indicate that teachers are eager to participate in, and have thrived in, their…

  18. 9-Anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential.

    PubMed

    Váczi, Krisztina; Hegyi, Bence; Ruzsnavszky, Ferenc; Kistamás, Kornél; Horváth, Balázs; Bányász, Tamás; Nánási, Péter P; Szentandrássy, Norbert; Magyar, János

    2015-01-01

    Understanding the role of ionic currents in shaping the cardiac action potential (AP) has great importance as channel malfunctions can lead to sudden cardiac death by inducing arrhythmias. Therefore, researchers frequently use inhibitors to selectively block a certain ion channel like 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC) for calcium-activated chloride current (ICl(Ca)). This study aims to explore which blocker is preferable to study ICl(Ca). Whole-cell voltage-clamp technique was used to record ICa,L, IKs, IKr and IK1, while action potentials were measured using sharp microelectrodes. DIDS- (0.2 mM) and 9-AC-sensitive (0.5 mM) currents were identical in voltage-clamp conditions, regardless of intracellular Ca(2+) buffering. DIDS-sensitive current amplitude was larger with the increase of stimulation rate and correlated well with the rate-induced increase of calcium transients. Both drugs increased action potential duration (APD) to the same extent, but the elevation of the plateau potential was more pronounced with 9-AC at fast stimulation rates. On the contrary, 9-AC did not influence either the AP amplitude or the maximal rate of depolarization (V max), but DIDS caused marked reduction of V max. Both inhibitors reduced the magnitude of phase-1, but, at slow stimulation rates, this effect of DIDS was larger. All of these actions on APs were reversible upon washout of the drugs. Increasing concentrations of 9-AC between 0.1 and 0.5 mM in a cumulative manner gradually reduced phase-1 and increased APD. 9-AC at 1 mM had no additional actions upon perfusion after 0.5 mM. The half-effective concentration of 9-AC was approximately 160 μM with a Hill coefficient of 2. The amplitudes of ICa,L, IKs, IKr and IK1 were not changed by 0.5 mM 9-AC. These results suggest that DIDS is equally useful to study ICl(Ca) during voltage-clamp but 9-AC is superior in AP measurements for studying the physiological role of

  19. Initiation and blocking of the action potential in an axon in weak ultrasonic or microwave fields.

    PubMed

    Shneider, M N; Pekker, M

    2014-05-01

    In this paper, we analyze the effect of the redistribution of the transmembrane ion channels in an axon caused by longitudinal acoustic vibrations of the membrane. These oscillations can be excited by an external source of ultrasound and weak microwave radiation interacting with the charges sitting on the surface of the lipid membrane. It is shown, using the Hodgkin-Huxley model of the axon, that the density redistribution of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At the significant redistribution of sodium channels in the membrane, the rarefaction zones of the transmembrane channel density are formed, blocking the propagation of the action potential. Blocking the action potential propagation along the axon is shown to cause anesthesia in the example case of a squid axon. Various approaches to experimental observation of the effects considered in this paper are discussed. PMID:25353835

  20. Initiation and blocking of the action potential in an axon in weak ultrasonic or microwave fields

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2014-05-01

    In this paper, we analyze the effect of the redistribution of the transmembrane ion channels in an axon caused by longitudinal acoustic vibrations of the membrane. These oscillations can be excited by an external source of ultrasound and weak microwave radiation interacting with the charges sitting on the surface of the lipid membrane. It is shown, using the Hodgkin-Huxley model of the axon, that the density redistribution of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At the significant redistribution of sodium channels in the membrane, the rarefaction zones of the transmembrane channel density are formed, blocking the propagation of the action potential. Blocking the action potential propagation along the axon is shown to cause anesthesia in the example case of a squid axon. Various approaches to experimental observation of the effects considered in this paper are discussed.

  1. Optical magnetic detection of single-neuron action potentials using NV-diamond

    NASA Astrophysics Data System (ADS)

    Turner, Matthew; Barry, John; Schloss, Jennifer; Glenn, David; Walsworth, Ron

    2016-05-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential dynamics in whole organisms with single-neuron resolution. Here, we report a new approach to this problem: using nitrogen-vacancy (NV) color centers in diamond to measure the time-dependent magnetic fields produced by single-neuron action potentials. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional mammalian neuronal networks.

  2. Memantine reduces repetitive action potential firing in spinal cord nerve cell cultures.

    PubMed

    Netzer, R; Bigalke, H

    1990-09-21

    (1) The anticonvulsant effects of memantine were examined and compared with those of baclofen in monolayer primary cultures of murine nerve cells using conventional intracellular recordings. (2) Memantine and baclofen (each 10-100 microM) decreased spontaneous synaptic activity when action potential frequencies exceeded 6 Hz. Neurons firing action potentials at frequencies below 6 Hz (about 90% of all impaled cells), however, were not affected by the drugs. (3) Memantine reduced the duration of strychnine-elicited bursts and the firing rate of action potentials within a burst. In contrast, baclofen lowered the frequency of the bursts without reducing intra-burst firing. The duration of the bursts was increased. (4) Memantine, but not baclofen, reduced the extent of sustained repetitive firing evoked by pulses of depolarizing current. (5) In the presence of memantine, the second of two electrically evoked action potentials increasingly failed to appear as the intervals between successive stimulating pulses were shortened. Such an effect was not seen when baclofen was applied. Thus, both antispastic agents, memantine and baclofen, reduce hyperactivity of spinal cord neurons in culture, although their mechanisms of action are different.

  3. Potentiation of the cytotoxic action of melphalan and "activated" cyclophosphamide against cultured tumor cells by centrophenoxine.

    PubMed

    Sladek, N E

    1977-01-01

    Centrophenoxine, without antitumor activity itself, enhanced the cytotoxic action of melphalan and "activated" cyclophosphamide against mouse P388 lymphoma and rat W256 carcinosarcoma cells growing in static suspension culture. The concentration of alkylating agent required for 99% cell-kill was approximately halved when centrophenoxine was also present during exposure to the antitumor drug. Maximum potentiation by centrophenoxine of the cytotoxic action of melphalan occurred when cells were exposed to the two agents simultaneously; little or no potentiation was observed when cells were exposed to centrophenoxine before or after exposure to the alkylating agent.

  4. Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea.

    PubMed

    Sendin, Gaston; Bourien, Jérôme; Rassendren, François; Puel, Jean-Luc; Nouvian, Régis

    2014-02-01

    Inner hair cells (IHCs) are the primary transducer for sound encoding in the cochlea. In contrast to the graded receptor potential of adult IHCs, immature hair cells fire spontaneous calcium action potentials during the first postnatal week. This spiking activity has been proposed to shape the tonotopic map along the ascending auditory pathway. Using perforated patch-clamp recordings, we show that developing IHCs fire spontaneous bursts of action potentials and that this pattern is indistinguishable along the basoapical gradient of the developing cochlea. In both apical and basal IHCs, the spiking behavior undergoes developmental changes, where the bursts of action potential tend to occur at a regular time interval and have a similar length toward the end of the first postnatal week. Although disruption of purinergic signaling does not interfere with the action potential firing pattern, pharmacological ablation of the α9α10 nicotinic receptor elicits an increase in the discharge rate. We therefore suggest that in addition to carrying place information to the ascending auditory nuclei, the IHCs firing pattern controlled by the α9α10 receptor conveys a temporal signature of the cochlear development. PMID:24429348

  5. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance

    PubMed Central

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

    2016-01-01

    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents. PMID:27525414

  6. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

    PubMed

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

    2016-01-01

    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents. PMID:27525414

  7. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    PubMed

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected.

  8. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    PubMed

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected. PMID:26686984

  9. Viewing Objects and Planning Actions: On the Potentiation of Grasping Behaviours by Visual Objects

    ERIC Educational Resources Information Center

    Makris, Stergios; Hadar, Aviad A.; Yarrow, Kielan

    2011-01-01

    How do humans interact with tools? Gibson (1979) suggested that humans perceive directly what tools afford in terms of meaningful actions. This "affordances" hypothesis implies that visual objects can potentiate motor responses even in the absence of an intention to act. Here we explore the temporal evolution of motor plans afforded by common…

  10. 76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-19

    ... Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and... extension and associated actions for Devils Lake Regional Airport in Devils Lake, North Dakota. SUMMARY: The FAA has issued the final EA and FONSI/ROD for the proposed Runway 13 extension and associated...

  11. Youth Participatory Action Research and Educational Transformation: The Potential of Intertextuality as a Methodological Tool

    ERIC Educational Resources Information Center

    Bertrand, Melanie

    2016-01-01

    In this article, Melanie Bertrand explores the potential of using the concept of intertextuality--which captures the way snippets of written or spoken text from one source become incorporated into other sources--in the study and practice of youth participatory action research (YPAR). Though this collective and youth-centered form of research…

  12. Primary cortical representation of sounds by the coordination of action-potential timing

    NASA Astrophysics Data System (ADS)

    Decharms, R. Christopher; Merzenich, Michael M.

    1996-06-01

    CORTICAL population coding could in principle rely on either the mean rate of neuronal action potentials, or the relative timing of action potentials, or both. When a single sensory stimulus drives many neurons to fire at elevated rates, the spikes of these neurons become tightly synchronized1,2, which could be involved in 'binding' together individual firing-rate feature representations into a unified object percept3. Here we demonstrate that the relative timing of cortical action potentials can signal stimulus features themselves, a function even more basic than feature grouping. Populations of neurons in the primary auditory cortex can coordinate the relative timing of their action potentials such that spikes occur closer together in time during continuous stimuli. In this way cortical neurons can signal stimuli even when their firing rates do not change. Population coding based on relative spike timing can systematically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.

  13. Action potential energetics at the organismal level reveal a trade-off in efficiency at high firing rates.

    PubMed

    Lewis, John E; Gilmour, Kathleen M; Moorhead, Mayron J; Perry, Steve F; Markham, Michael R

    2014-01-01

    The energetic costs of action potential (AP) production constrain the evolution of neural codes and brain networks. Cellular-level estimates of AP-related costs are typically based on voltage-dependent Na(+) currents that drive active transport by the Na(+)/K(+) ATPase to maintain the Na(+) and K(+) ion concentration gradients necessary for AP production. However, these estimates of AP cost have not been verified at the organismal level. Electric signaling in the weakly electric fish Eigenmannia virescens requires that specialized cells in an electric organ generate APs with large Na(+) currents at high rates (200-600 Hz). We measured these currents using a voltage-clamp protocol and then estimated the energetic cost at the cellular level using standard methods. We then used this energy-intensive signaling behavior to measure changes in whole-animal energetics for small changes in electric discharge rate. At low rates, the whole-animal measure of AP cost was similar to our cellular-level estimates. However, AP cost increased nonlinearly with increasing firing rates. We show, with a biophysical model, that this nonlinearity can arise from the increasing cost of maintaining AP amplitude at high rates. Our results confirm that estimates of energetic costs based on Na(+) influx are appropriate for low baseline firing rates, but that extrapolating to high firing rates may underestimate true costs in cases in which AP amplitude does not decrease. Moreover, the trade-off between energetic cost and firing rate suggests an additional constraint on the evolution of high-frequency signaling in neuronal systems. PMID:24381281

  14. Pre & Postsynaptic Tuning of Action Potential Timing by Spontaneous GABAergic Activity

    PubMed Central

    Caillard, Olivier

    2011-01-01

    Frequency and timing of action potential discharge are key elements for coding and transfer of information between neurons. The nature and location of the synaptic contacts, the biophysical parameters of the receptor-operated channels and their kinetics of activation are major determinants of the firing behaviour of each individual neuron. Ultimately the intrinsic excitability of each neuron determines the input-output function. Here we evaluate the influence of spontaneous GABAergic synaptic activity on the timing of action potentials in Layer 2/3 pyramidal neurones in acute brain slices from the somatosensory cortex of young rats. Somatic dynamic current injection to mimic synaptic input events was employed, together with a simple computational model that reproduce subthreshold membrane properties. Besides the well-documented control of neuronal excitability, spontaneous background GABAergic activity has a major detrimental effect on spike timing. In fact, GABAA receptors tune the relationship between the excitability and fidelity of pyramidal neurons via a postsynaptic (the reversal potential for GABAA activity) and a presynaptic (the frequency of spontaneous activity) mechanism. GABAergic activity can decrease or increase the excitability of pyramidal neurones, depending on the difference between the reversal potential for GABAA receptors and the threshold for action potential. In contrast, spike time jitter can only be increased proportionally to the difference between these two membrane potentials. Changes in excitability by background GABAergic activity can therefore only be associated with deterioration of the reliability of spike timing. PMID:21789249

  15. Syzygies probing scattering amplitudes

    NASA Astrophysics Data System (ADS)

    Chen, Gang; Liu, Junyu; Xie, Ruofei; Zhang, Hao; Zhou, Yehao

    2016-09-01

    We propose a new efficient algorithm to obtain the locally minimal generating set of the syzygies for an ideal, i.e. a generating set whose proper subsets cannot be generating sets. Syzygy is a concept widely used in the current study of scattering amplitudes. This new algorithm can deal with more syzygies effectively because a new generation of syzygies is obtained in each step and the irreducibility of this generation is also verified in the process. This efficient algorithm can also be applied in getting the syzygies for the modules. We also show a typical example to illustrate the potential application of this method in scattering amplitudes, especially the Integral-By-Part(IBP) relations of the characteristic two-loop diagrams in the Yang-Mills theory.

  16. 'Catching the waves' - slow cortical potentials as moderator of voluntary action.

    PubMed

    Schmidt, Stefan; Jo, Han-Gue; Wittmann, Marc; Hinterberger, Thilo

    2016-09-01

    The readiness potential is an ongoing negativity in the EEG preceding a self-initiated movement by approximately 1.5s. So far it has predominantly been interpreted as a preparatory signal with a causal link to the upcoming movement. Here a different hypothesis is suggested which we call the selective slow cortical potential sampling hypothesis. In this review of recent research results we argue that the initiation of a voluntary action is more likely during negative fluctuations of the slow cortical potential and that the sampling and averaging of many trials leads to the observed negativity. That is, empirical evidence indicates that the early readiness potential is not a neural correlate of preconscious motor preparation and thus a determinant of action. Our hypothesis thereafter challenges the classic interpretation of the Libet experiment which is often taken as proof that there is no free will. We furthermore suggest that slow cortical potentials are related to an urge to act but are not a neural indicator of the decision process of action initiation. PMID:27328786

  17. The DBI action, higher-derivative supergravity, and flattening inflaton potentials

    NASA Astrophysics Data System (ADS)

    Bielleman, Sjoerd; Ibáñez, Luis E.; Pedro, Francisco G.; Valenzuela, Irene; Wieck, Clemens

    2016-05-01

    In string theory compactifications it is common to find an effective Lagrangian for the scalar fields with a non-canonical kinetic term. We study the effective action of the scalar position moduli of Type II D p-branes. In many instances the kinetic terms are in fact modified by a term proportional to the scalar potential itself. This can be linked to the appearance of higher-dimensional supersymmetric operators correcting the Kähler potential. We identify the supersymmetric dimension-eight operators describing the α' corrections captured by the D-brane Dirac-Born-Infeld action. Our analysis then allows an embedding of the D-brane moduli effective action into an {N}=1 supergravity formulation. The effects of the potential-dependent kinetic terms may be very important if one of the scalars is the inflaton, since they lead to a flattening of the scalar potential. We analyze this flattening effect in detail and compute its impact on the CMB observables for single-field inflation with monomial potentials.

  18. 'Catching the waves' - slow cortical potentials as moderator of voluntary action.

    PubMed

    Schmidt, Stefan; Jo, Han-Gue; Wittmann, Marc; Hinterberger, Thilo

    2016-09-01

    The readiness potential is an ongoing negativity in the EEG preceding a self-initiated movement by approximately 1.5s. So far it has predominantly been interpreted as a preparatory signal with a causal link to the upcoming movement. Here a different hypothesis is suggested which we call the selective slow cortical potential sampling hypothesis. In this review of recent research results we argue that the initiation of a voluntary action is more likely during negative fluctuations of the slow cortical potential and that the sampling and averaging of many trials leads to the observed negativity. That is, empirical evidence indicates that the early readiness potential is not a neural correlate of preconscious motor preparation and thus a determinant of action. Our hypothesis thereafter challenges the classic interpretation of the Libet experiment which is often taken as proof that there is no free will. We furthermore suggest that slow cortical potentials are related to an urge to act but are not a neural indicator of the decision process of action initiation.

  19. Cortisol rapidly affects amplitudes of heartbeat-evoked brain potentials--implications for the contribution of stress to an altered perception of physical sensations?

    PubMed

    Schulz, André; Strelzyk, Florian; Ferreira de Sá, Diana S; Naumann, Ewald; Vögele, Claus; Schächinger, Hartmut

    2013-11-01

    Little is known about the impact of stress and stress hormones on the processing of visceral-afferent signals. Clinical data suggest that cortisol may lower the threshold for interoceptive stimuli, while a pharmacological administration of cortisol decreases the sensitivity for physical symptoms. To clarify the role of cortisol for the processing of interoceptive signals, we investigated 16 healthy men on two occasions, once during the infusion of 4 mg of cortisol and once during the infusion of a placebo substance. Heartbeat-evoked potentials (HEP; derived from resting EEG and ECG, during open and closed eyes), which are psychophysiological indicators for the cortical processing of cardioceptive signals, were measured over 6-min periods once before, and four times after the infusion (1-7, 11-17, 21-27 and 31-37 min). We found that HEP amplitudes were higher during open than during closed eyes between 1 and 17 min after cortisol infusion. There was no effect of cortisol on heart rate. We conclude that cortisol may rapidly modulate the cortical processing of cardioceptive neural signals. These results may have relevance for the effects of stress on the development and maintenance of psychosomatic symptoms.

  20. An experimental study on a function of the cupula. Effect of cupula removal on the ampullary nerve action potential.

    PubMed

    Suzuki, M; Harada, Y; Sugata, Y

    1984-01-01

    We used a posterior semicircular canal that had been isolated from a frog. From the utricular side the ampulla was cut open at a position one third of the way along the long axis. The cupula was removed through this opening using a glass micropipette. The action potential from the posterior ampullary nerve was recorded before and after removal of the cupula. After removal, the action potential disappeared almost completely. When the cupula was put back on the crista, the action potential was restored. When the cupula was put back upside down, the action potential recovered, but to a lesser extent.

  1. The mode of action of quinidine on isolated rabbit atria interpreted from intracellular potential records.

    PubMed

    VAUGHAN WILLIAMS, E M

    1958-09-01

    An attempt has been made to show why quinidine, which has long been known not to lengthen the duration of the cardiac action potential, measured with external electrodes, and also not to lengthen, and sometimes to shorten, the absolute refractory period, nevertheless reduces the maximum frequency at which atria can respond to a stimulus. Simultaneous measurements have been made in electrically driven isolated rabbit atria of contractions, conduction velocity and intracellular potentials before and during exposure to a wide range of concentrations of quinidine sulphate. The resting potential remained undiminished, in contrast to the effect of quinidine on Purkinje fibres. In the therapeutic range of doses, up to 10 mg./l., the half-time for repolarization was either shortened or unchanged, thus providing an explanation for the failure of quinidine to prolong the absolute refractory period. In contrast, even at low concentrations of quinidine, conduction velocity and the rate of rise of the action potential were greatly slowed, and the height of the overshoot was reduced. The terminal phase of the action potential was prolonged. It is known that the rate of rise of the action potential is a function of the level of repolarization at which an impulse takes off (the more negative the take-off point, the faster the rate of rise). Normally, a stimulus introduced when repolarization has proceeded to 2/3 of the resting potential evokes a response with a rate of rise fast enough for propagation, so that the duration of the terminal 1/3 of the phase of repolarization has no influence upon the length of the effective refractory period. In the presence of quinidine, however, the rate of rise itself was directly reduced, thus repolarization had to proceed further before the critical take-off point was reached at which the rate of rise was fast enough for propagation, and the duration of the terminal phase of repolarization thus became significant. It has been concluded that

  2. Recovery of the slow action potential is hastened by the calcium slow channel agonist, Bay-K-8644.

    PubMed

    Sada, H; Sada, S; Sperelakis, N

    1986-01-14

    Effects of the positive inotropic drug, Bay-K-8644, were studied on the slow action potential (AP) parameters and diastolic recovery of Vmax in K+ (22 mM)-depolarized rabbit papillary muscles. Bay-K-8644 (10(-6) M) increased the amplitude, maximum rate of rise (Vmax) and duration of the slow APs. Diastolic recovery of Vmax, examined by a paired-pulse protocol, was approximated by a single exponential function, both in control and in drug-treated muscles. The time constant of the recovery for drug-treated preparations was 171 +/- 20 ms (n = 9), and was significantly smaller than that for control: 414 +/- 45 ms (n = 12) (P less than 0.001). The diastolic intervals which allow 90% recovery of Vmax (T90%) were: 752 +/- 106 ms (n = 12) for control and 364 +/- 53 ms (n = 9) in the presence of drug, the latter being significantly shorter (P less than 0.01). The extent of the reductions in Vmax, at driving frequencies higher than 0.5 Hz, was minimal in the presence of the drug compared to the control. It was concluded that Bay-K-8644 not only enhanced the slow inward current, but also accelerated the reactivation process of the slow inward current and Ca2+ slow channel.

  3. Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

    PubMed

    Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro

    2014-11-01

    The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method.

  4. Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade

    PubMed Central

    Gainey, Melanie A.; Tatavarty, Vedakumar; Nahmani, Marc; Lin, Heather; Turrigiano, Gina G.

    2015-01-01

    Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up. PMID:26109571

  5. Event-related potentials reveal early activation of body part representations in action concept comprehension.

    PubMed

    Lu, Aitao; Liu, Jing; Zhang, John X

    2012-03-01

    With tasks involving action concept comprehension, many fMRI studies have reported brain activations in sensori-motor regions specific to effectors of the referent action. There is relatively less evidence whether such activations reflect early semantic access or late conceptual re-processing. Here we recorded event-related potentials when participants recognized noun-verb pairs. For Congruent pairs, the verb was the one most commonly associated with the noun (e.g., football-kick). Compared with a control condition, verbs in Congruent pairs showed priming effects in the time windows of 100-150 ms and 210-260 ms. Such activation seems to be specific to body part but not other aspects of the action as similar priming effect was also found when the noun and verb involved different actions though sharing the same body part (e.g., football-jump), documenting for the first time the early activation of body part representations in action concept comprehension. PMID:22306088

  6. Event-related potentials reveal early activation of body part representations in action concept comprehension.

    PubMed

    Lu, Aitao; Liu, Jing; Zhang, John X

    2012-03-01

    With tasks involving action concept comprehension, many fMRI studies have reported brain activations in sensori-motor regions specific to effectors of the referent action. There is relatively less evidence whether such activations reflect early semantic access or late conceptual re-processing. Here we recorded event-related potentials when participants recognized noun-verb pairs. For Congruent pairs, the verb was the one most commonly associated with the noun (e.g., football-kick). Compared with a control condition, verbs in Congruent pairs showed priming effects in the time windows of 100-150 ms and 210-260 ms. Such activation seems to be specific to body part but not other aspects of the action as similar priming effect was also found when the noun and verb involved different actions though sharing the same body part (e.g., football-jump), documenting for the first time the early activation of body part representations in action concept comprehension.

  7. Potentiators of Defective ΔF508-CFTR Gating that Do Not Interfere with Corrector Action.

    PubMed

    Phuan, Puay-Wah; Veit, Guido; Tan, Joseph A; Finkbeiner, Walter E; Lukacs, Gergely L; Verkman, A S

    2015-10-01

    Combination drug therapies under development for cystic fibrosis caused by the ∆F508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR) include a "corrector" to improve its cellular processing and a "potentiator" to improve its chloride channel function. Recently, it was reported that the approved potentiator N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (Ivacaftor) reduces ∆F508-CFTR cellular stability and the efficacy of investigational correctors, including 3-(6-[([1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl) amino]-3-methyl-2-pyridinyl)-benzoic acid and 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(2-hydroxy-1,1-dimethylethyl)-1H-indol-5-yl), which might contribute to the modest reported efficacy of combination therapy in clinical trials. Here, we report the identification and characterization of potentiators that do not interfere with ∆F508-CFTR stability or corrector action. High-throughput screening and structure-activity analysis identified several classes of potentiators that do not impair corrector action, including tetrahydrobenzothiophenes, thiooxoaminothiazoles, and pyrazole-pyrrole-isoxazoles. The most potent compounds have an EC(50) for ∆F508-CFTR potentiation down to 18 nM and do not reduce corrector efficacy in heterologous ∆F508-CFTR-expressing cells or primary cultures of ∆F508/∆F508 human bronchial epithelia. The ΔF508-CFTR potentiators also activated wild-type and G551D CFTR, albeit weakly. The efficacy of combination therapy for cystic fibrosis caused by the ∆F508 mutation may be improved by replacement of Ivacaftor with a potentiator that does not interfere with corrector action. PMID:26245207

  8. Iridium Oxide Nanotube Electrodes for Highly Sensitive and Prolonged Intracellular Measurement of Action Potentials

    PubMed Central

    Lin, Ziliang Carter; Xie, Chong; Osakada, Yasuko; Cui, Yi; Cui, Bianxiao

    2014-01-01

    Intracellular recording of action potentials is important to understand electrically-excitable cells. Recently, vertical nanoelectrodes have been developed to achieve highly sensitive, minimally invasive, and large scale intracellular recording. It has been demonstrated that the vertical geometry is crucial for the enhanced signal detection. Here we develop nanoelectrodes made up of nanotubes of iridium oxide. When cardiomyocytes are cultured upon those nanotubes, the cell membrane not only wraps around the vertical tubes but also protrudes deep into the hollow center. We show that this geometry enhances cell-electrode coupling and results in measuring much larger intracellular action potentials. The nanotube electrodes afford much longer intracellular access and are minimally invasive, making it possible to achieve stable recording up to an hour in a single session and more than 8 days of consecutive daily recording. This study suggests that the electrode performance can be significantly improved by optimizing the electrode geometry. PMID:24487777

  9. Post-tetanic mechanical tension and evoked action potentials in McArdle's disease

    PubMed Central

    Brandt, N. J.; Buchthal, F.; Ebbesen, F.; Kamieniecka, Z.; Krarup, C.

    1977-01-01

    The tension produced by the cramp evoked in the adductor pollicis muscle by repetitive stimuli to the nerve (20/s for 50 s) and by full voluntary effort in the brachial biceps was measured in a patient with McArdle's disease. The contracture was 17% of the peaktetanic tension, and was not associated with action potentials. Twitches superimposed on the contracture were at most diminished to half, as were their action potentials. Both slow and fast muscle fibres participated in the contracture. The contraction time of the twitches elicited after the tetanus was prolonged more in the patient than in a normal subject of the same age. There was evidence of delayed firing, first observed 90 seconds after the peak of the contracture. The patient had electromyographic and histological signs of myopathy. PMID:271684

  10. FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon

    PubMed Central

    Dover, Katarzyna; Marra, Christopher; Solinas, Sergio; Popovic, Marko; Subramaniyam, Sathyaa; Zecevic, Dejan; D'Angelo, Egidio; Goldfarb, Mitchell

    2016-01-01

    Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials. In addition, leak conductance density along the distal axon is estimated as <1% that of somatodendritic membrane. The faster inactivation rate of FHF-free Navs together with very low axonal leak conductance serves to minimize ionic fluxes and energetic demand during repetitive spike conduction and at rest. The absence of FHFs from Navs at nodes of Ranvier in the central nervous system suggests a similar mechanism of current flux minimization along myelinated axons. PMID:27666389

  11. Attention-dependent reductions in burstiness and action potential height in macaque area V4

    PubMed Central

    Anderson, Emily B.; Mitchell, Jude F.; Reynolds, John H.

    2013-01-01

    Attention improves the encoding of visual stimuli. One mechanism that is implicated in facilitating sensory encoding is the firing of action potentials in bursts. We tested the hypothesis that when spatial attention is directed to a stimulus, this causes an increase in burst firing to the attended stimulus. To the contrary, we found an attention-dependent reduction in burstiness among putative pyramidal neurons in macaque area V4. We accounted for this using a conductance-based Hodgkin-Huxley style model in which attentional modulation stems from scaling excitation and inhibition. The model exhibited attention-dependent increases in firing rate and made the surprising and correct prediction that when attention is directed into a neuron’s receptive field, this reduces action potential height. The model thus provided a unified explanation for three distinct forms of attentional modulation, two of them novel, and implicates scaling of the responses of excitatory and inhibitory input populations in mediating attention. PMID:23852114

  12. Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing

    PubMed Central

    Ford, Marc C.; Alexandrova, Olga; Cossell, Lee; Stange-Marten, Annette; Sinclair, James; Kopp-Scheinpflug, Conny; Pecka, Michael; Attwell, David; Grothe, Benedikt

    2015-01-01

    Action potential timing is fundamental to information processing; however, its determinants are not fully understood. Here we report unexpected structural specializations in the Ranvier nodes and internodes of auditory brainstem axons involved in sound localization. Myelination properties deviated significantly from the traditionally assumed structure. Axons responding best to low-frequency sounds had a larger diameter than high-frequency axons but, surprisingly, shorter internodes. Simulations predicted that this geometry helps to adjust the conduction velocity and timing of action potentials within the circuit. Electrophysiological recordings in vitro and in vivo confirmed higher conduction velocities in low-frequency axons. Moreover, internode length decreased and Ranvier node diameter increased progressively along the distal axon segments, which simulations show was essential to ensure precisely timed depolarization of the giant calyx of Held presynaptic terminal. Thus, individual anatomical parameters of myelinated axons can be tuned to optimize pathways involved in temporal processing. PMID:26305015

  13. Real-time imaging of action potentials in nerves using changes in birefringence

    PubMed Central

    Badreddine, Ali H.; Jordan, Tomas; Bigio, Irving J.

    2016-01-01

    Polarized light can be used to measure the electrical activity associated with action potential propagation in nerves, as manifested in simultaneous dynamic changes in their intrinsic optical birefringence. These signals may serve as a tool for minimally invasive neuroimaging in various types of neuroscience research, including the study of neuronal activation patterns with high spatiotemporal resolution. A fast linear photodiode array was used to image propagating action potentials in an excised portion of the lobster walking leg nerve. We show that the crossed-polarized signal (XPS) can be reliably imaged over a ≥2 cm span in our custom nerve chamber, by averaging multiple-stimulation signals, and also in single-scan real-time “movies”. This demonstration paves the way toward utilizing changes in the optical birefringence to image more complex neuronal activity in nerve fibers and other organized neuronal tissue. PMID:27231635

  14. Real-time imaging of action potentials in nerves using changes in birefringence.

    PubMed

    Badreddine, Ali H; Jordan, Tomas; Bigio, Irving J

    2016-05-01

    Polarized light can be used to measure the electrical activity associated with action potential propagation in nerves, as manifested in simultaneous dynamic changes in their intrinsic optical birefringence. These signals may serve as a tool for minimally invasive neuroimaging in various types of neuroscience research, including the study of neuronal activation patterns with high spatiotemporal resolution. A fast linear photodiode array was used to image propagating action potentials in an excised portion of the lobster walking leg nerve. We show that the crossed-polarized signal (XPS) can be reliably imaged over a ≥2 cm span in our custom nerve chamber, by averaging multiple-stimulation signals, and also in single-scan real-time "movies". This demonstration paves the way toward utilizing changes in the optical birefringence to image more complex neuronal activity in nerve fibers and other organized neuronal tissue. PMID:27231635

  15. Changes in cochlear responses in guinea pig with changes in perilymphatic K+. Part I: summating potentials, compound action potentials and DPOAEs.

    PubMed

    Marcon, Simon; Patuzzi, Robert

    2008-03-01

    We have measured the effects of changing perilymphatic K+ by perfusing scala tympani in guinea pigs with salt solutions high or low in K+, while monitoring the distortion product otoacoustic emissions (DPOAEs) in the ear canal (a measure of mechanical vibration of the organ of Corti), the summating potential (SP) evoked by high-frequency tone-bursts (taken to be a measure of pre-synaptic electrical activity of the inner hair cells) and the compound action potential (CAP) of the auditory nerve (taken to be a measure of post-synaptic neural activity). We have attempted to investigate the osmotic effects of our perfusates by comparison with simple hyperosmotic sucrose perfusates and iso-osmotic versions of perfusates, and for the effects of changes in other ions (e.g. Na+ and Cl-) by keeping these constant in some perfusates while elevating K+. We have found that changing the K+ concentration over the range 0-30mM elevated the SP and CAP thresholds almost equally in normal animals, and not at all in animals devoid of outer hair cells (OHCs), showing that OHCs are sensitive to the perfusates we have used, but the inner hair cells (IHCs) and the type I afferent dendrites are not, presumably because IHCs are shielded from perilymph by supporting cells, and the membranes of the afferent dendrite membranes exposed directly to our perfusates are dominated by Cl(-) permeability, rather than by K+ permeability. This view is supported by experiments in which the perilymphatic Cl(-) concentration was reduced, producing a large elevation in CAP threshold, but a much smaller elevation of SP threshold, suggesting disruption of action potential initiation. The view that threshold elevations with changes in perilymphatic K+ are due almost solely to a disruption of OHC function and a consequent change in the mechanical sensitivity of the organ of Corti was supported by measurements of amplitude of the 2f1-f2 distortion product otoacoustic emission. During elevations in K+, DPOAEs

  16. Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a+/− hearts

    PubMed Central

    Matthews, Gareth D K; Guzadhur, Laila; Sabir, Ian N; Grace, Andrew A; Huang, Christopher L-H

    2013-01-01

    Reductions in cardiac action potential wavelength, and the consequent wavebreak, have been implicated in arrhythmogenesis. Tachyarrhythmias are more common in the Brugada syndrome, particularly following pharmacological challenge, previously modelled using Scn5a+/− murine hearts. Propagation latencies and action potential durations (APDs) from monophasic action potential recordings were used to assess wavelength changes with heart rate in Langendorff-perfused wild-type (WT) and Scn5a+/− hearts. Recordings were obtained from right (RV) and left (LV) ventricular, epicardial and endocardial surfaces during incremental pacing, before and following flecainide or quinidine challenge. Conduction velocities (θ′), action potential wavelengths (λ′= APD ×θ′), and their corresponding alternans depended non-linearly upon diastolic interval (DI). Maximum θ′ was lower in Scn5a+/− RV epicardium than endocardium. Flecainide further reduced θ′, accentuating this RV conduction block. Quinidine reduced maximum θ′ in WT and caused earlier conduction failure in the RV of both Scn5a+/− and WT. Use of recovery wavelengths (λ′0= DI ×θ′) rather than DI, provided novel λ restitution plots of λ′ against λ′0, which sum to a basic cycle distance permitting feedback analysis. λ′ restitution gradient better correlated with alternans magnitude than either APD or θ restitution gradient. The large differences in θ′ and APD restitution contrasted with minor differences in maximum λ′ between epi- and endocardia of untreated hearts, and quinidine-treated WT hearts. Strikingly, all regions and conditions converged to a common instability point, implying a conserved relationship. Flecainide or quinidine decreased the pacing rates at which this occurred, through reducing basic cycle distance, in the Scn5a+/− RV epicardium, directly predictive of its arrhythmic phenotype. PMID:23836691

  17. Noisy unmaskers of multistability of periodic rhythms in a model of the ventricular cardiac action potential

    NASA Astrophysics Data System (ADS)

    Surovyatkina, Elena; Egorchenkov, Roman; Ivanov, Guennady

    2007-06-01

    The coexistence of different dynamical regimes of cardiac cell-model at a fixed set of stimulation parameters, i.e. multistability, revealed by noise is presented in this paper. Numerical simulations are performed using Luo-Rudy (LR1) action potential model. Numerical experiments with LR1 model conducted via noisy periodical stimulation showed the coexistence of several periodic rhythms. Weak noise in period of stimulation causes a hopping process between all the (meta-) stable rhythms of cell-model. This process is reflected in several parallel branches of the bifurcation diagram: noise unveils new, invisible before, stable rhythms which could appear in this model at different initial conditions. The phenomenon of multistability is directly evidenced by other numerical experiments: we have established the multistability property of a cell consisting in the fact that different initial conditions of stimulation (different extrasystole application times) lead to different stable periodic rhythms. We have obtained the shaping of attraction basins on the action potential curves. Such basins of attraction contain a set of initial conditions which determinate a stable periodic rhythm. We have found a close association between the attraction basins of the complex rhythms on the curves of action potential and the cardiac vulnerable windows on ECG record, during which extra stimuli can induce life threatening arrhythmias. Obtained results allow us to make a conclusion that multistability is very important for the electrical conduction system of the heart from the cell level to the integrated function of the heart.

  18. Seasonal variation in conduction velocity of action potentials in squid giant axons.

    PubMed

    Rosenthal, J J; Bezanilla, F

    2000-10-01

    To determine whether the electrical properties of the squid giant axon are seasonally acclimated, action potentials, recorded at different temperatures, were compared between giant axons isolated from Loligo pealei caught in May, from relatively cold waters (approximately 10 degrees-12 degrees C), and in August, from relatively warm waters (approximately 20 degrees C). Parameters relating to the duration of the action potential (e.g., maximum rate of rise, maximum rate of fall, and duration at half-peak) did not change seasonally. The relationship between conduction velocity and temperature remained constant between seasons as well, in spite of the fact that May axons were significantly larger than August axons. When normalized to the fiber diameter, mean May conduction velocities were 83% of the August values at all temperatures tested, and analysis of the rise time of the action potential foot suggested that a change in the axoplasmic resistivity was responsible for this difference. Direct measurements of axoplasmic resistance further supported this hypothesis. Thus seasonal changes in the giant axon's size and resistivity are not consistent with compensatory thermal acclimation, but instead serve to maintain a constant relationship between conduction velocity and temperature.

  19. ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

    PubMed

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-01-01

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis. PMID:27649160

  20. ER Stress-Mediated Signaling: Action Potential and Ca2+ as Key Players

    PubMed Central

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-01-01

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca2+) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca2+ regulates cell death both at the early and late stages of apoptosis. Severe Ca2+ dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca2+ (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca2+ and action potential in ER stress-mediated apoptosis. PMID:27649160

  1. The electrogenic Na+/HCO3− cotransport modulates resting membrane potential and action potential duration in cat ventricular myocytes

    PubMed Central

    Villa-Abrille, María C; Petroff, Martín G Vila; Aiello, Ernesto A

    2007-01-01

    Perforated whole-cell configuration of patch clamp was used to determine the contribution of the electrogenic Na+/HCO3− cotransport (NBC) on the shape of the action potential in cat ventricular myocytes. Switching from Hepes to HCO3− buffer at constant extracellular pH (pHo) hyperpolarized resting membrane potential (RMP) by 2.67 ± 0.42 mV (n = 9, P < 0.05). The duration of action potential measured at 50% of repolarization time (APD50) was 35.8 ± 6.8% shorter in the presence of HCO3− than in its absence (n = 9, P < 0.05). The anion blocker SITS prevented and reversed the HCO3−-induced hyperpolarization and shortening of APD. In addition, no HCO3−-induced hyperpolarization and APD shortening was observed in the absence of extracellular Na+. Quasi-steady-state currents were evoked by 8 s duration voltage-clamped ramps ranging from −130 to +30 mV. A novel component of SITS-sensitive current was observed in the presence of HCO3−. The HCO3−-sensitive current reversed at −87 ± 5 mV (n = 7), a value close to the expected reversal potential of an electrogenic Na+/HCO3− cotransport with a HCO3−:Na+ stoichiometry ratio of 2: 1. The above results allow us to conclude that the cardiac electrogenic Na+/HCO3− cotransport has a relevant influence on RMP and APD of cat ventricular cells. PMID:17138608

  2. Carbon nanotube multi-electrode array chips for noninvasive real-time measurement of dopamine, action potentials, and postsynaptic potentials.

    PubMed

    Suzuki, Ikuro; Fukuda, Mao; Shirakawa, Keiichi; Jiko, Hideyasu; Gotoh, Masao

    2013-11-15

    Multi-electrode arrays (MEAs) can be used for noninvasive, real-time, and long-term recording of electrophysiological activity and changes in the extracellular chemical microenvironment. Neural network organization, neuronal excitability, synaptic and phenotypic plasticity, and drug responses may be monitored by MEAs, but it is still difficult to measure presynaptic activity, such as neurotransmitter release, from the presynaptic bouton. In this study, we describe the development of planar carbon nanotube (CNT)-MEA chips that can measure both the release of the neurotransmitter dopamine as well as electrophysiological responses such as field postsynaptic potentials (fPSPs) and action potentials (APs). These CNT-MEA chips were fabricated by electroplating the indium-tin oxide (ITO) microelectrode surfaces. The CNT-plated ITO electrode exhibited electrochemical response, having much higher current density compared with the bare ITO electrode. Chronoamperometric measurements using these CNT-MEA chips detected dopamine at nanomolar concentrations. By placing mouse striatal brain slices on the CNT-MEA chip, we successfully measured synaptic dopamine release from spontaneous firings with a high S/N ratio of 62. Furthermore, APs and fPSPs were measured from cultured hippocampal neurons and slices with high temporal resolution and a 100-fold greater S/N ratio. Our CNT-MEA chips made it possible to measure neurotransmitter dopamine (presynaptic activities), postsynaptic potentials, and action potentials, which have a central role in information processing in the neuronal network. CNT-MEA chips could prove useful for in vitro studies of stem cell differentiation, drug screening and toxicity, synaptic plasticity, and pathogenic processes involved in epilepsy, stroke, and neurodegenerative diseases. PMID:23774164

  3. Selective potentiation of (α4)3(β2)2 nicotinic acetylcholine receptors augments amplitudes of prefrontal acetylcholine- and nicotine-evoked glutamatergic transients in rats.

    PubMed

    Grupe, Morten; Paolone, Giovanna; Jensen, Anders A; Sandager-Nielsen, Karin; Sarter, Martin; Grunnet, Morten

    2013-11-15

    Prefrontal glutamate release evoked through activation of α4β2* nicotinic acetylcholine receptors (nAChRs) situated on thalamic glutamatergic afferents mediates cue detection processes and thus contributes to attentional performance. However, little is known about the respective contributions of the high sensitivity and low sensitivity (LS) stoichiometries of the α4β2 nAChR, (α4)2(β2)3 and (α4)3(β2)2, to these processes. In the present study we employed glutamate-sensitive microelectrodes and the (α4)3(β2)2-selective positive allosteric modulator (PAM) NS9283 to investigate the importance of the LS α4β2 nAChR for glutamate release in the rat medial prefrontal cortex (mPFC). Firstly, the signaling evoked by physiologically relevant ACh concentrations through the (α4)3(β2)2 nAChR in HEK293 cells was potentiated by NS9283, consistent with the classification of NS9283 as a PAM. In urethane-anesthetized rats, intra-prefrontal pressure ejections of NS9283 evoked glutamatergic transients. Importantly, this glutamate release was attenuated by removal of cholinergic projections to the recording area. This finding indicates that the effects of NS9283 depend on endogenous ACh, again consistent with effects of a PAM. We then conducted microdialysis to demonstrate the presence of extracellular ACh in urethane-anesthetized control rats. While detectable, those levels were significantly lower than in awake rats. Finally, the amplitudes of glutamatergic transients evoked by local pressure ejections of a low concentration of nicotine were significantly augmented following systemic administration of NS9283 (3.0mg/kg). In conclusion, our results indicate that a LS α4β2 nAChR PAM such as NS9283 may enhance the cholinergic modulation of glutamatergic neurotransmission in the cortex, thereby perhaps alleviating the attentional impairments common to a range of brain disorders.

  4. Selective potentiation of (α4)3(β2)2 nicotinic acetylcholine receptors augments amplitudes of prefrontal acetylcholine- and nicotine-evoked glutamatergic transients in rats

    PubMed Central

    Grupe, Morten; Paolone, Giovanna; Jensen, Anders A.; Sandager-Nielsen, Karin; Sarter, Martin; Grunnet, Morten

    2013-01-01

    Prefrontal glutamate release evoked through activation of α4β2* nicotinic acetylcholine receptors (nAChRs) situated on thalamic glutamatergic afferents mediates cue detection processes and thus contributes to attentional performance. However, little is known about the respective contributions of the high sensitivity and low sensitivity (LS) stoichiometries of the α4β2 nAChR, (α4)2(β2)3 and (α4)3(β2)2, to these processes. In the present study we employed glutamate-sensitive microelectrodes and the (α4)3(β2)2-selective positive allosteric modulator (PAM) NS9283 to investigate the importance of the LS α4β2 nAChR for glutamate release in the rat medial prefrontal cortex (mPFC). Firstly, the signaling evoked by physiologically relevant ACh concentrations through the (α4)3(β2)2 nAChR in HEK293 cells was potentiated by NS9283, consistent with the classification of NS9238 as a PAM. In urethane-anesthetized rats, intra-prefrontal pressure ejections of NS9283 evoked glutamatergic transients. Importantly, this glutamate release was attenuated by removal of cholinergic projections to the recording area. This finding indicates that the effects of NS9283 depend on endogenous ACh, again consistent with effects of a PAM. We then conducted microdialysis to demonstrate the presence of extracellular ACh in urethane-anesthetized control rats. While detectable, those levels were significantly lower than in awake rats. Finally, the amplitudes of glutamatergic transients evoked by local pressure ejections of a low concentration of nicotine were significantly augmented following systemic administration of NS9283 (3.0 mg/kg). In conclusion, our results indicate that a LS α4β2 nAChR PAMs such as NS9283 may enhance the cholinergic modulation of glutamatergic neurotransmission in the cortex, thereby perhaps alleviating the attentional impairments common to a range of brain disorders. PMID:24051136

  5. ACTION-SPACE CLUSTERING OF TIDAL STREAMS TO INFER THE GALACTIC POTENTIAL

    SciTech Connect

    Sanderson, Robyn E.; Helmi, Amina; Hogg, David W.

    2015-03-10

    We present a new method for constraining the Milky Way halo gravitational potential by simultaneously fitting multiple tidal streams. This method requires three-dimensional positions and velocities for all stars to be fit, but does not require identification of any specific stream or determination of stream membership for any star. We exploit the principle that the action distribution of stream stars is most clustered when the potential used to calculate the actions is closest to the true potential. Clustering is quantified with the Kullback-Leibler Divergence (KLD), which also provides conditional uncertainties for our parameter estimates. We show, for toy Gaia-like data in a spherical isochrone potential, that maximizing the KLD of the action distribution relative to a smoother distribution recovers the input potential. The precision depends on the observational errors and number of streams; using K III giants as tracers, we measure the enclosed mass at the average radius of the sample stars accurate to 3% and precise to 20%-40%. Recovery of the scale radius is precise to 25%, biased 50% high by the small galactocentric distance range of stars in our mock sample (1-25 kpc, or about three scale radii, with mean 6.5 kpc). 20-25 streams with at least 100 stars each are required for a stable confidence interval. With radial velocities (RVs) to 100 kpc, all parameters are determined with ∼10% accuracy and 20% precision (1.3% accuracy for the enclosed mass), underlining the need to complete the RV catalog for faint halo stars observed by Gaia.

  6. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential.

    PubMed

    Desbois, Andrew P; Smith, Valerie J

    2010-02-01

    Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.

  7. Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.

    PubMed Central

    Taggart, P; Sutton, P; John, R; Lab, M; Swanton, H

    1992-01-01

    OBJECTIVE--The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS--Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS--23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING--Tertiary referral centre for cardiology. RESULTS--In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal

  8. Potentiation of antimalarial drug action by chlorpheniramine against multidrug-resistant Plasmodium falciparum in vitro.

    PubMed

    Nakornchai, Sunan; Konthiang, Phattanapong

    2006-09-01

    Chlorpheniramine, a histamine H1 receptor antagonist, was assayed for in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum K1 strain and chloroquine-resistant P. falciparum T9/94 clone, by measuring the 3H-hypoxanthine incorporation. Chlorphenirame inhibited P. falciparum K1 and T9/94 growth with IC50 values of 136.0+/-40.2 microM and 102.0+/-22.6 microM respectively. A combination of antimalarial drug and chlorpheniramine was tested against resistant P. falciparum in vitro. Isobologram analysis showed that chlorpheniramine exerts marked synergistic action on chloroquine against P. falciparum K1 and T9/94. Chlorpheniramine also potentiated antimalarial action of mefloquine, quinine or pyronaridine against both of the resistant strains of P. falciparum. However, chlorpheniramine antagonism with artesunate was obtained in both P. falciparum K1 and T9/94. The results in this study indicate that antihistaminic drugs may be promising candidates for potentiating antimalarial drug action against drug resistant malarial parasites.

  9. Xenin-25 Potentiates Glucose-dependent Insulinotropic Polypeptide Action via a Novel Cholinergic Relay Mechanism*

    PubMed Central

    Wice, Burton M.; Wang, Songyan; Crimmins, Dan L.; Diggs-Andrews, Kelly A.; Althage, Matthew C.; Ford, Eric L.; Tran, Hung; Ohlendorf, Matthew; Griest, Terry A.; Wang, Qiuling; Fisher, Simon J.; Ladenson, Jack H.; Polonsky, Kenneth S.

    2010-01-01

    The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, “GIP/DT” animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the β-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in β-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM. PMID:20421298

  10. Xenin-25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism.

    PubMed

    Wice, Burton M; Wang, Songyan; Crimmins, Dan L; Diggs-Andrews, Kelly A; Althage, Matthew C; Ford, Eric L; Tran, Hung; Ohlendorf, Matthew; Griest, Terry A; Wang, Qiuling; Fisher, Simon J; Ladenson, Jack H; Polonsky, Kenneth S

    2010-06-25

    The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, "GIP/DT" animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the beta-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in beta-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM. PMID:20421298

  11. Phasic changes in intracellular pH during action potentials of sheep Purkinje fibres.

    PubMed

    Pressler, M L

    1988-01-01

    Regulation of intracellular pH (pHi) and the relationship between H+ and Ca2+ may vary during activity. Ion-selective microelectrodes were used to record pHi during action potentials of sheep Purkinje fibres prolonged by low temperature (21 degrees C) and elevated CO2 content. Intracellular pH also was measured during changes in extracellular calcium concentration, [Ca2+]o. Cytosolic alkalinization (peak pHi change, 0.03-0.05) was observed during the long action-potential plateau and transient acidification (0.01-0.02 units) upon repolarization. Potassium-induced depolarization to plateau potentials (i.e. to -15 +/- 2 mV) simulated the peak magnitude of the alkalinization. However, compensation for the alkalinization occurred at a faster rate during the action potential (8.9 +/- 4.3 nM/min) than during K+ depolarization (1.2 +/- 0.5 nM/min). In comparison, the cytoplasm acidified in resting fibres (0.06-0.07 log units) during changes of [Ca2+]o thought to increase intracellular calcium concentration. Alterations of pHi were translated into changes of proton concentration ([H+]i). Ten- to twenty-fold elevation of [Ca2+]o evoked a comparable change in [H+]i (mean increase, 5.7 nM) but oppositely directed from that during the plateau (mean decrease, 8.8 nM). The findings in resting fibres seem consistent with displacement of bound protons by Ca2+. In contrast, the initial change in pHi during the plateau is proposed to be consequent to Ca2+-release from sarcoplasmic reticulum and/or phosphocreatine hydrolysis coupled to ATP regeneration.

  12. Small amplitude quasibreathers and oscillons

    SciTech Connect

    Fodor, Gyula; Lukacs, Arpad; Forgacs, Peter; Horvath, Zalan

    2008-07-15

    Quasibreathers (QB) are time-periodic solutions with weak spatial localization introduced in G. Fodor et al. in [Phys. Rev. D 74, 124003 (2006)]. QB's provide a simple description of oscillons (very long-living spatially localized time dependent solutions). The small amplitude limit of QB's is worked out in a large class of scalar theories with a general self-interaction potential, in D spatial dimensions. It is shown that the problem of small amplitude QB's is reduced to a universal elliptic partial differential equation. It is also found that there is the critical dimension, D{sub crit}=4, above which no small amplitude QB's exist. The QB's obtained this way are shown to provide very good initial data for oscillons. Thus these QB's provide the solution of the complicated, nonlinear time dependent problem of small amplitude oscillons in scalar theories.

  13. Effect of autonomic blocking agents on the respiratory-related oscillations of ventricular action potential duration in humans

    PubMed Central

    van Duijvenboden, Stefan; Hanson, Ben; Child, Nick; Orini, Michele; Rinaldi, Christopher A.; Gill, Jaswinder S.

    2015-01-01

    Ventricular action potential duration (APD) is an important component of many physiological functions including arrhythmogenesis. APD oscillations have recently been reported in humans at the respiratory frequency. This study investigates the contribution of the autonomic nervous system to these oscillations. In 10 patients undergoing treatment for supraventricular arrhythmias, activation recovery intervals (ARI; a conventional surrogate for APD) were measured from multiple left and right ventricular (RV) endocardial sites, together with femoral artery pressure. Respiration was voluntarily regulated and heart rate clamped by RV pacing. Sympathetic and parasympathetic blockade was achieved using intravenous metoprolol and atropine, respectively. Metroprolol reduced the rate of pressure development (maximal change in pressure over time): 1,271 (± 646) vs. 930 (± 433) mmHg/s; P < 0.01. Systolic blood pressure (SBP) showed a trend to decrease after metoprolol, 133 (± 21) vs. 128 (± 25) mmHg; P = 0.06, and atropine infusion, 122 (± 26) mmHg; P < 0.05. ARI and SBP exhibited significant cyclical variations (P < 0.05) with respiration in all subjects with peak-to-peak amplitudes ranging between 0.7 and 17.0 mmHg and 1 and 16 ms, respectively. Infusion of metoprolol reduced the mean peak-to-peak amplitude [ARI, 6.2 (± 1.4) vs. 4.4 (± 1.0) ms, P = 0.008; SBP, 8.4 (± 1.6) vs. 6.2 (± 2.0) mmHg, P = 0.002]. The addition of atropine had no significant effect. ARI, SBP, and respiration showed significant coupling (P < 0.05) at the breathing frequency in all subjects. Directed coherence from respiration to ARI was high and reduced after metoprolol infusion [0.70 (± 0.17) vs. 0.50 (± 0.23); P < 0.05]. These results suggest a role of respiration in modulating the electrophysiology of ventricular myocardium in humans, which is partly, but not totally, mediated by β-adrenergic mechanisms. PMID:26475587

  14. Effects of bath resistance on action potentials in the squid giant axon: myocardial implications.

    PubMed Central

    Wu, J; Wikswo, J P

    1997-01-01

    This study presents a simplified version of the quasi-one-dimensional theory (Wu, J., E. A. Johnson, and J. M. Kootsey. 1996. A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle. Biophys. J. 71:2427-2439) with two components of the extracellular current, along and perpendicular to the axis, and a simulation and its experimental confirmation for the giant axon of the squid. By extending the one-dimensional core conductor cable equations, this theory predicts, as confirmed by the experiment, that the shapes of the intracellular and the extracellular action potentials are related to the resistance of the bath. Such a result was previously only expected by the field theories. The correlation between the shapes of the intracellular and the extracellular potentials of the giant axon of the squid resembles that observed during the anisotropic propagation of excitation in cardiac muscle. Therefore, this study not only develops a quasi-one-dimensional theory for a squid axon, but also provides one possible factor contributing to the anisotropic propagation of action potentials in cardiac muscle. PMID:9370430

  15. Effects of bath resistance on action potentials in the squid giant axon: myocardial implications.

    PubMed

    Wu, J; Wikswo, J P

    1997-11-01

    This study presents a simplified version of the quasi-one-dimensional theory (Wu, J., E. A. Johnson, and J. M. Kootsey. 1996. A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle. Biophys. J. 71:2427-2439) with two components of the extracellular current, along and perpendicular to the axis, and a simulation and its experimental confirmation for the giant axon of the squid. By extending the one-dimensional core conductor cable equations, this theory predicts, as confirmed by the experiment, that the shapes of the intracellular and the extracellular action potentials are related to the resistance of the bath. Such a result was previously only expected by the field theories. The correlation between the shapes of the intracellular and the extracellular potentials of the giant axon of the squid resembles that observed during the anisotropic propagation of excitation in cardiac muscle. Therefore, this study not only develops a quasi-one-dimensional theory for a squid axon, but also provides one possible factor contributing to the anisotropic propagation of action potentials in cardiac muscle.

  16. An Excel-based implementation of the spectral method of action potential alternans analysis.

    PubMed

    Pearman, Charles M

    2014-12-01

    Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro-arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T-wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results.

  17. Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles.

    PubMed

    Tucker, Kristal R; Block, Ethan R; Levitan, Edwin S

    2015-08-11

    Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H(+)-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca(2+)-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP(+)), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H(+) countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs.

  18. Carbon monoxide effects on human ventricle action potential assessed by mathematical simulations

    PubMed Central

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R.

    2013-01-01

    Carbon monoxide (CO) that is produced in a number of different mammalian tissues is now known to have significant effects on the cardiovascular system. These include: (i) vasodilation, (ii) changes in heart rate and strength of contractions, and (iii) modulation of autonomic nervous system input to both the primary pacemaker and the working myocardium. Excessive CO in the environment is toxic and can initiate or mediate life threatening cardiac rhythm disturbances. Recent reports link these ventricular arrhythmias to an increase in the slowly inactivating, or “late” component of the Na+ current in the mammalian heart. The main goal of this paper is to explore the basis of this pro-arrhythmic capability of CO by incorporating changes in CO-induced ion channel activity with intracellular signaling pathways in the mammalian heart. To do this, a quite well-documented mathematical model of the action potential and intracellular calcium transient in the human ventricular myocyte has been employed. In silico iterations based on this model provide a useful first step in illustrating the cellular electrophysiological consequences of CO that have been reported from mammalian heart experiments. Specifically, when the Grandi et al. model of the human ventricular action potential is utilized, and after the Na+ and Ca2+ currents in a single myocyte are modified based on the experimental literature, early after-depolarization (EAD) rhythm disturbances appear, and important elements of the underlying causes of these EADs are revealed/illustrated. Our modified mathematical model of the human ventricular action potential also provides a convenient digital platform for designing future experimental work and relating these changes in cellular cardiac electrophysiology to emerging clinical and epidemiological data on CO toxicity. PMID:24146650

  19. Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles

    PubMed Central

    Tucker, Kristal R.; Block, Ethan R.; Levitan, Edwin S.

    2015-01-01

    Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H+-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca2+-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP+), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H+ countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs. PMID:26216995

  20. Dynamical speckles patterns of action potential transmission effects in squid giant axon membrane

    NASA Astrophysics Data System (ADS)

    Llovera-González, Juan J.; Moreno-Yeras, Alfredo B.; Muramatsu, Mikiya; Soga, Diogo; Serra-Toledo, Rolando L.; Magalhães, Daniel S. F.

    2013-11-01

    Undoubtedly the most important result of the investigations in physiology and biophysics was the discovery of the electrochemical mechanism of propagation of the action potential in nerves that was made by Hodgkin and Huxley during the first half of the past century. Since some decades ago diverse experiments about the electro optical properties of the axon membrane there was published using the most diverse optical experimental procedures6-10. In this paper some results of a dynamical speckle technique applied for obtaining microscopic images of a section of a squid giant axon membrane during the activation by electrical impulses and his digital process are presented.

  1. Rapid local synchronization of action potentials: toward computation with coupled integrate-and-fire neurons.

    PubMed Central

    Hopfield, J J; Herz, A V

    1995-01-01

    The collective behavior of interconnected spiking nerve cells is investigated. It is shown that a variety of model systems exhibit the same short-time behavior and rapidly converge to (approximately) periodic firing patterns with locally synchronized action potentials. The dynamics of one model can be described by a downhill motion on an abstract energy landscape. Since an energy landscape makes it possible to understand and program computation done by an attractor network, the results will extend our understanding of collective computation from models based on a firing-rate description to biologically more realistic systems with integrate-and-fire neurons. Images Fig. 2 PMID:7624307

  2. Two Decades of Advances in High-Resolution Spectroscopy of Large-Amplitude Motions in N-Fold Potential Wells, as Illustrated by Methanol

    NASA Astrophysics Data System (ADS)

    Xu, Li-Hong

    2016-06-01

    Methanol is a simple and intensively studied organic molecule possessing one large-amplitude torsional motion. It has, for nearly a century, been a favorite of researchers in many fields, e.g., instrument builders, for whom methanol is often the first molecule chosen for testing an improved or a newly built instrument (including HIFI, the Heterodyne Instrument for the Far Infrared on board the Herschel space mission); theorists and/or dynamicists studying the challenging effects of a large-amplitude motion coupling with small-amplitude motions to enhance intramolecular vibrational energy redistribution; astronomers who have elevated methanol to their #1 interstellar weed because of its rich and omnipresent spectrum in the interstellar garden, where it serves as a unique probe for diagnosing conditions in star-forming regions; astrochemists studying isotopic ratios as clues to the chemical evolution of the universe; and fundamentalists seeking possible time variation of the proton/electron mass ratio in the standard model; just to name a few. From high-resolution to high-precision spectroscopy, the large-amplitude internal rotation of the methyl top against its OH framework in methanol has never failed to produce new surprises in spectral regions from the microwave all the way to the near IR. The very recent observation of completely unexpected large methanol hyperfine splittings is a vivid testimonial that the large-amplitude torsional motion can still lead us to unexplored landscapes. This talk will focus on the complicated vibration-torsion-rotation energy networks and interactions deduced from high resolution spectra; our efforts to understand some of them using ab-initio-assisted approaches and the modeling of torsion-rotation and torsionally mediated spin-rotation hyperfine splittings in methanol. These topics represent one part of the much larger fascinating world inhabited by methanolics.

  3. Effects of calcium channel antagonists on action potential conduction and transmitter release in the guinea-pig vas deferens.

    PubMed Central

    Beattie, D. T.; Cunnane, T. C.; Muir, T. C.

    1986-01-01

    The effects of the Ca2+ channel antagonists amlodipine, cobalt, diltiazem, nifedipine and verapamil and the local anaesthetic lignocaine were investigated on action potential conduction in and on evoked transmitter release from sympathetic nerves in the guinea-pig isolated vas deferens. Transmitter release was investigated by measurement of evoked (trains of pulses at 1 and 2 Hz, 0.1-0.5 ms supramaximal voltage) excitatory junction potentials (e.j.ps) using microelectrodes; tension was recorded simultaneously; tritium [3H] overflow from vasa preincubated (37 degrees C, 30 min) in Krebs solution containing either [3H]-noradrenaline (NA, 25 microCi ml-1, 2 X 10(-6) M NA) or [3H]-adenosine (50 microCi ml-1, 1 X 10(-6) M adenosine). Amlodipine (0.5-2 X 10(-4) M), verapamil (0.5-2 X 10(-4) M), diltiazem (1-8 X 10(-4) M), lignocaine (0.1-2 X 10(-3) M) and cobalt (2-6 X 10(-2) M) in descending order of potency, but not nifedipine (1-5 X 10(-3) M), increased the latency and inhibited, then abolished, the amplitude and number of action potentials in a concentration-dependent manner. Amlodipine (0.5-1 X 10(-4) M), verapamil (1-2 X 10(-4) M), diltiazem (1-5 X 10(-4) M) and cobalt (1 X 10(-3) M), in descending order of potency, but not nifedipine (5 X 10(-4) M), inhibited then abolished evoked e.j.ps in a concentration-dependent manner. Cobalt inhibited e.j.ps at a lower concentration than that (2-6 X 10(-2) M) required to block action potential conduction. In unstimulated tissues, the resting [3H] overflow following preincubation with [3H]-NA consisted largely of 4-hydroxy 3-methoxymandelic acid (VMA), 4-hydroxy 3-methoxy phenylglycol (MOPEG), 3,4 dihydroxyphenylglycol (DOPEG) and NA; stimulated tissues (300 pulses at 20 Hz, 0.5 ms supramaximal voltage) released mainly NA. Verapamil (0.1-1 X 10(-4) M), amlodipine (0.05-1 X 10(-4) M) and nifedipine (1-5 X 10(-4) M), but not cobalt (2 X 10(-3) M), increased, significantly, the resting overflow of 3H comprising mainly DOPEG

  4. Actions taken in response to the potential for volatile organics in RLWTF influent tanks

    SciTech Connect

    DEL SIGNORE, JOHN C.

    2007-01-01

    Positive USQD-RL W -06.0729-JPS, titled "Potential for Volatile Organics in RLW" was signed Friday, 09-08-06, at 1600. It resulted from a Potentially Inadequate Safety Analysis (PISA) for the Radioactive Liquid Waste Treatment Facility (RLWTF) at Technical Area 50. The PISA posits that an unspecified accident occurs at a generator facility, and that said accident does not ignite the volatile organic liquid, but results instead in the release of a large volume of volatile organic liquid into an RLW drain. Once in the drain, the liquid flows unimpeded into the RLWTF influent tanks. After entering the influent tanks, a spark causes a deflagration or explosion. This report documents actions taken in response to the PISA.

  5. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues

    NASA Astrophysics Data System (ADS)

    Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M.

    2016-09-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

  6. Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates.

    PubMed

    Schlaepfer, Charles H; Wessel, Ralf

    2015-01-01

    The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell's motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium's large size of around 150 µm, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students' laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around -30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20-30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature's conclusion in a V-Gated Ca(++) influx and depolarization resulting in feedback from intracellular Ca(++) that inactivates V-Gated Ca(++) channels and activates Ca-Dependent K(+) channels through a secondary messenger cascade that results in the K(+) efflux and repolarization. PMID:26557800

  7. Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials.

    PubMed

    Trantidou, Tatiana; Terracciano, Cesare M; Kontziampasis, Dimitrios; Humphrey, Eleanor J; Prodromakis, Themistoklis

    2015-01-01

    Current platforms for in vitro drug development utilize confluent, unorganized monolayers of heart cells to study the effect on action potential propagation. However, standard cell cultures are of limited use in cardiac research, as they do not preserve important structural and functional properties of the myocardium. Here we present a method to integrate a scaffolding technology with multi-electrode arrays and deliver a compact, off-the-shelf monitoring platform for growing biomimetic cardiac tissue. Our approach produces anisotropic cultures with conduction velocity (CV) profiles that closer resemble native heart tissue; the fastest impulse propagation is along the long axis of the aligned cardiomyocytes (CVL) and the slowest propagation is perpendicular (CVT), in contrast to standard cultures where action potential propagates isotropically (CVL ≈ CVT). The corresponding anisotropy velocity ratios (CVL/CVT = 1.38 - 2.22) are comparable with values for healthy adult rat ventricles (1.98 - 3.63). The main advantages of this approach are that (i) it provides ultimate pattern control, (ii) it is compatible with automated manufacturing steps and (iii) it is utilized through standard cell culturing protocols. Our platform is compatible with existing read-out equipment and comprises a prompt method for more reliable CV studies.

  8. The linear synchronization measures of uterine EMG signals: Evidence of synchronized action potentials during propagation.

    PubMed

    Domino, Malgorzata; Pawlinski, Bartosz; Gajewski, Zdzislaw

    2016-11-01

    Evaluation of synchronization between myoelectric signals can give new insights into the functioning of the complex system of porcine myometrium. We propose a model of uterine contractions according to the hypothesis of action potentials similarity which is possible to detect during propagation in the uterine wall. We introduce similarity measures based on the concept of synchronization as used in matching linear signals such as electromyographic (EMG) time series data. The aim was to present linear measures to assess synchronization between contractions in different topographic regions of the uterus. We use the cross-correlation function (ƒx,y[l], ƒy,z[l]) and the cross-coherence function (Cxy[ƒ], Cyz[ƒ]) to assess synchronization between three data series of a diestral uterine EMG bundles in porcine reproductive tract. Spontaneous uterine activity was recorded using telemetry method directly by three-channel transmitter and three silver bipolar needle electrodes sutured on different topographic regions of the reproductive tract in the sow. The results show the usefulness of the cross-coherence function in that synchronization between uterine horn and corpus uteri for multiple action potentials (bundles) could be observed. The EMG bundles synchronization may be used to investigate the direction and velocity of EMG signals propagation in porcine reproductive tract. PMID:27570104

  9. From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes.

    PubMed

    Brunet, Thibaut; Arendt, Detlev

    2016-01-01

    Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization-contraction-secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an 'emergency response' to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory-effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system.

  10. Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials

    PubMed Central

    Trantidou, Tatiana; Terracciano, Cesare M.; Kontziampasis, Dimitrios; Humphrey, Eleanor J.; Prodromakis, Themistoklis

    2015-01-01

    Current platforms for in vitro drug development utilize confluent, unorganized monolayers of heart cells to study the effect on action potential propagation. However, standard cell cultures are of limited use in cardiac research, as they do not preserve important structural and functional properties of the myocardium. Here we present a method to integrate a scaffolding technology with multi-electrode arrays and deliver a compact, off-the-shelf monitoring platform for growing biomimetic cardiac tissue. Our approach produces anisotropic cultures with conduction velocity (CV) profiles that closer resemble native heart tissue; the fastest impulse propagation is along the long axis of the aligned cardiomyocytes (CVL) and the slowest propagation is perpendicular (CVT), in contrast to standard cultures where action potential propagates isotropically (CVL ≈ CVT). The corresponding anisotropy velocity ratios (CVL/CVT = 1.38 – 2.22) are comparable with values for healthy adult rat ventricles (1.98 – 3.63). The main advantages of this approach are that (i) it provides ultimate pattern control, (ii) it is compatible with automated manufacturing steps and (iii) it is utilized through standard cell culturing protocols. Our platform is compatible with existing read-out equipment and comprises a prompt method for more reliable CV studies. PMID:26053434

  11. From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes

    PubMed Central

    Brunet, Thibaut; Arendt, Detlev

    2016-01-01

    Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization–contraction–secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an ‘emergency response’ to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory–effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system. PMID:26598726

  12. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools

    PubMed Central

    Frey, Scott H.; Povinelli, Daniel J.

    2012-01-01

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use. PMID:22106426

  13. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    PubMed

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-01

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation.

  14. Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

    PubMed Central

    Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T. Alexander

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed

  15. The Belem Framework for Action: Harnessing the Power and Potential of Adult Learning and Education for a Viable Future

    ERIC Educational Resources Information Center

    Adult Learning, 2012

    2012-01-01

    This article presents the Belem Framework for Action. This framework focuses on harnessing the power and potential of adult learning and education for a viable future. This framework begins with a preamble on adult education and towards lifelong learning.

  16. Action potential-induced dendritic calcium dynamics correlated with synaptic plasticity in developing hippocampal pyramidal cells.

    PubMed

    Isomura, Y; Kato, N

    1999-10-01

    In hippocampal CA1 pyramidal cells, intracellular calcium increases are required for induction of long-term potentiation (LTP), an activity-dependent synaptic plasticity. LTP is known to develop in magnitude during the second and third postnatal weeks in the rats. Little is known, however, about development of intracellular calcium dynamics during the same postnatal weeks. We investigated postnatal development of intracellular calcium dynamics in the proximal apical dendrites of CA1 pyramidal cells by whole cell patch-clamp recordings and calcium imaging with the Ca(2+) indicator fura-2. Dendritic calcium increases induced by intrasomatically evoked action potentials were slight during the first postnatal week but gradually became robust 3 to 6-fold during the second and third postnatal weeks. These calcium increases were blocked by application of 250 microM CdCl(2), a nonspecific blocker for high-threshold voltage-dependent calcium channels (VDCCs). Under the voltage-clamp condition, both calcium currents and dendritic calcium accumulations induced by depolarization were larger at the late developmental stage (P15-18) than the early stage (P4-7), indicating developmental enhancement of calcium influx mediated by high-threshold VDCCs. Moreover, theta-burst stimulation (TBS), a protocol for LTP induction, induced large intracellular calcium increases at the late developmental stage, in synchrony with maturation of TBS-induced LTP. These results suggest that developmental enhancement of intracellular calcium increases induced by action potentials may underlie maturation of calcium-dependent functions such as synaptic plasticity in hippocampal neurons.

  17. Calculating scattering amplitudes efficiently

    SciTech Connect

    Dixon, L.

    1996-01-01

    We review techniques for more efficient computation of perturbative scattering amplitudes in gauge theory, in particular tree and one- loop multi-parton amplitudes in QCD. We emphasize the advantages of (1) using color and helicity information to decompose amplitudes into smaller gauge-invariant pieces, and (2) exploiting the analytic properties of these pieces, namely their cuts and poles. Other useful tools include recursion relations, special gauges and supersymmetric rearrangements. 46 refs., 11 figs.

  18. A 10-form gauge potential and an M-9-brane Wess-Zumino action in massive 11D theory

    NASA Astrophysics Data System (ADS)

    Sato, T.

    2000-03-01

    We discuss some properties of an M-9-brane in ``massive 11D theory'' proposed by Bergshoeff, Lozano and Ortin. A 10-form gauge potential is consistently introduced into the massive 11D supergravity, and an M-9-brane Wess-Zumino action is constructed as that of a gauged /σ-model. Using duality relations is crucial in deriving the action, which we learn from the study of a 9-form potential in 10D massive IIA theory. A target space solution of an M-9-brane with a non-vanishing 10-form gauge field is also obtained, whose source is shown to be the M-9-brane effective action.

  19. Potential Mechanisms of Action in the Treatment of Social Impairment and Disorganization in Adolescents with ADHD

    PubMed Central

    Evans, Steven W.; Schultz, Brandon K.; Zoromski, Allison K.

    2014-01-01

    Two important domains that can be impaired in adolescents with ADHD are organization and social functioning; however, the development of interventions to target these areas in adolescents is in the early stages. Currently, small efficacy trials are beginning to be used to conduct preliminary tests on the proposed mechanisms of action for these interventions. These two studies examined the efficacy of organization and social functioning interventions for adolescents with ADHD, as well as the potential mechanisms of action for each intervention. Results from the organization intervention provide support for a significant relationship between performance on the organization checklist and overall GPA; however, there was no meaningful pattern of relationships between achieving mastery of the organization tasks and grades within quarter. Further, results from the social functioning intervention support a moderate relationship between performance on process measures of response to the intervention and outcome measures of social functioning. Results of this study provide implications for modifications to the measures and intervention procedures in future research. PMID:24748901

  20. Eudragit E100® potentiates the bactericidal action of ofloxacin against fluoroquinolone-resistant Pseudomonas aeruginosa.

    PubMed

    Romero, Verónica L; Pons, Patricia; Bocco, José L; Manzo, Rubén H; Alovero, Fabiana L

    2012-09-01

    We report the enhanced bactericidal activity of ofloxacin in drug-containing Eudragit E100(®) dispersions (EuCl-OFX) against Pseudomonas aeruginosa and the effect of the cationic polymer on bacterial membrane. Organisms treated with EuCl-OFX showed changes in cell morphology, altered outer membrane (OM) and cytoplasm with low electrodensity areas. Zeta potential of bacterial surface was shifted to positive. Sensitization to lytic agents was also observed. A profound effect on bacterial size, granularity and membrane depolarization was found by flow cytometry. Cultures exposed to drug-free polymer also showed some damaged bacterial membranes, but there was no significant cell death. Inhibition of P. aeruginosa by EuCl-OFX may involve surface effect and, to some extent, permeation effect. The cationic polymer act to mitigate the electronegativity of cell surface in the process of disorganizing the OM, rendering it more permeable to antibiotic. In addition, cytoplasmic membrane depolarization turns bacterial cell more vulnerable. The effects on membranes combined with the mechanism of action of quinolone explain the improved bactericidal action exhibited by EuCl-OFX. The behavior described for Eudragit E100(®) against P. aeruginosa may be a useful tool to broaden the spectrum of antibiotics whose clinical use is limited by the impermeability of the bacterial OM.

  1. A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty

    PubMed Central

    Dixon, David; Coates, Jonathon; del Carpio Pons, Alicia; Horabin, Joanna; Walker, Andrew; Abdul, Nicole; Kalson, Nicholas S.; Brewster, Nigel T.; Weir, David J.; Deehan, David J.; Mann, Derek A.; Borthwick, Lee A.

    2015-01-01

    Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1α/β will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL-1α/β induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infra-patellar fat pad. IL-1α/β treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1α/β availability and not their ability to respond to it. PMID:26553966

  2. Assessment of TTX-s and TTX-r Action Potential Conduction along Neurites of NGF and GDNF Cultured Porcine DRG Somata

    PubMed Central

    Jonas, Robin; Klusch, Andreas; Schmelz, Martin; Petersen, Marlen; Carr, Richard W.

    2015-01-01

    Nine isoforms of voltage-gated sodium channels (NaV) have been characterized and in excitable tissues they are responsible for the initiation and conduction of action potentials. For primary afferent neurons residing in dorsal root ganglia (DRG), individual neurons may express multiple NaV isoforms extending the neuron’s functional capabilities. Since expression of NaV isoforms can be differentially regulated by neurotrophic factors we have examined the functional consequences of exposure to either nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) on action potential conduction in outgrowing cultured porcine neurites of DRG neurons. Calcium signals were recorded using the exogenous intensity based calcium indicator Fluo-8®, AM. In 94 neurons, calcium signals were conducted along neurites in response to electrical stimulation of the soma. At an image acquisition rate of 25 Hz it was possible to discern calcium transients in response to individual electrical stimuli. The peak amplitude of electrically-evoked calcium signals was limited by the ability of the neuron to follow the stimulus frequency. The stimulus frequency required to evoke a half-maximal calcium response was approximately 3 Hz at room temperature. In 13 of 14 (93%) NGF-responsive neurites, TTX-r NaV isoforms alone were sufficient to support propagated signals. In contrast, calcium signals mediated by TTX-r NaVs were evident in only 4 of 11 (36%) neurites from somata cultured in GDNF. This establishes a basis for assessing action potential signaling using calcium imaging techniques in individual cultured neurites and suggests that, in the pig, afferent nociceptor classes relying on the functional properties of TTX-r NaV isoforms, such as cold-nociceptors, most probably derive from NGF-responsive DRG neurons. PMID:26407014

  3. Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons.

    PubMed

    Renganathan, M; Cummins, T R; Waxman, S G

    2001-08-01

    C-type dorsal root ganglion (DRG) neurons can generate tetrodotoxin-resistant (TTX-R) sodium-dependent action potentials. However, multiple sodium channels are expressed in these neurons, and the molecular identity of the TTX-R sodium channels that contribute to action potential production in these neurons has not been established. In this study, we used current-clamp recordings to compare action potential electrogenesis in Na(v)1.8 (+/+) and (-/-) small DRG neurons maintained for 2-8 h in vitro to examine the role of sodium channel Na(v)1.8 (alpha-SNS) in action potential electrogenesis. Although there was no significant difference in resting membrane potential, input resistance, current threshold, or voltage threshold in Na(v)1.8 (+/+) and (-/-) DRG neurons, there were significant differences in action potential electrogenesis. Most Na(v)1.8 (+/+) neurons generate all-or-none action potentials, whereas most of Na(v)1.8 (-/-) neurons produce smaller graded responses. The peak of the response was significantly reduced in Na(v)1.8 (-/-) neurons [31.5 +/- 2.2 (SE) mV] compared with Na(v)1.8 (+/+) neurons (55.0 +/- 4.3 mV). The maximum rise slope was 84.7 +/- 11.2 mV/ms in Na(v)1.8 (+/+) neurons, significantly faster than in Na(v)1.8 (-/-) neurons where it was 47.2 +/- 1.3 mV/ms. Calculations based on the action potential overshoot in Na(v)1.8 (+/+) and (-/-) neurons, following blockade of Ca(2+) currents, indicate that Na(v)1.8 contributes a substantial fraction (80-90%) of the inward membrane current that flows during the rising phase of the action potential. We found that fast TTX-sensitive Na(+) channels can produce all-or-none action potentials in some Na(v)1.8 (-/-) neurons but, presumably as a result of steady-state inactivation of these channels, electrogenesis in Na(v)1.8 (-/-) neurons is more sensitive to membrane depolarization than in Na(v)1.8 (+/+) neurons, and, in the absence of Na(v)1.8, is attenuated with even modest depolarization. These observations

  4. Cancer Driver Log (CanDL): Catalog of Potentially Actionable Cancer Mutations.

    PubMed

    Damodaran, Senthilkumar; Miya, Jharna; Kautto, Esko; Zhu, Eliot; Samorodnitsky, Eric; Datta, Jharna; Reeser, Julie W; Roychowdhury, Sameek

    2015-09-01

    Massively parallel sequencing technologies have enabled characterization of genomic alterations across multiple tumor types. Efforts have focused on identifying driver mutations because they represent potential targets for therapy. However, because of the presence of driver and passenger mutations, it is often challenging to assign the clinical relevance of specific mutations observed in patients. Currently, there are multiple databases and tools that provide in silico assessment for potential drivers; however, there is no comprehensive resource for mutations with functional characterization. Therefore, we created an expert-curated database of potentially actionable driver mutations for molecular pathologists to facilitate annotation of cancer genomic testing. We reviewed scientific literature to identify variants that have been functionally characterized in vitro or in vivo as driver mutations. We obtained the chromosome location and all possible nucleotide positions for each amino acid change and uploaded them to the Cancer Driver Log (CanDL) database with associated literature reference indicating functional driver evidence. In addition to a simple interface, the database allows users to download all or selected genes as a comma-separated values file for incorporation into their own analysis pipeline. Furthermore, the database includes a mechanism for third-party contributions to support updates for novel driver mutations. Overall, this freely available database will facilitate rapid annotation of cancer genomic testing in molecular pathology laboratories for mutations.

  5. Dynamics of action potential firing in electrically connected striatal fast-spiking interneurons

    PubMed Central

    Russo, Giovanni; Nieus, Thierry R.; Maggi, Silvia; Taverna, Stefano

    2013-01-01

    Fast-spiking interneurons (FSIs) play a central role in organizing the output of striatal neural circuits, yet functional interactions between these cells are still largely unknown. Here we investigated the interplay of action potential (AP) firing between electrically connected pairs of identified FSIs in mouse striatal slices. In addition to a loose coordination of firing activity mediated by membrane potential coupling, gap junctions (GJ) induced a frequency-dependent inhibition of spike discharge in coupled cells. At relatively low firing rates (2–20 Hz), some APs were tightly synchronized whereas others were inhibited. However, burst firing at intermediate frequencies (25–60 Hz) mostly induced spike inhibition, while at frequencies >50–60 Hz FSI pairs tended to synchronize. Spike silencing occurred even in the absence of GABAergic synapses or persisted after a complete block of GABAA receptors. Pharmacological suppression of presynaptic spike afterhyperpolarization (AHP) caused postsynaptic spikelets to become more prone to trigger spikes at near-threshold potentials, leading to a mostly synchronous firing activity. The complex pattern of functional coordination mediated by GJ endows FSIs with peculiar dynamic properties that may be critical in controlling striatal-dependent behavior. PMID:24294191

  6. [Adrenaline potentiates antiepileptic but not sedative action of diazepam in rats].

    PubMed

    Serdiuk, S E; Gmiro, V E

    2012-02-01

    Intramuscular (i.m.) administration ofdiazepam in a dose of 10 mg/kg and adrenaline in a dose of 0.2 mg/kg prevents generalized clonic-tonic pentylenetetrazol (PTZ) seizures in 75-80 % of rats, but only in 35-40 % of rats it prevents local clonic PTZ seizures. In the above mentioned dose, diazepam causes a strong sedation, but adrenaline does not cause a sedative effects. The combined administration of diazepam and adrenaline in threshold independently ineffective doses prevents both clonic-tonic and clonic PTZ seizures in 80 % of rats without a sedation development. The basis for mechanism of potentiation of anticonvulsant action of diazepam is the stimulation of gastric mucosa afferents by adrenaline. PMID:22650067

  7. Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action potentials.

    PubMed

    Maybeck, Vanessa; Edgington, Robert; Bongrain, Alexandre; Welch, Joseph O; Scorsone, Emanuel; Bergonzo, Philippe; Jackman, Richard B; Offenhäusser, Andreas

    2014-02-01

    The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A nonreductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators.

  8. Effect of intense sound exposure on cochlear microphonics and whole nerve action potential

    NASA Astrophysics Data System (ADS)

    Yamamura, K.; Yamamoto, N.; Kohyama, A.; Sawada, Y.; Ohno, H.; Saitoh, Y.

    1989-06-01

    An investigation was carried out to determine whether or not the critical band with Temporary Threshold Shift (TTS) is affected by exposure to high frequency sound. The function of the cochlea and the 8th nerve in guinea pigs was estimated by the intensity function and maximum output voltage of cochlear microphonics (CM) and by whole nerve action potential (Ap). Our results showed that both the intensity function and the maximum output voltage of CM and Ap decreased. Ap obtained at the test frequency higher, by half an octave, than the center frequency of the exposure noise was especially lowered. These results suggest that the critical band with TTS of both Ap and CM may be affected in exposure to high frequency sound.

  9. Action potentials occur spontaneously in squid giant axons with moderately alkaline intracellular pH.

    PubMed

    Clay, J R; Shrier, A

    2001-10-01

    This report demonstrates a novel finding from the classic giant axon preparation of the squid. Namely, the axon can be made to fire autonomously (spontaneously occurring action potentials) when the intracellular pH (pH(i)) was increased to about 7.7, or higher. (Physiological pH(i) is 7.3.) The frequency of firing was 33 Hz (T = 5 degrees ). No changes in frequency or in the voltage waveform itself were observed when pH(i) was increased from 7.7 up to 8.5. In other words, the effect has a threshold at a pH(i) of about 7.7. A mathematical model that is sufficient to mimic these results is provided using a modified version of the Clay (1998) description of the axonal ionic currents.

  10. Control and Plasticity of the Presynaptic Action Potential Waveform at Small CNS Nerve Terminals

    PubMed Central

    Hoppa, Michael B.; Gouzer, Geraldine; Armbruster, Moritz; Ryan, Timothy A.

    2014-01-01

    SUMMARY The steep dependence of exocytosis on Ca2+ entry at nerve terminals implies that voltage control of both Ca2+ channel opening and the driving force for Ca2+ entry are powerful levers in sculpting synaptic efficacy. Using fast, genetically encoded voltage indicators in dissociated primary neurons, we show that at small nerve terminals K+ channels constrain the peak voltage of the presynaptic action potential (APSYN) to values much lower than those at cell somas. This key APSYN property additionally shows adaptive plasticity: manipulations that increase presynaptic Ca2+ channel abundance and release probability result in a commensurate lowering of the APSYN peak and narrowing of the waveform, while manipulations that decrease presynaptic Ca2+ channel abundance do the opposite. This modulation is eliminated upon blockade of Kv3.1 and Kv1 channels. Our studies thus reveal that adaptive plasticity in the APSYN waveform serves as an important regulator of synaptic function. PMID:25447742

  11. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke.

    PubMed

    Li, Wentao; Xu, Haoliang; Testai, Fernando D

    2016-01-01

    Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood-brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720's mechanisms of action in stroke. PMID:27617002

  12. Effect of Cardiac Tissue Anisotropy on Three-Dimensional Electrical Action Potential Propagation

    NASA Astrophysics Data System (ADS)

    He, Zhi Zhu; Liu, Jing

    A three-dimensional (3D) electrical action potential propagation model is developed to characterize the integrated effect of cardiac tissue structure using a homogenous function with a spatial inhomogeneity. This method may be more effective for bridging the gap between computational models and experimental data for cardiac tissue anisotropy. A generalized 3D eikonal relation considering anisotropy and a self-similar evolution solution of such a relation are derived to identify the effect of anisotropy and predict the anisotropy-induced electrical wave propagation instabilities. Furthermore, the phase field equation is introduced to obtain the complex three-dimensional numerical solution of the new correlation. The present results are expected to be valuable for better understanding the physiological behavior of cardiac tissues.

  13. A supervised multi-sensor matched filter for the detection of extracellular action potentials.

    PubMed

    Szymanska, Agnieszka F; Doty, Michael; Scannell, Kathryn V; Nenadic, Zoran

    2014-01-01

    Multi-sensor extracellular recording takes advantage of several electrode channels to record from multiple neurons at the same time. However, the resulting low signal-to-noise ratio (SNR) combined with biological noise makes signal detection, the first step of any neurophysiological data analysis, difficult. A matched filter was therefore designed to better detect extracellular action potentials (EAPs) from multi-sensor extracellular recordings. The detector was tested on tetrode data from a locust antennal lobe and assessed against three trained analysts. 25 EAPs and noise samples were selected manually from the data and used for training. To reduce complexity, the filter assumed that the underlying noise in the data was spatially white. The detector performed with an average TP and FP rate of 84.62% and 16.63% respectively. This high level of performance indicates the algorithm is suitable for widespread use.

  14. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    PubMed Central

    Li, Wentao; Xu, Haoliang; Testai, Fernando D.

    2016-01-01

    Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood–brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke.

  15. Anthropomorphizing the Mouse Cardiac Action Potential via a Novel Dynamic Clamp Method

    PubMed Central

    Ahrens-Nicklas, Rebecca C.; Christini, David J.

    2009-01-01

    Abstract Interspecies differences can limit the translational value of excitable cells isolated from model organisms. It can be difficult to extrapolate from a drug- or mutation-induced phenotype in mice to human pathophysiology because mouse and human cardiac electrodynamics differ greatly. We present a hybrid computational-experimental technique, the cell-type transforming clamp, which is designed to overcome such differences by using a calculated compensatory current to convert the macroscopic electrical behavior of an isolated cell into that of a different cell type. We demonstrate the technique's utility by evaluating drug arrhythmogenicity in murine cardiomyocytes that are transformed to behave like human myocytes. Whereas we use the cell-type transforming clamp in this work to convert between mouse and human electrodynamics, the technique could be adapted to convert between the action potential morphologies of any two cell types of interest. PMID:19917221

  16. Enhanced Action Potential Passage Through the Node of Ranvier of Myelinated Axons via Proton Hopping.

    PubMed

    Kier, Lemont; Hall, Lowell; Tombes, Robert M

    2015-01-01

    Nerve impulses travel along myelinated axons as much as 300-fold faster than they do along unmyelinated axons. Myelination is essential for normal nervous system behavior in vertebrates as illustrated by leukodystrophies, such as amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS), where myelin is degenerated or damaged. The increased conduction velocity that occurs in myelinated axons is dependent on gaps in the myelin called Nodes of Ranvier that are enriched in ion channels. These Nodes are separated by long stretches of myelin insulation where no transmembrane ion conductance occurs. It is believed that the action potential jumps or skips between nodes, conserving its information content, while maintaining its speed. In this study, a model is presented that implicates Nodes of Ranvier as responsible for regenerating the proton hopping that is responsible for nerve impulse conductance in myelinated axons.

  17. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    PubMed Central

    Li, Wentao; Xu, Haoliang; Testai, Fernando D.

    2016-01-01

    Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood–brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke. PMID:27617002

  18. Effects of lead acetate on guinea pig - cochear microphonics, action potential, and motor nerve conduction velocity

    SciTech Connect

    Yamamura, K.; Maehara, N.; Terayama, K.; Ueno, N.; Kohyama, A.; Sawada, Y.; Kishi, R.

    1987-04-01

    Segmental demyelination and axonal degeneration of motor nerves induced by lead exposure is well known in man, and animals. The effect of lead acetate exposure to man may involve the cranial nerves, since vertigo and sensory neuronal deafness have been reported among lead workers. However, there are few reports concerning the dose-effects of lead acetate both to the peripheral nerve and the cranial VII nerve with measurement of blood lead concentration. The authors investigated the effects of lead acetate to the cochlea and the VIII nerve using CM (cochlear microphonics) and AP (action potential) of the guinea pigs. The effects of lead acetate to the sciatic nerve were measured by MCV of the sciatic nerve with measurement of blood lead concentration.

  19. Synapse-Level Determination of Action Potential Duration by K(+) Channel Clustering in Axons.

    PubMed

    Rowan, Matthew J M; DelCanto, Gina; Yu, Jianqing J; Kamasawa, Naomi; Christie, Jason M

    2016-07-20

    In axons, an action potential (AP) is thought to be broadcast as an unwavering binary pulse over its arbor, driving neurotransmission uniformly at release sites. Yet by recording from axons of cerebellar stellate cell (SC) interneurons, we show that AP width varies between presynaptic bouton sites, even within the same axon branch. The varicose geometry of SC boutons alone does not impose differences in spike duration. Rather, axonal patching revealed heterogeneous peak conductance densities of currents mediated mainly by fast-activating Kv3-type potassium channels, with clustered hotspots at boutons and restricted expression at adjoining shafts. Blockade of Kv channels at individual boutons indicates that currents immediately local to a release site direct spike repolarization at that location. Thus, the clustered arrangement and variable expression density of Kv3 channels at boutons are key determinants underlying compartmentalized control of AP width in a near synapse-by-synapse manner, multiplying the signaling capacity of these structures. PMID:27346528

  20. Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates

    PubMed Central

    Schlaepfer, Charles H.; Wessel, Ralf

    2015-01-01

    The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell’s motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium’s large size of around 150 µm, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students’ laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around −30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20–30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature’s conclusion in a V-Gated Ca++ influx and depolarization resulting in feedback from intracellular Ca++ that inactivates V-Gated Ca++ channels and activates Ca-Dependent K+ channels through a secondary messenger cascade that results in the K+ efflux and repolarization. PMID:26557800

  1. Mannan Oligosaccharides in Nursery Pig Nutrition and Their Potential Mode of Action

    PubMed Central

    Halas, Veronika; Nochta, Imre

    2012-01-01

    Simple Summary The aim of the paper is to provide a review of mannan oligosaccharide products in relation to their growth promoting effect and mode of action. Mannan oligosaccharide products maintain intestinal integrity and the digestive and absorptive function of the gut in the post-weaning period in pigs and enhance disease resistance by promoting antigen presentation. We find that dietary supplementation has growth promoting effects in pigs kept in a poor hygienic environment, while the positive effect of MOS is not observed in healthy pig herds with high hygienic standards. Abstract Mannan oligosaccharides (MOSs) are often referred to as one of the potential alternatives for antimicrobial growth promoters. The aim of the paper is to provide a review of mannan oligosaccharide products in relation to their growth promoting effect and mode of action based on the latest publications. We discuss the dietary impact of MOSs on (1) microbial changes, (2) morphological changes of gut tissue and digestibility of nutrients, and (3) immune response of pigs after weaning. Dietary MOSs maintain the intestinal integrity and the digestive and absorptive function of the gut in the post-weaning period. Recent results suggest that MOS enhances the disease resistance in swine by promoting antigen presentation facilitating thereby the shift from an innate to an adaptive immune response. Accordingly, dietary MOS supplementation has a potential growth promoting effect in pigs kept in a poor hygienic environment, while the positive effect of MOS is not observed in healthy pig herds with high hygienic standards that are able to maintain a high growth rate after weaning. PMID:26486920

  2. Glutamine and glutamate limit the shortening of action potential duration in anoxia-challenged rabbit hearts

    PubMed Central

    Drake, Kenneth J; Shotwell, Matthew S; Wikswo, John P; Sidorov, Veniamin Y

    2015-01-01

    In clinical conditions, amino acid supplementation is applied to improve contractile function, minimize ischemia/reperfusion injury, and facilitate postoperative recovery. It has been shown that glutamine enhances myocardial ATP/APD (action potential duration) and glutathione/oxidized glutathione ratios, and can increase hexosamine biosynthesis pathway flux, which is believed to play a role in cardioprotection. Here, we studied the effect of glutamine and glutamate on electrical activity in Langendorff-perfused rabbit hearts. The hearts were supplied by Tyrode's media with or without 2.5 mmol/L glutamine and 150 μmol/L glutamate, and exposed to two 6-min anoxias with 20-min recovery in between. Change in APD was detected using a monophasic action potential probe. A nonlinear mixed-effects regression technique was used to evaluate the effect of amino acids on APD over the experiment. Typically, the dynamic of APD change encompasses three phases: short transient increase (more prominent in the first episode), slow decrease, and fast increase (starting with the beginning of recovery). The effect of both anoxic challenge and glutamine/glutamate was cumulative, being more pronounced in the second anoxia. The amino acids' protective effect became largest by the end of anoxia – 20.0% (18.9, 95% CI: [2.6 ms, 35.1 ms]), during the first anoxia and 36.6% (27.1, 95% CI: [7.7 ms, 46.6 ms]), during the second. Following the second anoxia, APD difference between control and supplemented hearts progressively increased, attaining 10.8% (13.6, 95% CI: [4.1 ms, 23.1 ms]) at the experiments' end. Our data reveal APD stabilizing and suggest an antiarrhythmic capacity of amino acid supplementation in anoxic/ischemic conditions. PMID:26333831

  3. Correlation of repolarization of ventricular monophasic action potential with ECG in the murine heart.

    PubMed

    Danik, Stephan; Cabo, Candido; Chiello, Christine; Kang, Sacha; Wit, Andrew L; Coromilas, James

    2002-07-01

    Transgenic mice have become important experimental models in the investigation of mechanisms causing cardiac arrhythmias because of the ability to create strains with alterations in repolarizing membrane currents. It is important to relate alterations in membrane currents in cells to their phenotypic expression on the electrocardiogram (ECG). The murine ECG, however, has unusual characteristics that make interpretation of the phenotypic expression of changes in ventricular repolarization uncertain. The major deflection representing the QRS (referred to as "a") is often followed by a secondary slower deflection ("b") and sometimes a subtle third deflection ("c"). To determine whether the second or third deflections or both represent ventricular repolarization, we recorded the ventricular monophasic action potential (MAP) in open-chest mice and correlated repolarization with the ECG. There was no significant correlation by linear regression, between action potential duration to 50% or 90% repolarization (APD(50) or APD(90)), respectively, of the MAP and either the interval from onset of Q to onset of b (Qb interval) or onset of c (Qc interval). Administration of 4-aminopyridine (4-AP) significantly prolonged APD(50) and APD(90) and the Qb interval, indicating that this deflection on the ECG represents part of ventricular repolarization. After 4-AP, the c wave disappeared, also suggesting that it represents a component of ventricular repolarization. Although it appears that both the b and c waves that follow the Q wave on the ECG represent ventricular repolarization, neither correlates exactly with APD(90) of the MAP. Therefore, an accurate measurement of complete repolarization of the murine ventricle cannot be obtained from the surface ECG. PMID:12063311

  4. Acute alteration of cardiac ECG, action potential, I{sub Kr} and the human ether-a-go-go-related gene (hERG) K{sup +} channel by PCB 126 and PCB 77

    SciTech Connect

    Park, Mi-Hyeong; Park, Won Sun; Jo, Su-Hyun

    2012-07-01

    Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K{sup +} current (I{sub Kr}) of guinea pigs' hearts, and hERG K{sup +} current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD{sub 90}), and 50% of repolarization (APD{sub 50}) (P < 0.05) without changing the action potential duration at 20% (APD{sub 20}). PCB 77 decreased APD{sub 20} (P < 0.05) without affecting QTc, APD{sub 90}, and APD{sub 50}. The PCB 126 increased the I{sub Kr} in guinea-pig ventricular myocytes held at 36 °C and hERG K{sup +} current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K{sup +} current amplitude. The PCB 77 increased the diastolic Ca{sup 2+} and decreased Ca{sup 2+} transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD{sub 90} possibly by increasing I{sub Kr}, while PCB 77 decreased the APD{sub 20} possibly by other modulation related with intracellular Ca{sup 2+}. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca{sup 2+}, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K{sup +} current and I{sub Kr}. ► PCB

  5. Amplitudes of Pain-Related Evoked Potentials Are Useful to Detect Small Fiber Involvement in Painful Mixed Fiber Neuropathies in Addition to Quantitative Sensory Testing – An Electrophysiological Study

    PubMed Central

    Hansen, Niels; Kahn, Ann-Kathrin; Zeller, Daniel; Katsarava, Zaza; Sommer, Claudia; Üçeyler, Nurcan

    2015-01-01

    To investigate the usefulness of pain-related evoked potentials (PREP) elicited by electrical stimulation for the identification of small fiber involvement in patients with mixed fiber neuropathy (MFN). Eleven MFN patients with clinical signs of large fiber impairment and neuropathic pain and ten healthy controls underwent clinical and electrophysiological evaluation. Small fiber function, electrical conductivity and morphology were examined by quantitative sensory testing (QST), PREP, and skin punch biopsy. MFN was diagnosed following clinical and electrophysiological examination (chronic inflammatory demyelinating neuropathy: n = 6; vasculitic neuropathy: n = 3; chronic axonal ­neuropathy: n = 2). The majority of patients with MFN characterized their pain by descriptors that mainly represent C-fiber-mediated pain. In QST, patients displayed elevated cold, warm, mechanical, and vibration detection thresholds and cold pain thresholds indicative of MFN. PREP amplitudes in patients correlated with cold (p < 0.05) and warm detection thresholds (p < 0.05). Burning pain and the presence of par-/dysesthesias correlated negatively with PREP amplitudes (p < 0.05). PREP amplitudes correlating with cold and warm detection thresholds, burning pain, and par-/dysesthesias support employing PREP amplitudes as an additional tool in conjunction with QST for detecting small fiber impairment in patients with MFN. PMID:26696950

  6. Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity.

    PubMed

    Natarajan, A; Molnar, P; Sieverdes, K; Jamshidi, A; Hickman, J J

    2006-04-01

    The threat of environmental pollution, biological warfare agent dissemination and new diseases in recent decades has increased research into cell-based biosensors. The creation of this class of sensors could specifically aid the detection of toxic chemicals and their effects in the environment, such as pyrethroid pesticides. Pyrethroids are synthetic pesticides that have been used increasingly over the last decade to replace other pesticides like DDT. In this study we used a high-throughput method to detect pyrethroids by using multielectrode extracellular recordings from cardiac cells. The data from this cell-electrode hybrid system was compared to published results obtained with patch-clamp electrophysiology and also used as an alternative method to further understand pyrethroid effects. Our biosensor consisted of a confluent monolayer of cardiac myocytes cultured on microelectrode arrays (MEA) composed of 60 substrate-integrated electrodes. Spontaneous activity of these beating cells produced extracellular field potentials in the range of 100 microV to nearly 1200 microV with a beating frequency of 0.5-4 Hz. All of the tested pyrethroids; alpha-Cypermethrin, Tetramethrin and Tefluthrin, produced similar changes in the electrophysiological properties of the cardiac myocytes, namely reduced beating frequency and amplitude. The sensitivity of our toxin detection method was comparable to earlier patch-clamp studies, which indicates that, in specific applications, high-throughput extracellular methods can replace single-cell studies. Moreover, the similar effect of all three pyrethroids on the measured parameters suggests, that not only detection of the toxins but, their classification might also be possible with this method. Overall our results support the idea that whole cell biosensors might be viable alternatives when compared to current toxin detection methods. PMID:16198528

  7. Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

    PubMed Central

    Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

    2012-01-01

    Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

  8. A calcium-activated sodium conductance produces a long-duration action potential in the egg of a nemertean worm.

    PubMed Central

    Jaffe, L A; Kado, R T; Kline, D

    1986-01-01

    1. The egg of the nemertean worm Cerebratulus lacteus produced an action potential having a duration of about 9 min. We investigated the ionic conductances which accounted for this long-duration action potential. 2. The peak of the action potential was about +50 mV and depended on extracellular Ca2+, while the plateau potential was about +25 mV and depended on extracellular Na+. 3. Under voltage-clamp conditions, depolarization produced two temporally separate inward currents: a fast current which reached a peak at about 10 ms, and a slow current which took up to 1 min to reach its peak and lasted for several min. 4. The fast current was independent of extracellular Na+, but was blocked by removal of extracellular Ca2+. 5. The slow current was not seen when extracellular Na+ was replaced by choline+ or K+. 6. The slow current did not develop in Ca2+-free sea water, and was reduced to about half if Ca2+ was removed after the current had been initiated. 7. Microinjection of EGTA blocked the slow current, and reduced the action potential duration to about 1 min. 8. We concluded that a voltage-activated Ca2+ conductance produced the peak of the action potential, while a Ca2+-activated Na+ conductance produced its plateau. PMID:2442351

  9. Cardiac action potential duration and contractility in the intact dog heart.

    PubMed

    Drake-Holland, A J; Noble, M I; Pieterse, M; Schouten, V J; Seed, W A; ter Keurs, H E; Wohlfart, B

    1983-12-01

    The maximum rate of rise of left ventricular pressure (DP) and action potential duration (a.p.d.) were measured in closed-chest anaesthetized dogs with atrioventricular dissociation and beta-adrenergic blockade. Right ventricular stimulation was carried out with protocols consisting of a conditioning 'priming' period and a test period. When a single test stimulus was introduced at varying intervals after the priming period, DP was found to be maximal at 800-1000 ms. With this single test stimulus fixed at the optimum, DP was found to be a variable inverse function of the a.p.d. of the same beat; no positive correlation could be found between DP and a.p.d. When a second test stimulus at the optimum interval was introduced after the first, the DP (DP2) was found to be strongly dependent on that elicited by the first test stimulus (DP1); the relationship was positive, linear, independent of the method used to vary DP, and independent of whether DP1 was depressed or potentiated. The slope of the relationship was less than 1.0 and the line passed through the point where DP2 = DP1; this is the point of continuous stimulation at the optimum interval in a steady state. This result is consistent with the hypothesis that the coefficient relating DP1 to DP2, at constant a.p.d. of the first test pulse (AP1), is an index of the proportion of the activator of contraction stored during relaxation of test beat 1 which is released again on beat 2. In order to test the hypothesis that the remaining contractility depended on the action potential of test beat 1, AP1 was varied by changing the intervals between the priming stimuli. In order to determine the relationship between DP2 and AP1 it was necessary to carry out multiple regression analysis because DP2 was already known to be strongly dependent on DP1 (point 3 above), i.e. DP2 = BDP(DP1) + BAP(AP1 - D). This analysis yielded highly significant positive values for the coefficients BDP and BAP. This result is compatible with the

  10. Optimisation of Ionic Models to Fit Tissue Action Potentials: Application to 3D Atrial Modelling

    PubMed Central

    Lovell, Nigel H.; Dokos, Socrates

    2013-01-01

    A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN), intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue. PMID:23935704

  11. Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia

    PubMed Central

    Spencer, C. Ian; Baba, Shiro; Nakamura, Kenta; Hua, Ethan A.; Sears, Marie A.F.; Fu, Chi-cheng; Zhang, Jianhua; Balijepalli, Sadguna; Tomoda, Kiichiro; Hayashi, Yohei; Lizarraga, Paweena; Wojciak, Julianne; Scheinman, Melvin M.; Aalto-Setälä, Katriina; Makielski, Jonathan C.; January, Craig T.; Healy, Kevin E.; Kamp, Timothy J.; Yamanaka, Shinya; Conklin, Bruce R.

    2014-01-01

    Summary Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site. PMID:25254341

  12. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

    PubMed Central

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

    2016-01-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. PMID:27510732

  13. Evaluating the noise in electrically evoked compound action potential measurements in cochlear implants.

    PubMed

    Undurraga, Jaime A; Carlyon, Robert P; Wouters, Jan; van Wieringen, Astrid

    2012-07-01

    Electrically evoked compound action potentials (ECAPs) are widely used to study the excitability of the auditory nerve and stimulation properties in cochlear implant (CI) users. However, ECAP detection can be difficult and very subjective at near-threshold stimulation levels or in spread of excitation measurements. In this study, we evaluated the statistical properties of the background noise (BN) and the postaverage residual noise (RN) in ECAP measurements in order to determine an objective detection criterion. For the estimation of the BN and the RN, a method currently used in auditory brainstem response measurements was applied. The potential benefit of using weighted (Bayesian) averages was also examined. All estimations were performed with a set of approximately 360 ECAP measurements recorded from five human CI users of the CII or HiRes90K device (advanced bionics). Results demonstrated that the BN was normally distributed and the RN decreased according to the square root of the number of averages. No additional benefit was observed by using weighted averaging. The noise was not significantly different either at different stimulation intensities or across recording electrodes along the cochlea. The analysis of the statistical properties of the noise indicated that a signal-to-noise ratio of 1.7 dB as a detection criterion corresponds to a false positive detection rate of 1% with the used measurement setup.

  14. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials.

    PubMed

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J

    2016-01-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. PMID:27510732

  15. Human neural tuning estimated from compound action potentials in normal hearing human volunteers

    NASA Astrophysics Data System (ADS)

    Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

    2015-12-01

    The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

  16. Optophysiological Approach to Resolve Neuronal Action Potentials with High Spatial and Temporal Resolution in Cultured Neurons

    PubMed Central

    Pagès, Stéphane; Côté, Daniel; De Koninck, Paul

    2011-01-01

    Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm). Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs) have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser-scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (>10% of fluorescence change for 100 mV depolarization) and time response (sub millisecond) of the dye allows the robust detection of action potentials (APs) even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive, and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms) resolution and high spatial (μm) resolution. PMID:22016723

  17. Étude de la contribution de la diffusion simple et multiple à l'amplitude des atomes voisins du silicium dans SiO{2} : application à un granulat soumis à la réaction alcali-silice

    NASA Astrophysics Data System (ADS)

    Boinski, F.; Khouchaf, L.; Verstraete, J.; Tuilier, M. H.

    2004-11-01

    Les amplitudes des différentes distributions lointaines de la transformée de Fourier d'un spectre EXAFS contiennent des informations précieuses pour la caractérisation de l'ordre local autour d'un atome donné. Ces informations sont souvent nécessaires pour la proposition de modèles. Or souvent dans cette zone, les distances inter atomiques correspondent à des libres parcours moyens du photoélectron assez importants. La contribution due à la diffusion multiple perturbe le signal propre de la diffusion simple des atomes diffuseurs. Afin de mieux évaluer l'influence de la diffusion multiple dans nos échantillons constitués de granulats à base de SiO{2} attaqués par la réaction alcali-silice, nous avons calculé les différents parcours de diffusion simple et multiple dans ce composé. Les calculs montrent que lorsque la contribution de la diffusion multiple n'est pas atténuée, l'exploitation des voisins lointains est difficile voir impossible. La modélisation des spectres TF expérimentaux a pu être réalisée uniquement en négligeant la contribution de la diffusion multiple. Ce résultat va nous permettre l'exploitation des voisins lointains en particulier les atomes silicium dans le granulat brut et après dégradation en se basant sur le formalisme de la diffusion simple.

  18. The interactions between potassium and sodium currents in generating action potentials in the rat sympathetic neurone.

    PubMed Central

    Belluzzi, O; Sacchi, O

    1988-01-01

    V, indicating that at these membrane potentials the IA current mainly, if not exclusively, contributes to the action potential falling phase. 5. The basic features of the sympathetic neurone action potential were reconstructed by simulations based on present and previous voltage-clamp characterization of the IA, IK(V) and INa conductances.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2457694

  19. Differentiation of the action potential in the smooth muscle of canine gastric antrum using calcium-inhibitory drugs.

    PubMed

    Hohnsbein, J; Golenhofen, K

    1985-03-01

    Electrical and mechanical activity were recorded simultaneously in smooth muscle preparations from the antrum region of canine stomach by means of a single sucrose gap technique (SGT). The SGT was optimized to permit stable recording from multicellular smooth muscle preparations over several hours of electrical and mechanical activity with little disturbance of their normal properties. Acetylcholine (ACh, 10(-8) to 10(-6) M) induced or augmented dose-dependently the electrical and mechanical activity. The plateau of the action potential complex was elevated by ACh, while the contraction was increased in linear correlation to the magnitude of the plateau component. In spontaneously active (or in ACh-stimulated) preparations TEA (5 to 20 mM) magnified the plateau component, induced or strengthened spikes on the plateau ('secondary spikes'), and induced or strengthened phasic contractions. Nifedipine (10(-6) M) abolished secondary spikes, part of the plateau component of the action potential, and suppressed mechanical activity. The complex action potential of canine gastric antrum can be differentiated into (a) a basic action potential, consisting of an initial, primary spike and a plateau depolarization; this basic action potential is resistant to nifedipine and does not trigger any mechanical activity; and (b) a nifedipine-sensitive component (calcium component), which consists of an augmentation of the plateau depolarization and of secondary spikes, and which is responsible for the initiation of mechanical activity.

  20. An experimental study on the physical properties of the cupula. Effect of cupular sectioning on the ampullary nerve action potential.

    PubMed

    Suzuki, M; Harada, Y; Kishimoto, A

    1985-01-01

    The frog posterior semicircular canal (PSC) was isolated and a part of the ampullary wall was cut to allow removal of the cupula from the crista. The cupula was replaced on the crista and the PSC ampullary action potential was recorded. The cupula was again removed and was sectioned in half, either in the plane vertical to the crista (vertical sectioning), or in the plane parallel to the crista (horizontal sectioning). The sectioned half of the cupula was then replaced on the crista. The action potentials after replacement of the vertical or horizontal segments of the cupula were compared to those achieved when the entire cupula was replaced. After vertical sectioning, the action potentials were significantly reduced; they were 50.3% of the completely replaced cupula when a small stimulus was used and 79.1% when a large stimulus was used. A reduced attachment surface between the cupular base and the crista is possibly responsible for the decreased action potential in the vertically sectioned specimen. After horizontal sectioning, the action potentials were 64.5% for the small stimulus and 108.2% for the large stimulus. These results indicate that elicited responses are related to the height of the cupula and the deflection angle. This further suggests that the movement of the cupula is represented by that of the elastic system.

  1. A new method for the extraction and classification of single motor unit action potentials from surface EMG signals.

    PubMed

    Gazzoni, Marco; Farina, Dario; Merletti, Roberto

    2004-07-30

    It has been shown that multi-channel surface EMG allows assessment of anatomical and physiological single motor unit (MU) properties. To get this information, the action potentials of single MUs should be extracted from the interference EMG signals. This study describes an automatic system for the detection and classification of MU action potentials from multi-channel surface EMG signals. The methods for the identification and extraction of action potentials from the raw signals and for their clustering into the MUs to which they belong are described. The segmentation phase is based on the matched Continuous Wavelet Transform (CWT) while the classification is performed by a multi-channel neural network that is a modified version of the multi-channel Adaptive Resonance Theory networks. The neural network can adapt to slow changes in the shape of the MU action potentials. The method does not require any interaction of the operator. The technique proposed was validated on simulated signals, at different levels of force, generated by a structure based surface EMG model. The MUs identified from the simulated signals covered almost the entire recruitment curve. Thus, the proposed algorithm was able to identify a MU sample representative of the muscle. Results on experimental signals recorded from different muscles and conditions are reported, showing the possibility of investigating anatomical and physiological properties of the detected MUs in a variety of practical cases. The main limitation of the approach is that complete firing patterns can be obtained only in specific cases due to MU action potential superpositions.

  2. Novel Transabdominal Motor Action Potential (TaMAP) Neuromonitoring System for Spinal Surgery

    PubMed Central

    Feldman, Erica; Gabel, Brandon C; Taylor, Natalie; Gharib, James; Lee, Yu-Po; Taylor, William

    2016-01-01

    Introduction Minimally invasive lateral lumbar interbody fusion (LLIF) approaches to the lumbar spine reduce patient morbidity compared to anterior or posterior alternatives. This approach, however, decreases direct anatomical visualization, creating the need for highly sensitive and specific neurophysiological monitoring. We seek to determine feasibility in 'transabdominal motor action potential (TaMAP)' monitoring as an assessment for the integrity of the neural elements during lateral-approach surgeries to the lumbar spine.  Methods Cathode and anode leads were placed on the posterior and anterior surfaces of two porcine subjects. Currents of varying degrees were transmitted across, from front to back. Motor responses were monitored and recorded by needle electrodes in specific distal muscle groups of the lower extremity. Lastly, the cathode and anode were placed anterior and posterior to the chest wall and stimulated to the maximum of 1500 mA to determine any effect on cardiac rhythm. Results Responses were seen by measuring vertical height differences between peaks of corresponding evoked potentials. Recruitment began at 200 mA in the lower extremities. Stimulation at 450 mA recruited a reliable and distinguishable electrographic response from most muscle groups. Responses were recorded and reliably measured and increased in proportion to the graduation of transabdominal stimulation current; no responses were seen in the arms or face. 1500 mA across the chest wall failed to stimulate or induce cardiac arrhythmia on repeated stimulation, indicating safety of stimulation. Conclusion TaMAPs seen in the animal model provide a potential alternative to standard transcranial motor evoked potentials done in the lateral approach of LLIFs. TaMAP recordings in most muscle groups were recordable and reliable, though some muscle groups failed to stimulate. Safety of transabdominal motor evoked potentials was confirmed in this porcine study. Future studies

  3. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning.

    PubMed

    Abee, T; Krockel, L; Hill, C

    1995-12-01

    Lactic acid bacteria (LAB) play an essential role in the majority of food fermentations, and a wide variety of strains are routinely employed as starter cultures in the manufacture of dairy, meat, vegetable and bakery products. One of the most important contributions of these microorganisms is the extended shelf life of the fermented product by comparison to that of the raw substrate. Growth of spoilage and pathogenic bacteria in these foods is inhibited due to competition for nutrients and the presence of starter-derived inhibitors such as lactic acid, hydrogen peroxide and bacteriocins (Ray and Daeschel, 1992). Bacteriocins, are a heterogenous group of anti-bacterial proteins that vary in spectrum of activity, mode of action, molecular weight, genetic origin and biochemical properties. Currently, artificial chemical preservatives are employed to limit the number of microorganisms capable of growing within foods, but increasing consumer awareness of potential health risks associated with some of these substances has led researchers to examine the possibility of using bacteriocins produced by LAB as biopreservatives. The major classes of bacteriocins produced by LAB include: (I) lantibiotics, (II) small heat stable peptides, (III) large heat labile proteins, and (IV) complex proteins whose activity requires the association of carbohydrate or lipid moieties (Klaenhammer, 1993). Significantly however, the inhibitory activity of these substances is confined to Gram-positive bacteria and inhibition of Gram-negatives by these bacteriocins has not been demonstrated, an observation which can be explained by a detailed analysis and comparison of the composition of Gram-positive and Gram-negative bacterial cell walls (Fig. 1). In both types the cytoplasmic membrane which forms the border between the cytoplasm and the external environment, is surrounded by a layer of peptidoglycan which is significantly thinner in Gram-negative bacteria than in Gram-positive bacteria. Gram

  4. PULSE AMPLITUDE ANALYZER

    DOEpatents

    Greenblatt, M.H.

    1958-03-25

    This patent pertains to pulse amplitude analyzers for sorting and counting a serles of pulses, and specifically discloses an analyzer which ls simple in construction and presents the puise height distribution visually on an oscilloscope screen. According to the invention, the pulses are applied to the vertical deflection plates of an oscilloscope and trigger the horizontal sweep. Each pulse starts at the same point on the screen and has a maximum amplitude substantially along the same vertical line. A mask is placed over the screen except for a slot running along the line where the maximum amplitudes of the pulses appear. After the slot has been scanned by a photocell in combination with a slotted rotating disk, the photocell signal is displayed on an auxiliary oscilloscope as vertical deflection along a horizontal time base to portray the pulse amplitude distribution.

  5. PULSE AMPLITUDE ANALYSERS

    DOEpatents

    Lewis, I.A.D.

    1956-05-15

    This patent pentains to an electrical pulse amplitude analyzer, capable of accepting input pulses having a separation between adjacent pulses in the order of one microsecond while providing a large number of channels of classification. In its broad aspect the described pulse amplitude analyzer utilizes a storage cathode ray tube und control circuitry whereby the amplitude of the analyzed pulses controls both the intensity and vertical defiection of the beam to charge particular spots in horizontal sectors of the tube face as the beam is moved horizontally across the tube face. As soon as the beam has swept the length of the tube the information stored therein is read out by scanning individually each horizontal sector corresponding to a certain range of pulse amplitudes and applying the output signal from each scan to separate indicating means.

  6. Mechano-perception in Chara cells: the influence of salinity and calcium on touch-activated receptor potentials, action potentials and ion transport.

    PubMed

    Shepherd, Virginia A; Beilby, Mary J; Al Khazaaly, Sabah A S; Shimmen, Teruo

    2008-11-01

    This paper investigates the impact of increased salinity on touch-induced receptor and action potentials of Chara internodal cells. We resolved underlying changes in ion transport by current/voltage analysis. In a saline medium with a low Ca(2+) ion concentration [(Ca(2+))(ext)], the cell background conductance significantly increased and proton pump currents declined to negligible levels, depolarizing the membrane potential difference (PD) to the excitation threshold [action potential (AP)(threshold)]. The onset of spontaneous repetitive action potentials further depolarized the PD, activating K(+) outward rectifying (KOR) channels. K(+) efflux was then sustained and irrevocable, and cells were desensitized to touch. However, when [Ca(2+)](ext) was high, the background conductance increased to a lesser extent and proton pump currents were stimulated, establishing a PD narrowly negative to AP(threshold). Cells did not spontaneously fire, but became hypersensitive to touch. Even slight touch stimulus induced an action potential and further repetitive firing. The duration of each excitation was extended when [Ca(2+)](ext) was low. Cell viability was prolonged in the absence of touch stimulus. Chara cells eventually depolarize and die in the saline media, but touch-stimulated and spontaneous excitation accelerates the process in a Ca(2+)-dependent manner. Our results have broad implications for understanding the interactions between mechano-perception and salinity stress in plants.

  7. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials.

    PubMed

    Shtrahman, Matthew; Aharoni, Daniel B; Hardy, Nicholas F; Buonomano, Dean V; Arisaka, Katsushi; Otis, Thomas S

    2015-02-01

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations.

  8. Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light

    PubMed Central

    Schei, Jennifer L.; McCluskey, Matthew D.; Foust, Amanda J.; Yao, Xin-Cheng; Rector, David M.

    2008-01-01

    To identify the neural constituents responsible for generating polarized light changes, we created spatially resolved movies of propagating action potentials from stimulated lobster leg nerves using both reflection and transmission imaging modalities. Changes in light polarization are associated with membrane depolarization and provide sub-millisecond temporal resolution. Typically, signals are detected using light transmitted through tissue; however, because we eventually would like to apply polarization techniques in-vivo, reflected light is required. In transmission mode, the optical signal was largest throughout the center of the nerve, suggesting that most of the optical signal arose from the inner nerve bundle. In reflection mode, polarization changes were largest near the edges, suggesting that most of the optical signal arose from the outer sheath. In support of these observations, an optical model of the tissue showed that the outer sheath is more reflective while the inner nerve bundle is more transmissive. In order to apply these techniques in-vivo, we must consider that brain tissue does not have a regular orientation of processes as in the lobster nerve. We tested the effect of randomizing cell orientation by tying the nerve in an overhand knot prior to imaging, producing polarization changes that can be imaged even without regular cell orientations. PMID:18272402

  9. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

    PubMed Central

    Hiester, Brian G.; Jones, Kevin R.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates both action potential (AP) generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function. PMID:27683544

  10. A new three-variable mathematical model of action potential propagation in cardiac tissue.

    NASA Astrophysics Data System (ADS)

    Fenton, Flavio; Karma, Alain

    1996-03-01

    Modeling the electrical activity of the heart, and the complex signaling patterns which underly dangerous arrhythmias such as tachycardia and fibrillation, requires a quantitative model of action potential (AP) propagation. At present, there exist detailed ionic models of the Hodgkin-Huxley form that accurately reproduce dynamical features of the AP at a single cell level (e.g. Luo-Rudy, 1994). However, such models are not computationally tractable to study propagation in two and three-dimensional tissues of many resistively coupled cells. At the other extreme, there exists generic models of excitable media, such as the well-known FitzHugh-Nagumo model, which are only qualitative and do not reproduce essential dynamical features of cardiac AP. A new three-variable model is introduced which bridges the gap between these two types of models. It reproduces quantitatively important `mesoscopic' dynamical properties which are specific to cardiac AP, namely restitution and dispersion. At the same time, it remains computationally tractable and makes it possible to study the effect of these properties on the initiation, dynamics, and stability of complex reentrant excitations in two and three dimensions. Preliminary numerical results of the effect of restitution and dispersion on two-dimensional reentry (i.e. spiral waves) are presented.

  11. Action Potential Energy Efficiency Varies Among Neuron Types in Vertebrates and Invertebrates

    PubMed Central

    Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B.; Niven, Jeremy E.

    2010-01-01

    The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na+ and K+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin–Huxley model of the squid axon, optimizing the kinetics or number of Na+ and K+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost. PMID:20617202

  12. Action potential-like’ ST elevation following pseudo-Wellens' electrocardiogram

    PubMed Central

    Oksuz, Fatih; Sensoy, Baris; Sen, Fatih; Celik, Ethem; Ozeke, Ozcan; Maden, Orhan

    2015-01-01

    Coronary artery vasospasm is an important cause of chest pain syndromes that can lead to myocardial infarction, ventricular arrhythmias, and sudden death. In 1959, Prinzmetal et al described a syndrome of nonexertional chest pain with ST-segment elevation on electrocardiography. Persistent angina is challenging, and repeated coronary angioplasty may be required in this syndrome. Calcium antagonists are extremely effective in treating and preventing coronary spasm, and may provide long-lasting relief for the patient. Whereas the Wellens' syndrome is characterized by symmetrically inverted T-waves with preserved R waves in the precordial leads suggestive of impending myocardial infarction due to a critical proximal left anterior descending stenosis, the pseudo-Wellens' syndrome caused by coronary artery spasm has also rarely been reported in literature. We present a pseudo-Wellens syndrome as a cause of vasospastic angina, and a diffuse ST segment elavation on electrocardiogram resembling the Greek letter lambda, called also 'action potential-like' ECG in a patient with vasospastic-type Printzmetal angina. PMID:26432739

  13. Efficacy of action potential simulation and interferential therapy in the rehabilitation of patients with knee osteoarthritis

    PubMed Central

    Eftekharsadat, Bina; Habibzadeh, Afshin; Kolahi, Babak

    2015-01-01

    Objective: Knee osteoarthritis (OA) is the main cause of pain, physical impairment and chronic disability in older people. Electrotherapeutic modalities such as interferential therapy (IFT) and action potential simulation (APS) are used for the treatment of knee OA. In this study, we aim to evaluate the therapeutic effects of APS and IFT on knee OA. Methods: In this randomized clinical trial, 67 patients (94% female and 6% male with mean age of 52.80 ± 8.16 years) with mild and moderate knee OA were randomly assigned to be treated with APS (n = 34) or IFT (n = 33) for 10 sessions in 4 weeks. Baseline and post-treatment Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscales, visual analogue scale (VAS) and timed up and go (TUG) test were measured in all patients. Results: VAS and WOMAC subscales were significantly improved after treatment in APS and IFT groups (p < 0.001 for all). TUG was also significantly improved after treatment in APS group (p < 0.001), but TUG changes in IFT was not significant (p = 0.09). There was no significant difference in VAS, TUG and WOMAC subscales values before and after treatment as well as the mean improvement in VAS, TUG and WOMAC subscales during study between groups. Conclusion: Short-term treatment with both APS and IFT could significantly reduce pain and improve physical function in patients with knee OA. PMID:26029268

  14. Wavelet Transform for Real-Time Detection of Action Potentials in Neural Signals

    PubMed Central

    Quotb, Adam; Bornat, Yannick; Renaud, Sylvie

    2011-01-01

    We present a study on wavelet detection methods of neuronal action potentials (APs). Our final goal is to implement the selected algorithms on custom integrated electronics for on-line processing of neural signals; therefore we take real-time computing as a hard specification and silicon area as a price to pay. Using simulated neural signals including APs, we characterize an efficient wavelet method for AP extraction by evaluating its detection rate and its implementation cost. We compare software implementation for three methods: adaptive threshold, discrete wavelet transform (DWT), and stationary wavelet transform (SWT). We evaluate detection rate and implementation cost for detection functions dynamically comparing a signal with an adaptive threshold proportional to its SD, where the signal is the raw neural signal, respectively: (i) non-processed; (ii) processed by a DWT; (iii) processed by a SWT. We also use different mother wavelets and test different data formats to set an optimal compromise between accuracy and silicon cost. Detection accuracy is evaluated together with false negative and false positive detections. Simulation results show that for on-line AP detection implemented on a configurable digital integrated circuit, APs underneath the noise level can be detected using SWT with a well-selected mother wavelet, combined to an adaptive threshold. PMID:21811455

  15. Wavelet transform for real-time detection of action potentials in neural signals.

    PubMed

    Quotb, Adam; Bornat, Yannick; Renaud, Sylvie

    2011-01-01

    We present a study on wavelet detection methods of neuronal action potentials (APs). Our final goal is to implement the selected algorithms on custom integrated electronics for on-line processing of neural signals; therefore we take real-time computing as a hard specification and silicon area as a price to pay. Using simulated neural signals including APs, we characterize an efficient wavelet method for AP extraction by evaluating its detection rate and its implementation cost. We compare software implementation for three methods: adaptive threshold, discrete wavelet transform (DWT), and stationary wavelet transform (SWT). We evaluate detection rate and implementation cost for detection functions dynamically comparing a signal with an adaptive threshold proportional to its SD, where the signal is the raw neural signal, respectively: (i) non-processed; (ii) processed by a DWT; (iii) processed by a SWT. We also use different mother wavelets and test different data formats to set an optimal compromise between accuracy and silicon cost. Detection accuracy is evaluated together with false negative and false positive detections. Simulation results show that for on-line AP detection implemented on a configurable digital integrated circuit, APs underneath the noise level can be detected using SWT with a well-selected mother wavelet, combined to an adaptive threshold.

  16. Action potential duration dispersion and alternans in simulated heterogeneous cardiac tissue with a structural barrier.

    PubMed

    Krogh-Madsen, Trine; Christini, David J

    2007-02-15

    Structural barriers to wave propagation in cardiac tissue are associated with a decreased threshold for repolarization alternans both experimentally and clinically. Using computer simulations, we investigated the effects of a structural barrier on the onset of spatially concordant and discordant alternans. We used two-dimensional tissue geometry with heterogeneity in selected potassium conductances to mimic known apex-base gradients. Although we found that the actual onset of alternans was similar with and without the structural barrier, the increase in alternans magnitude with faster pacing was steeper with the barrier--giving the appearance of an earlier alternans onset in its presence. This is consistent with both experimental structural barrier findings and the clinical observation of T-wave alternans occurring at slower pacing rates in patients with structural heart disease. In ionically homogeneous tissue, discordant alternans induced by the presence of the structural barrier arose at intermediate pacing rates due to a source-sink mismatch behind the barrier. In heterogeneous tissue, discordant alternans occurred during fast pacing due to a barrier-induced decoupling of tissue with different restitution properties. Our results demonstrate a causal relationship between the presence of a structural barrier and increased alternans magnitude and action potential duration dispersion, which may contribute to why patients with structural heart disease are at higher risk for ventricular tachyarrhythmias.

  17. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation.

    PubMed

    Galati, Domenico F; Hiester, Brian G; Jones, Kevin R

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates both action potential (AP) generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF's effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF's function. PMID:27683544

  18. Modeling back propagating action potential in weakly excitable dendrites of neocortical pyramidal cells.

    PubMed Central

    Rapp, M; Yarom, Y; Segev, I

    1996-01-01

    Simultaneous recordings from the soma and apical dendrite of layer V neocortical pyramidal cells of young rats show that, for any location of current input, an evoked action potential (AP) always starts at the axon and then propagates actively, but decrementally, backward into the dendrites. This back-propagating AP is supported by a low density (-gNa = approximately 4 mS/cm2) of rapidly inactivating voltage-dependent Na+ channels in the soma and the apical dendrite. Investigation of detailed, biophysically constrained, models of reconstructed pyramidal cells shows the following. (i) The initiation of the AP first in the axon cannot be explained solely by morphological considerations; the axon must be more excitable than the soma and dendrites. (ii) The minimal Na+ channel density in the axon that fully accounts for the experimental results is about 20-times that of the soma. If -gNa in the axon hillock and initial segment is the same as in the soma [as recently suggested by Colbert and Johnston [Colbert, C. M. & Johnston, D. (1995) Soc. Neurosci. Abstr. 21, 684.2

  19. Modeling back propagating action potential in weakly excitable dendrites of neocortical pyramidal cells.

    PubMed

    Rapp, M; Yarom, Y; Segev, I

    1996-10-15

    Simultaneous recordings from the soma and apical dendrite of layer V neocortical pyramidal cells of young rats show that, for any location of current input, an evoked action potential (AP) always starts at the axon and then propagates actively, but decrementally, backward into the dendrites. This back-propagating AP is supported by a low density (-gNa = approximately 4 mS/cm2) of rapidly inactivating voltage-dependent Na+ channels in the soma and the apical dendrite. Investigation of detailed, biophysically constrained, models of reconstructed pyramidal cells shows the following. (i) The initiation of the AP first in the axon cannot be explained solely by morphological considerations; the axon must be more excitable than the soma and dendrites. (ii) The minimal Na+ channel density in the axon that fully accounts for the experimental results is about 20-times that of the soma. If -gNa in the axon hillock and initial segment is the same as in the soma [as recently suggested by Colbert and Johnston [Colbert, C. M. & Johnston, D. (1995) Soc. Neurosci. Abstr. 21, 684.2

  20. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials.

    PubMed

    Shtrahman, Matthew; Aharoni, Daniel B; Hardy, Nicholas F; Buonomano, Dean V; Arisaka, Katsushi; Otis, Thomas S

    2015-02-01

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. PMID:25650920

  1. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

    PubMed Central

    Hiester, Brian G.; Jones, Kevin R.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates both action potential (AP) generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function.

  2. Frequency decoding of periodically timed action potentials through distinct activity patterns in a random neural network

    NASA Astrophysics Data System (ADS)

    Reichenbach, Tobias; Hudspeth, A. J.

    2012-11-01

    Frequency discrimination is a fundamental task of the auditory system. The mammalian inner ear, or cochlea, provides a place code in which different frequencies are detected at different spatial locations. However, a temporal code based on spike timing is also available: action potentials evoked in an auditory-nerve fiber by a low-frequency tone occur at a preferred phase of the stimulus—they exhibit phase locking—and thus provide temporal information about the tone's frequency. Humans employ this temporal information for discrimination of low frequencies. How might such temporal information be read out in the brain? Here we employ statistical and numerical methods to demonstrate that recurrent random neural networks in which connections between neurons introduce characteristic time delays, and in which neurons require temporally coinciding inputs for spike initiation, can perform sharp frequency discrimination when stimulated with phase-locked inputs. Although the frequency resolution achieved by such networks is limited by the noise in phase locking, the resolution for realistic values reaches the tiny frequency difference of 0.2% that has been measured in humans.

  3. Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.

    PubMed

    Fabbro, Alessandra; Sucapane, Antonietta; Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies.

  4. Latencies in action potential stimulation in a two-dimensional bidomain: A numerical simulation

    NASA Astrophysics Data System (ADS)

    Barach, John Paul

    1991-05-01

    A numerical simulation is performed in which a uniform planar slab of idealized cardiac tissue is stimulated at the center. The cardiac slab is modeled as an anisotropic bidomain; within each domain current flow is determined by a forced diffusion equation in which the transmembrane current connecting the domains provides the forcing term. An action potential (AP) propagates outward after a time latency dependent upon the stimulus size and the physiological variables. Its isochrones are elliptical with an asymmetry that is a small fraction of the imposed asymmetry in resistivity. External voltages resemble the first derivative of those in the internal domain and tests with continuing stimuli exhibit a relaxation time of about 3 ms and space constants that agree with other work. The AP latency increases very strongly near threshold stimulus and decreases as the log (stimulus) for large stimuli in the ``virtual cathode'' range. Latencies in the longitudinal, transverse, and diagonal directions are found to be the same over a wide range of stimulus size and type.

  5. Improved health and growth of fish fed mannan oligosaccharides: potential mode of action.

    PubMed

    Torrecillas, Silvia; Montero, Daniel; Izquierdo, Marisol

    2014-02-01

    Nowadays, aquaculture industry still confronts several disease-related problems mainly caused by viruses, bacteria and parasites. In the last decade, the use of mannan oligosaccharides (MOS) in fish production has received increased attention due to its beneficial effects on fish performance and disease resistance. This review shows the MOS use in aquaculture with a specific emphasis on the effectiveness of the several MOS forms available in the market related to disease resistance, fish nutrition and the possible mechanisms involved. Among the main beneficial effects attributed to MOS dietary supplementation, enhanced fish performance, feed efficiency and pathogen protection by potentiation of the systemic and local immune system and the reinforcement of the epithelial barrier structure and functionality are some of the most commonly demonstrated benefits. These combined effects suggest that the reinforcement of the intestinal integrity and functionality, together with the stimulation of the innate immune system, are the primary mode of action of MOS in fish. However, the supplementation strategy related to the structure of the MOS added, the correct dose and duration, as well as fish species, size and culture conditions are determinant factors to achieve improvements in health status and growth performance.

  6. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders.

    PubMed

    Chiu, Chi-Tso; Chuang, De-Maw

    2010-11-01

    Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium's therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurotrophic properties against various insults, and considerable clinical potential for the treatment of several neurodegenerative conditions. Evidence from pharmacological and gene manipulation studies support the notion that glycogen synthase kinase-3 inhibition and induction of brain-derived neurotrophic factor-mediated signaling are lithium's main mechanisms of action, leading to enhanced cell survival pathways and alteration of a wide variety of downstream effectors. By inhibiting N-methyl-D-aspartate receptor-mediated calcium influx, lithium also contributes to calcium homeostasis and suppresses calcium-dependent activation of pro-apoptotic signaling pathways. In addition, lithium decreases inositol 1,4,5-trisphosphate by inhibiting phosphoinositol phosphatases, a process recently identified as a novel mechanism for inducing autophagy. Through these mechanisms, therapeutic doses of lithium have been demonstrated to defend neuronal cells against diverse forms of death insults and to improve behavioral as well as cognitive deficits in various animal models of neurodegenerative diseases, including stroke, amyotrophic lateral sclerosis, fragile X syndrome, as well as Huntington's, Alzheimer's, and Parkinson's diseases, among others. Several clinical trials are also underway to assess the therapeutic effects of lithium for treating these disorders. This article reviews the most recent findings regarding the potential targets involved in lithium's neuroprotective effects, and the implication of these findings for the treatment of a variety of diseases.

  7. Ionic mechanisms maintaining action potential conduction velocity at high firing frequencies in an unmyelinated axon.

    PubMed

    Cross, Kevin P; Robertson, R Meldrum

    2016-05-01

    The descending contralateral movement detector (DCMD) is a high-performance interneuron in locusts with an axon capable of transmitting action potentials (AP) at more than 500 Hz. We investigated biophysical mechanisms for fidelity of high-frequency transmission in this axon. We measured conduction velocities (CVs) at room temperature during exposure to 10 mmol/L cadmium, a calcium current antagonist, and found significant reduction in CV with reduction at frequencies >200 Hz of ~10%. Higher temperatures induced greater CV reductions during exposure to cadmium across all frequencies of ~20-30%. Intracellular recordings during 15 min of exposure to cadmium or nickel, also a calcium current antagonist, revealed an increase in the magnitude of the afterhyperpolarization potential (AHP) and the time to recover to baseline after the AHP (Medians for Control: -19.8%; Nickel: 167.2%; Cadmium: 387.2%), that could be due to a T-type calcium current. However, the removal of extracellular calcium did not mimic divalent cation exposure suggesting calcium currents are not the cause of the AHP increase. Computational modeling showed that the effects of the divalent cations could be modeled with a persistent sodium current which could be blocked by high concentrations of divalent cations. Persistent sodium current shortened the AHP duration in our models and increased CV for high-frequency APs. We suggest that faithful, high-frequency axonal conduction in the DCMD is enabled by a mechanism that shortens the AHP duration like a persistent or resurgent sodium current. PMID:27225630

  8. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake.

    PubMed

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A S; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-02-01

    Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant. PMID:26804557

  9. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

    PubMed Central

    Chiu, Chi-Tso; Chuang, De-Maw

    2011-01-01

    Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium’s therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurotrophic properties against various insults, and considerable clinical potential for the treatment of several neurodegenerative conditions. Evidence from pharmacological and gene manipulation studies support the notion that glycogen synthase kinase-3 inhibition and induction of brain-derived neurotrophic factor-mediated signaling are lithium’s main mechanisms of action, leading to enhanced cell survival pathways and alteration of a wide variety of downstream effectors. By inhibiting N-methyl-D-aspartate receptor-mediated calcium influx, lithium also contributes to calcium homeostasis and suppresses calcium-dependent activation of pro-apoptotic signaling pathways. In addition, lithium decreases inositol 1,4,5-trisphosphate by inhibiting phosphoinositol phosphatases, a process recently identified as a novel mechanism for inducing autophagy. Through these mechanisms, therapeutic doses of lithium have been demonstrated to defend neuronal cells against diverse forms of death insults and to improve behavioral as well as cognitive deficits in various animal models of neurodegenerative diseases, including stroke, amyotrophic lateral sclerosis, fragile X syndrome, as well as Huntington’s, Alzheimer’s, and Parkinson’s diseases, among others. Several clinical trials are also underway to assess the therapeutic effects of lithium for treating these disorders. This article reviews the most recent findings regarding the potential targets involved in lithium’s neuroprotective effects, and the implication of these findings for the treatment of a variety of diseases. PMID:20705090

  10. Antifungal potential of Sideroxylon obtusifolium and Syzygium cumini and their mode of action against Candida albicans.

    PubMed

    Pereira, Jozinete Vieira; Freires, Irlan Almeida; Castilho, Aline Rogéria; da Cunha, Marcos Guilherme; Alves, Harley da Silva; Rosalen, Pedro Luiz

    2016-10-01

    Context The emergence of resistant pathogens and toxicity of antifungals have encouraged an active search for novel candidates to manage Candida biofilms. Objective In this study, the little known species Sideroxylon obtusifolium T.D. Penn (Sapotacea) and Syzygium cumini (L.) Skeels (Myrtaceae), from the Caatinga biome in Brazil were chemically characterized and explored for their antifungal potential against C. albicans. Materials and methods We determined the effects of hydroalcoholic extracts/fractions upon fungal growth (minimum inhibitory and fungicidal concentrations, MIC/MFC), biofilm morphology (scanning electron microscopy) and viability (confocal laser scanning microscopy), proposed their mode of action (sorbitol and ergosterol assays), and finally investigated their effects against macrophage and keratinocyte cells in a cell-based assay. Data were analysed using one-way analysis of variance with Tukey-Kramer post-test (α = 0.05). Results The n-butanol (Nb) fraction from S. obtusifolium and S. cumini extract (Sc) showed flavonoids (39.11 ± 6.62 mg/g) and saponins (820.35 ± 225.38 mg/g), respectively, in their chemical composition and demonstrated antifungal activity, with MICs of 62.5 and 125 μg/mL, respectively. Nb and Sc may complex with ergosterol as there was a 4-16-fold increase in MICs in the presence of exogenous ergosterol, leading to disrupted permeability of cell membrane. Deleterious effects were observed on morphology and viability of treated biofilms from concentrations as low as their MICs and higher. Sc was not toxic to macrophages and keratinocytes at these concentrations (p > 0.05), unlike Nb. Conclusions Nb and Sc demonstrated considerable antifungal activity and should be further investigated as potential alternative candidates to treat Candida biofilms. PMID:26987037

  11. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake

    PubMed Central

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D.; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A.S.; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-01-01

    Summary Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na+-rich animal and nutrition for the plant. Video Abstract PMID:26804557

  12. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics.

    PubMed

    Kapucu, Fikret E; Tanskanen, Jarno M A; Mikkonen, Jarno E; Ylä-Outinen, Laura; Narkilahti, Susanna; Hyttinen, Jari A K

    2012-01-01

    In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESCs), exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI) histograms. Moreover, the algorithm calculates ISI thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average (CMA) and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA) data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  13. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake.

    PubMed

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A S; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-02-01

    Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant.

  14. Action potential waveform voltage clamp shows significance of different Ca2+ channel types in developing ascidian muscle

    PubMed Central

    Dallman, Julia E; Dorman, Jennie B; Moody, William J

    2000-01-01

    Early in development, ascidian muscle cells generate spontaneous, long-duration action potentials that are mediated by a high-threshold, inactivating Ca2+ current. This spontaneous activity is required for appropriate physiological development.Mature muscle cells generate brief action potentials only in response to motor neuron input. The mature action potential is mediated by a high-threshold sustained Ca2+ current.Action potentials recorded from these two stages were imposed as voltage-clamp commands on cells of the same and different stages from which they were recorded. This strategy allowed us to study how immature and mature Ca2+ currents are optimized to their particular functions.Total Ca2+ entry during an action potential did not change during development. The developmental increase in Ca2+ current density exactly compensated for decreased spike duration. This compensation was a function purely of Ca2+ current density, not of the transition from immature to mature Ca2+ current types.In immature cells, Ca2+ entry was spread out over the entire waveform of spontaneous activity, including the interspike voltage trajectory. This almost continuous Ca2+ entry may be important in triggering Ca2+-dependent developmental programmes, and is a function of the slightly more negative voltage dependence of the immature Ca2+ current.In contrast, Ca2+ entry in mature cells was confined to the action potential itself, because of the slightly more positive voltage dependence of the mature Ca2+ current. This may be important in permitting rapid contraction-relaxation cycles during larval swimming.The inactivation of the immature Ca2+ current serves to limit the frequency and burst duration of spontaneous activity. The sustained kinetics of the mature Ca2+ current permit high-frequency firing during larval swimming. PMID:10766919

  15. Small amplitude quasibreathers and oscillons

    NASA Astrophysics Data System (ADS)

    Fodor, Gyula; Forgács, Péter; Horváth, Zalán; Lukács, Árpád

    2008-07-01

    Quasibreathers (QB) are time-periodic solutions with weak spatial localization introduced in G. Fodor et al. in [Phys. Rev. D 74, 124003 (2006)PRVDAQ0556-282110.1103/PhysRevD.74.124003]. QB’s provide a simple description of oscillons (very long-living spatially localized time dependent solutions). The small amplitude limit of QB’s is worked out in a large class of scalar theories with a general self-interaction potential, in D spatial dimensions. It is shown that the problem of small amplitude QB’s is reduced to a universal elliptic partial differential equation. It is also found that there is the critical dimension, Dcrit=4, above which no small amplitude QB’s exist. The QB’s obtained this way are shown to provide very good initial data for oscillons. Thus these QB’s provide the solution of the complicated, nonlinear time dependent problem of small amplitude oscillons in scalar theories.

  16. A simple circuit for producing vertical arrays of analogue signals and dot raster displays of nerve and muscle action potentials.

    PubMed

    Miles, T S; Woodland, M J

    1986-03-01

    It is often helpful to display analogue signals such as electromyograms, electroencephalograms, nerve action potentials, etc., in a regular vertical array. A special case of this display is the widely-used dot raster. This paper describes a simple circuit which enables up to 31 analogue signals to be thus displayed on an analogue storage oscilloscope screen or X-Y plotter. A modification permits up to 255 trials to be displayed. The same circuit produces a standard, dot raster display from standard pulses representing nerve or muscle cell action potentials.

  17. Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

    2011-11-01

    The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

  18. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    USGS Publications Warehouse

    Elskus, Adria A.

    2012-01-01

    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to

  19. Facilitating Youth to Take Sustainability Actions: The Potential of Peer Education

    ERIC Educational Resources Information Center

    de Vreede, Catherine; Warner, Alan; Pitter, Robert

    2014-01-01

    Peer education is an understudied yet valuable strategy for sustainability educators in shifting youth to take action for sustainability. This case study conceptualizes the change process in facilitating youth to take sustainability actions, and explores the benefits, dynamics, and challenges of peer education as a strategy in facilitating change.…

  20. Encoding of point of view during action observation in the local field potentials of macaque area F5.

    PubMed

    Caggiano, Vittorio; Giese, Martin; Thier, Peter; Casile, Antonino

    2015-02-01

    The discovery of mirror neurons compellingly shows that the monkey premotor area F5 is active not only during the execution but also during the observation of goal-directed motor acts. Previous studies have addressed the functioning of the mirror-neuron system at the single-unit level. Here, we tackled this research question at the network level by analysing local field potentials in area F5 while the monkey was presented with goal-directed actions executed by a human or monkey actor and observed either from a first-person or third-person perspective. Our analysis showed that rhythmic responses are not only present in area F5 during action observation, but are also modulated by the point of view. Observing an action from a subjective point of view produced significantly higher power in the low-frequency band (2-10 Hz) than observing the same action from a frontal view. Interestingly, an increase in power in the 2-10 Hz band was also produced by the execution of goal-directed motor acts. Independently of the point of view, action observation also produced a significant decrease in power in the 15-40 Hz band and an increase in the 60-100 Hz band. These results suggest that, depending on the point of view, action observation might activate different processes in area F5. Furthermore, they may provide information about the functional architecture of action perception in primates.

  1. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning.

    PubMed

    Abee, T; Krockel, L; Hill, C

    1995-12-01

    Lactic acid bacteria (LAB) play an essential role in the majority of food fermentations, and a wide variety of strains are routinely employed as starter cultures in the manufacture of dairy, meat, vegetable and bakery products. One of the most important contributions of these microorganisms is the extended shelf life of the fermented product by comparison to that of the raw substrate. Growth of spoilage and pathogenic bacteria in these foods is inhibited due to competition for nutrients and the presence of starter-derived inhibitors such as lactic acid, hydrogen peroxide and bacteriocins (Ray and Daeschel, 1992). Bacteriocins, are a heterogenous group of anti-bacterial proteins that vary in spectrum of activity, mode of action, molecular weight, genetic origin and biochemical properties. Currently, artificial chemical preservatives are employed to limit the number of microorganisms capable of growing within foods, but increasing consumer awareness of potential health risks associated with some of these substances has led researchers to examine the possibility of using bacteriocins produced by LAB as biopreservatives. The major classes of bacteriocins produced by LAB include: (I) lantibiotics, (II) small heat stable peptides, (III) large heat labile proteins, and (IV) complex proteins whose activity requires the association of carbohydrate or lipid moieties (Klaenhammer, 1993). Significantly however, the inhibitory activity of these substances is confined to Gram-positive bacteria and inhibition of Gram-negatives by these bacteriocins has not been demonstrated, an observation which can be explained by a detailed analysis and comparison of the composition of Gram-positive and Gram-negative bacterial cell walls (Fig. 1). In both types the cytoplasmic membrane which forms the border between the cytoplasm and the external environment, is surrounded by a layer of peptidoglycan which is significantly thinner in Gram-negative bacteria than in Gram-positive bacteria. Gram

  2. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons

    PubMed Central

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C.

    2016-01-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca2+ entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca2+ buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca2+-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca2+ elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377724

  3. Impedance and electrically evoked compound action potential (ECAP) drop within 24 hours after cochlear implantation.

    PubMed

    Chen, Joshua Kuang-Chao; Chuang, Ann Yi-Chiun; Sprinzl, Georg Mathias; Tung, Tao-Hsin; Li, Lieber Po-Hung

    2013-01-01

    Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI) insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP) variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈ 2.5 cm) and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001). There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes with long

  4. Impedance and Electrically Evoked Compound Action Potential (ECAP) Drop within 24 Hours after Cochlear Implantation

    PubMed Central

    Chen, Joshua Kuang-Chao; Chuang, Ann Yi-Chiun; Sprinzl, Georg Mathias; Tung, Tao-Hsin; Li, Lieber Po-Hung

    2013-01-01

    Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI) insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP) variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈2.5 cm) and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001). There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes with long

  5. Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

    PubMed Central

    Masoli, Stefano; Solinas, Sergio; D'Angelo, Egidio

    2015-01-01

    The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN). In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs), proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN. PMID:25759640

  6. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons.

    PubMed

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C

    2016-08-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca(2+) entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca(2+) buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca(2+)-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca(2+) elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377724

  7. Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential.

    PubMed

    Chang, C L T; Chen, Yi-Ching; Chen, Hui-Ming; Yang, Ning-Sun; Yang, Wen-Chin

    2013-01-01

    Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers. Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide. This disease is caused by autoimmunity-mediated destruction of pancreatic β-cells, leading to insulin deficiency, hyperglycemia and complications. Currently, there is no cure for type 1 diabetes. Insulin injection is the only medication; however, it accompanies serious medical complications. Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy. Despite recent advances in anti-diabetic strategies, no strategy is clinically successful. How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development. Plants provide an extraordinary source of natural medicines for different diseases. Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry. Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives. In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type-1 diabetes. Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic β-cells. We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes. New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed. PMID:23210779

  8. The role of action potentials in determining neuron-type-specific responses to nitric oxide.

    PubMed

    Estes, Stephen; Zhong, Lei Ray; Artinian, Liana; Tornieri, Karine; Rehder, Vincent

    2015-05-01

    The electrical activity in developing and mature neurons determines the intracellular calcium concentration ([Ca(2+)]i), which in turn is translated into biochemical activities through various signaling cascades. Electrical activity is under control of neuromodulators, which can alter neuronal responses to incoming signals and increase the fidelity of neuronal communication. Conversely, the effects of neuromodulators can depend on the ongoing electrical activity within target neurons; however, these activity-dependent effects of neuromodulators are less well understood. Here, we present evidence that the neuronal firing frequency and intrinsic properties of the action potential (AP) waveform set the [Ca(2+)]i in growth cones and determine how neurons respond to the neuromodulator nitric oxide (NO). We used two well-characterized neurons from the freshwater snail Helisoma trivolvis that show different growth cone morphological responses to NO: B5 neurons elongate filopodia, while those of B19 neurons do not. Combining whole-cell patch clamp recordings with simultaneous calcium imaging, we show that the duration of an AP contributes to neuron-specific differences in [Ca(2+)]i, with shorter APs in B19 neurons yielding lower growth cone [Ca(2+)]i. Through the partial inhibition of voltage-gated K(+) channels, we increased the B19 AP duration resulting in a significant increase in [Ca(2+)]i that was then sufficient to cause filopodial elongation following NO treatment. Our results demonstrate a neuron-type specific correlation between AP shape, [Ca(2+)]i, and growth cone motility, providing an explanation to how growth cone responses to guidance cues depend on intrinsic electrical properties and helping explain the diverse effects of NO across neuronal populations.

  9. A Novel Computational Model of the Human Ventricular Action Potential and Ca Transient

    PubMed Central

    Grandi, Eleonora; Pasqualini, Francesco S.; Bers, Donald M.

    2009-01-01

    We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our aims were to: 1) simulate basic excitation-contraction coupling phenomena; 2) use realistic repolarizing K current densities; 3) reach steady-state. The model relies on the framework of the rabbit myocyte model previously developed by our group, with subsarcolemmal and junctional compartments where ion channels sense higher [Ca] vs. bulk cytosol. Ion channels and transporters have been modeled on the basis of the most recent experimental data from human ventricular myocytes. Rapidly and slowly inactivating components of Ito have been formulated to differentiate between endocardial and epicardial myocytes. Transmural gradients of Ca handling proteins and Na pump were also simulated. The model has been validated against a wide set of experimental data including action potential duration (APD) adaptation and restitution, frequency-dependent increase in Ca transient peak and [Na]i. Interestingly, Na accumulation at fast heart rate is a major determinant of APD shortening, via outward shifts in Na pump and Na-Ca exchange currents. We investigated the effects of blocking K currents on APD and repolarization reserve: IKs block does not affect the former and slightly reduces the latter; IK1 blockade modestly increases APD and more strongly reduces repolarization reserve; IKr blockers significantly prolong APD, an effect exacerbated as pacing frequency is decreased, in good agreement with experimental results in human myocytes. We conclude that this model provides a useful framework to explore excitation-contraction coupling mechanisms and repolarization abnormalities at the single myocyte level. PMID:19835882

  10. [The record of sensitive nerve action potentials. Interelectrode distance in healthy children].

    PubMed

    Arango-Aguilar, Jaime; Fraire-Martínez, María Inés; Sepúlveda-Vildósola, Ana Ana

    2014-01-01

    INTRODUCCIÓN: estudios en adultos muestran que con 3 o 4 cm de distancia entre los electrodos activo y de referencia se obtienen los valores ma´ximos de amplitud y latencia de los potenciales de accio´n nerviosos sensitivos. El objetivo de este estudio fue identificar en niños sanos, las distancia entre los electrodos con la cual los valores de amplitud y latencia pico no difieren significativamente de los obtenidos con la distancia entre los electrodos a la cual se obtienen los valores máximos. ME´TODOS: se colocaron cuatro electrodos de referencia a 1, 2, 3 y 4 cm del electrodo activo. La señal del electrodo activo se registró simultáneamente con un puente físico entre los cuatro canales. Se analizó una muestra de 66 nervios medianos en niños de cinco a nueve años. Los valores máximos de amplitud y latencia se obtuvieron con 4 cm entre los electrodos. Se compararon los valores obtenidos con 4 cm entre los electrodos y con 1, 2 y 3 cm.

  11. The effect of stimulation frequency on the transmural ventricular monophasic action potential in yellowfin tuna Thunnus albacares.

    PubMed

    Patrick, S M; White, E; Brill, R W; Shiels, H A

    2011-02-01

    Monophasic action potentials (MAPs) were recorded from the spongy and compact layers of the yellowfin tuna Thunnus albacares ventricle as stimulation frequency was increased. MAP duration decreased with increase in stimulation frequency in both the spongy and compact myocardial layers, but no significant difference in MAP duration was observed between the layers. PMID:21284642

  12. Inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release evoked by metabotropic agonists and backpropagating action potentials in hippocampal CA1 pyramidal neurons.

    PubMed

    Nakamura, T; Nakamura, K; Lasser-Ross, N; Barbara, J G; Sandler, V M; Ross, W N

    2000-11-15

    We examined the properties of [Ca(2+)](i) changes that were evoked by backpropagating action potentials in pyramidal neurons in hippocampal slices from the rat. In the presence of the metabotropic glutamate receptor (mGluR) agonists t-ACPD, DHPG, or CHPG, spikes caused Ca(2+) waves that initiated in the proximal apical dendrites and spread over this region and in the soma. Consistent with previously described synaptic responses (Nakamura et al., 1999a), pharmacological experiments established that the waves were attributable to Ca(2+) release from internal stores mediated by the synergistic effect of receptor-mobilized inositol 1,4, 5-trisphosphate (IP(3)) and spike-evoked Ca(2+). The amplitude of the changes reached several micromoles per liter when detected with the low-affinity indicators fura-6F, fura-2-FF, or furaptra. Repetitive brief spike trains at 30-60 sec intervals generated increases of constant amplitude. However, trains at intervals of 10-20 sec evoked smaller increases, suggesting that the stores take 20-30 sec to refill. Release evoked by mGluR agonists was blocked by MCPG, AIDA, 4-CPG, MPEP, and LY367385, a profile consistent with the primacy of group I receptors. At threshold agonist concentrations the release was evoked only in the dendrites; threshold antagonist concentrations were effective only in the soma. Carbachol and 5-HT evoked release with the same spatial distribution as t-ACPD, suggesting that the distribution of neurotransmitter receptors was not responsible for the restricted range of regenerative release. Intracellular BAPTA and EGTA were approximately equally effective in blocking release. Extracellular Cd(2+) blocked release, but no single selective Ca(2+) channel blocker prevented release. These results suggest that IP(3) receptors are not associated closely with specific Ca(2+) channels and are not close to each other.

  13. The afterhyperpolarizing potential following a train of action potentials is suppressed in an acute epilepsy model in the rat Cornu Ammonis 1 area.

    PubMed

    Kernig, K; Kirschstein, T; Würdemann, T; Rohde, M; Köhling, R

    2012-01-10

    In hippocampal Cornu Ammonis 1 (CA1) neurons, a prolonged depolarization evokes a train of action potentials followed by a prominent afterhyperpolarizing potential (AHP), which critically dampens neuronal excitability. Because it is not known whether epileptiform activity alters the AHP and whether any alteration of the AHP is independent of inhibition, we acutely induced epileptiform activity by bath application of the GABA(A) receptor blocker gabazine (5 μM) in the rat hippocampal slice preparation and studied its impact on the AHP using intracellular recordings. Following 10 min of gabazine wash-in, slices started to develop spontaneous epileptiform discharges. This disinhibition was accompanied by a significant shift of the resting membrane potential of CA1 neurons to more depolarized values. Prolonged depolarizations (600 ms) elicited a train of action potentials, the number of which was not different between baseline and gabazine treatment. However, the AHP following the train of action potentials was significantly reduced after 20 min of gabazine treatment. When the induction of epileptiform activity was prevented by co-application of 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, 10 μM) and D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 μM) to block α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors, respectively, the AHP was preserved despite of GABA(A) receptor inhibition suggesting that the epileptiform activity was required to suppress the AHP. Moreover, the AHP was also preserved when the slices were treated with the protein kinase blockers H-9 (100 μM) and H-89 (1 μM). These results demonstrate that the AHP following a train of action potentials is rapidly suppressed by acutely induced epileptiform activity due to a phosphorylation process-presumably involving protein kinase A.

  14. Reinforcing Saccadic Amplitude Variability

    ERIC Educational Resources Information Center

    Paeye, Celine; Madelain, Laurent

    2011-01-01

    Saccadic endpoint variability is often viewed as the outcome of neural noise occurring during sensorimotor processing. However, part of this variability might result from operant learning. We tested this hypothesis by reinforcing dispersions of saccadic amplitude distributions, while maintaining constant their medians. In a first experiment we…

  15. Action potentials from ventricular mechanoreceptors stimulated by occlusion of the coronary sinus in the dog

    PubMed Central

    Muers, M. F.; Sleight, P.

    1972-01-01

    1. In experiments to determine the type of intra-cardiac receptors which cause the coronary sinus occlusion reflex, recordings were made from sixty-nine single and small multi-fibre preparations of cardiac vagal afferents in open-chest anaesthetized dogs. 2. Thirty-two fibres were stimulated by occlusion of the coronary sinus outflow through an indwelling Morawitz cannula. No receptors were stimulated during occlusions at peak systolic coronary venous pressures below the threshold for reflex cardiovascular depression. At higher pressures, fibre recruitment and further increases in stimulated discharge were demonstrated. 3. The afferent endings of twenty-nine of these fibres were mechanically localized to the epicardium and myocardium of the left ventricle. Three were in the right ventricle. Seventeen single fibres discharged spontaneously at an average of 0·9 impulses/sec. There was cardiac modulation of both resting and stimulated discharge, with most action potentials in systole. Seven of eight fibres conducted at less than 1·0 m/sec. 4. These ventricular receptors and a further twenty-two otherwise like them but not stimulated by occlusions were designated epi-myocardial receptors. 5. 73% of receptors were stimulated by intrapericardial nicotine (50-100 μg). Presumptively superficial receptors were more sensitive to this stimulus. 6. Epi-myocardial receptors were stimulated by intravenous or intracoronary catecholamines, by electrical stimulation of cardiac sympathetic nerves, and by eliciting the carotid sinus occlusion reflex. Aortic occlusion stimulated 66% of fibres tested, but was a less effective stimulus. After all these stimuli, there was a systolic modulation of discharge in more than 70% of fibres. 7. It was concluded that the epi-myocardial receptors are similar to those previously shown to cause the epicardial chemoreflex, and to participate in the coronary chemoreflex. It is suggested that they are responsive to systolic mechanical changes which

  16. Evaluating potential changes in salmonid rearing capacity from alternative sets of rehabilitation actions in the Trinity River, California

    NASA Astrophysics Data System (ADS)

    Beechie, T. J.; Pess, G. R.; Imaki, H.; Martin, A.; Alvarez, J.; Goodman, D.

    2013-12-01

    River restoration plans often propose numerous rehabilitation actions to address key habitat impairments for salmonids. However, restoration plans rarely propose alternative sets of actions or attempt to quantify the potential benefits to targeted biota. In this paper we use geomorphic and biological analyses to estimate restoration potential for each of 37 reaches in a 64-km section of Trinity River, California from the North Fork Trinity River to Lewiston Dam (the focus of habitat rehabilitation efforts under the Trinity River Restoration Program). We first predicted the channel pattern that might develop based in each reach on slope-discharge criteria, and then used these potential patterns along with floodplain width to estimate the maximum sinuosity that restoration actions could likely achieve, as well as a maximum side-channel length that might be created in each reach. For each scenario, we then used existing stream habitat and juvenile salmonid data from previous studies in the Trinity River and other watersheds to determine current and restored carrying capacity. Potential increases in Chinook and steelhead carrying capacity range from 39% for a relatively realistic estimate of increasing habitat quality (more low velocity areas with cover) to 67% for a more optimistic scenario that increases both sinuosity and habitat quality. Only the most optimistic scenario that increases habitat quality, increases sinuosity, and constructs tens of kilometers of side channels more than doubles potential juvenile salmonid production (140% increase). These quantitative predictions provide a frame of reference for evaluating alternative restoration options, and for setting measurable restoration goals.

  17. Elastic resistance change and action potential generation of non-faradaic Pt/TiO2/Pt capacitors

    NASA Astrophysics Data System (ADS)

    Lim, Hyungkwang; Jang, Ho Won; Lee, Doh-Kwon; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2013-06-01

    Electric current in the mixed ionic-electronic conductor TiO2 is hysteretic, i.e. history-dependent, and its use is versatile in electronic devices. Nowadays, biologically inspired, analogue-type computing systems, known as neuromorphic systems, are being actively investigated owing to their new and intriguing physical concepts. The realization of artificial synapses is important for constructing neuromorphic systems. In mammalians' brains, the plasticity of synapses between neighbouring nerve cells arises from action potential firing. Emulating action potential firing via inorganic systems has therefore become important in neuromorphic engineering. In this work, the current-voltage hysteresis of TiO2-based non-faradaic capacitors is investigated to primarily focus on the correlation between the blocking contact and the elasticity, i.e. non-plasticity, of the capacitors' resistance change, in experimental and theoretical methods. The similarity between the action potential firing behaviour in nerve cells and the elasticity of the non-faradaic capacitors is addressed.Electric current in the mixed ionic-electronic conductor TiO2 is hysteretic, i.e. history-dependent, and its use is versatile in electronic devices. Nowadays, biologically inspired, analogue-type computing systems, known as neuromorphic systems, are being actively investigated owing to their new and intriguing physical concepts. The realization of artificial synapses is important for constructing neuromorphic systems. In mammalians' brains, the plasticity of synapses between neighbouring nerve cells arises from action potential firing. Emulating action potential firing via inorganic systems has therefore become important in neuromorphic engineering. In this work, the current-voltage hysteresis of TiO2-based non-faradaic capacitors is investigated to primarily focus on the correlation between the blocking contact and the elasticity, i.e. non-plasticity, of the capacitors' resistance change, in

  18. Long-term increases in BK potassium channel underlie increased action potential firing in dentate granule neurons following pilocarpine-induced status epilepticus in rats.

    PubMed

    Mehranfard, Nasrin; Gholamipour-Badie, Hamid; Motamedi, Fereshteh; Janahmadi, Mahyar; Naderi, Nima

    2015-01-12

    Temporal lobe epilepsy (TLE) is the most common form of acquired epilepsy in adult. Since dentate gyrus granule cells (GCs) play a critical role in hippocampal seizure generation, it is, therefore, important to understand changes in intrinsic properties of GCs in TLE. In this study, the electrophysiological properties of GCs obtained from epileptic rates were compared with the control group using whole cell patch-clamp recording. Results indicated a significant increase in the number of action potentials (APs) in depolarizing currents of 150 pA, 200 pA, and 250 pA. In addition, there was a significant decrease in AP half-width of GCs. The amplitude of fast afterhyperpolarization (fAHP) in epileptic group significantly decreased compared to control group. Blockade of large conductance calcium activated potassium channel (BK), channels with paxilline and iberiotoxin reversed pilocarpine-induced changes in electrophysiological properties of GCs in epileptic group. These results suggest that the BK channel blockers by reversing the firing properties of GCs might have beneficial preventative effects on pilocarpine-induced electrophysiological changes.

  19. Increased excitability and altered action potential waveform in cerebellar granule neurons of the Ts65Dn mouse model of Down syndrome.

    PubMed

    Usowicz, Maria M; Garden, Claire L P

    2012-07-17

    Down syndrome (DS) is characterized by intellectual disability and impaired motor control. Lack of coordinated movement, poor balance, and unclear speech imply dysfunction of the cerebellum, which is known to be reduced in volume in DS. The principal cause of the smaller cerebellum is a diminished number of granule cells (GCs). These neurons form the 'input layer' of the cerebellar cortex, where sensorimotor information carried by incoming mossy fibers is transformed before it is conveyed to Purkinje cells and inhibitory interneurons. However, it is not known how processing of this information is affected in the hypogranular cerebellum that characterizes DS. Here we explore the possibility that the electrical properties of the surviving GCs are changed. We find that in the Ts65Dn mouse model of DS, GCs have a higher input resistance at voltages approaching the threshold for firing, which causes them to be more excitable. In addition, they fire narrower and larger amplitude action potentials. These subtly modified electrical properties may result in atypical transfer of information at the input layer of the cerebellum.

  20. The Potential of General Classroom Observation: Turkish EFL Teachers' Perceptions, Sentiments, and Readiness for Action

    ERIC Educational Resources Information Center

    Merç, Ali

    2015-01-01

    The purpose of this study was to determine Turkish EFL teachers' attitudes towards classroom observation. 204 teachers from different school settings responded to an online questionnaire. Data were analyzed according to three types of attitudes towards classroom observation: perceptions, sentiments, and readiness for action. The findings revealed…

  1. Action Learning in Higher Education: An Investigation of Its Potential to Develop Professional Capability

    ERIC Educational Resources Information Center

    Lizzio, Alf; Wilson, Keithia

    2004-01-01

    This study investigated the extent to which a course, designed using peer and action learning principles to function as an 'on campus practicum', can develop the professional capabilities of students. As part of their formal coursework, third year behavioural science students, functioning as 'student consultants', entered into a…

  2. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control.

    PubMed

    Bravo, Alejandra; Gill, Sarjeet S; Soberón, Mario

    2007-03-15

    Bacillus thuringiensis Crystal (Cry) and Cytolitic (Cyt) protein families are a diverse group of proteins with activity against insects of different orders--Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as nematodes. Their primary action is to lyse midgut epithelial cells by inserting into the target membrane and forming pores. Among this group of proteins, members of the 3-Domain Cry family are used worldwide for insect control, and their mode of action has been characterized in some detail. Phylogenetic analyses established that the diversity of the 3-Domain Cry family evolved by the independent evolution of the three domains and by swapping of domain III among toxins. Like other pore-forming toxins (PFT) that affect mammals, Cry toxins interact with specific receptors located on the host cell surface and are activated by host proteases following receptor binding resulting in the formation of a pre-pore oligomeric structure that is insertion competent. In contrast, Cyt toxins directly interact with membrane lipids and insert into the membrane. Recent evidence suggests that Cyt synergize or overcome resistance to mosquitocidal-Cry proteins by functioning as a Cry-membrane bound receptor. In this review we summarize recent findings on the mode of action of Cry and Cyt toxins, and compare them to the mode of action of other bacterial PFT. Also, we discuss their use in the control of agricultural insect pests and insect vectors of human diseases. PMID:17198720

  3. Amplitude Modulator Chassis

    SciTech Connect

    Erbert, G

    2009-09-01

    The Amplitude Modulator Chassis (AMC) is the final component in the MOR system and connects directly to the PAM input through a 100-meter fiber. The 48 AMCs temporally shape the 48 outputs of the MOR using an arbitrary waveform generator coupled to an amplitude modulator. The amplitude modulation element is a two stage, Lithium Niobate waveguide device, where the intensity of the light passing through the device is a function of the electrical drive applied. The first stage of the modulator is connected to a programmable high performance Arbitrary Waveform Generator (AWG) consisting of 140 impulse generators space 250 ps apart. An arbitrary waveform is generated by independently varying the amplitude of each impulse generator and then summing the impulses together. In addition to the AWG a short pulse generator is also connected to the first stage of the modulator to provide a sub 100-ps pulse used for timing experiments. The second stage of the modulator is connect to a square pulse generator used to further attenuate any pre or post pulse light passing through the first stage of the modulator. The fast rise and fall time of the square pulse generator is also used to produce fast rise and fall times of the AWG by clipping the AWG pulse. For maximum extinction, a pulse bias voltage is applied to each stage of the modulator. A pulse voltage is applied as opposed to a DC voltage to prevent charge buildup on the modulator. Each bias voltage is adjustable to provide a minimum of 50-dB extinction. The AMC is controlled through ICCS to generate the desired temporal pulse shape. This process involves a closed-loop control algorithm, which compares the desired temporal waveform to the produced optical pulse, and iterates the programming of the AWG until the two waveforms agree within an allowable tolerance.

  4. A Critical Role for Neurofascin in Regulating Action Potential Initiation through Maintenance of the Axon Initial Segment

    PubMed Central

    Zonta, Barbara; Desmazieres, Anne; Rinaldi, Arianna; Tait, Steven; Sherman, Diane L.; Nolan, Matthew F.; Brophy, Peter J.

    2011-01-01

    Summary The axon initial segment (AIS) is critical for the initiation and propagation of action potentials. Assembly of the AIS requires interactions between scaffolding molecules and voltage-gated sodium channels, but the molecular mechanisms that stabilize the AIS are poorly understood. The neuronal isoform of Neurofascin, Nfasc186, clusters voltage-gated sodium channels at nodes of Ranvier in myelinated nerves: here, we investigate its role in AIS assembly and stabilization. Inactivation of the Nfasc gene in cerebellar Purkinje cells of adult mice causes rapid loss of Nfasc186 from the AIS but not from nodes of Ranvier. This causes AIS disintegration, impairment of motor learning and the abolition of the spontaneous tonic discharge typical of Purkinje cells. Nevertheless, action potentials with a modified waveform can still be evoked and basic motor abilities remain intact. We propose that Nfasc186 optimizes communication between mature neurons by anchoring the key elements of the adult AIS complex. PMID:21382554

  5. [Hardware Implementation of Numerical Simulation Function of Hodgkin-Huxley Model Neurons Action Potential Based on Field Programmable Gate Array].

    PubMed

    Wang, Jinlong; Lu, Mai; Hu, Yanwen; Chen, Xiaoqiang; Pan, Qiangqiang

    2015-12-01

    Neuron is the basic unit of the biological neural system. The Hodgkin-Huxley (HH) model is one of the most realistic neuron models on the electrophysiological characteristic description of neuron. Hardware implementation of neuron could provide new research ideas to clinical treatment of spinal cord injury, bionics and artificial intelligence. Based on the HH model neuron and the DSP Builder technology, in the present study, a single HH model neuron hardware implementation was completed in Field Programmable Gate Array (FPGA). The neuron implemented in FPGA was stimulated by different types of current, the action potential response characteristics were analyzed, and the correlation coefficient between numerical simulation result and hardware implementation result were calculated. The results showed that neuronal action potential response of FPGA was highly consistent with numerical simulation result. This work lays the foundation for hardware implementation of neural network. PMID:27079105

  6. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    NASA Technical Reports Server (NTRS)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  7. High-Bandwidth Atomic Force Microscopy Reveals A Mechanical spike Accompanying the Action Potential in mammalian Nerve Terminals

    NASA Astrophysics Data System (ADS)

    Salzberg, Brian M.

    2008-03-01

    Information transfer from neuron to neuron within nervous systems occurs when the action potential arrives at a nerve terminal and initiates the release of a chemical messenger (neurotransmitter). In the mammalian neurohypophysis (posterior pituitary), large and rapid changes in light scattering accompany secretion of transmitter-like neuropeptides. In the mouse, these intrinsic optical signals are intimately related to the arrival of the action potential (E-wave) and the release of arginine vasopressin and oxytocin (S-wave). We have used a high bandwidth (20 kHz) atomic force microscope (AFM) to demonstrate that these light scattering signals are associated with changes in nerve terminal volume, detected as nanometer-scale movements of a cantilever positioned on top of the neurohypophysis. The most rapid mechanical response, the ``spike'', has duration comparable to that of the action potential (˜2 ms) and probably reflects an increase in terminal volume due to H2O movement associated with Na^+-influx. Elementary calculations suggest that two H2O molecules accompanying each Na^+-ion could account for the ˜0.5-1.0 å increase in the diameter of each terminal during the action potential. Distinguishable from the mechanical ``spike'', a slower mechanical event, the ``dip'', represents a decrease in nerve terminal volume, depends upon Ca^2+-entry, as well as on intra-terminal Ca^2+-transients, and appears to monitor events associated with secretion. A simple hypothesis is that this ``dip'' reflects the extrusion of the dense core granule that comprises the secretory products. These dynamic high bandwidth AFM recordings are the first to monitor mechanical events in nervous systems and may provide novel insights into the mechanism(s) by which excitation is coupled to secretion at nerve terminals.

  8. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

    PubMed

    Herde, Michel K; Herbison, Allan E

    2015-11-01

    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  9. Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

    PubMed

    Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M; Shepherd, Samantha; Lemon, Roger N

    2009-12-24

    The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation.

  10. Role of gap junction channel in the development of beat-to-beat action potential repolarization variability and arrhythmias.

    PubMed

    Magyar, Janos; Banyasz, Tamas; Szentandrassy, Norbert; Kistamas, Kornel; Nanasi, Peter P; Satin, Jonathan

    2015-01-01

    The short-term beat-to-beat variability of cardiac action potential duration (SBVR) occurs as a random alteration of the ventricular repolarization duration. SBVR has been suggested to be more predictive of the development of lethal arrhythmias than the action potential prolongation or QT prolongation of ECG alone. The mechanism underlying SBVR is not completely understood but it is known that SBVR depends on stochastic ion channel gating, intracellular calcium handling and intercellular coupling. Coupling of single cardiomyocytes significantly decreases the beat-to-beat changes in action potential duration (APD) due to the electrotonic current flow between neighboring cells. The magnitude of this electrotonic current depends on the intercellular gap junction resistance. Reduced gap junction resistance causes greater electrotonic current flow between cells, and reduces SBVR. Myocardial ischaemia (MI) is known to affect gap junction channel protein expression and function. MI increases gap junction resistance that leads to slow conduction, APD and refractory period dispersion, and an increase in SBVR. Ultimately, development of reentry arrhythmias and fibrillation are associated post-MI. Antiarrhythmic drugs have proarrhythmic side effects requiring alternative approaches. A novel idea is to target gap junction channels. Specifically, the use of gap junction channel enhancers and inhibitors may help to reveal the precise role of gap junctions in the development of arrhythmias. Since cell-to-cell coupling is represented in SBVR, this parameter can be used to monitor the degree of coupling of myocardium.

  11. Coupled iterated map models of action potential dynamics in a one-dimensional cable of cardiac cells

    NASA Astrophysics Data System (ADS)

    Wang, Shihong; Xie, Yuanfang; Qu, Zhilin

    2008-05-01

    Low-dimensional iterated map models have been widely used to study action potential dynamics in isolated cardiac cells. Coupled iterated map models have also been widely used to investigate action potential propagation dynamics in one-dimensional (1D) coupled cardiac cells, however, these models are usually empirical and not carefully validated. In this study, we first developed two coupled iterated map models which are the standard forms of diffusively coupled maps and overcome the limitations of the previous models. We then determined the coupling strength and space constant by quantitatively comparing the 1D action potential duration profile from the coupled cardiac cell model described by differential equations with that of the coupled iterated map models. To further validate the coupled iterated map models, we compared the stability conditions of the spatially uniform state of the coupled iterated maps and those of the 1D ionic model and showed that the coupled iterated map model could well recapitulate the stability conditions, i.e. the spatially uniform state is stable unless the state is chaotic. Finally, we combined conduction into the developed coupled iterated map model to study the effects of coupling strength on wave stabilities and showed that the diffusive coupling between cardiac cells tends to suppress instabilities during reentry in a 1D ring and the onset of discordant alternans in a periodically paced 1D cable.

  12. Elastic resistance change and action potential generation of non-faradaic Pt/TiO2/Pt capacitors.

    PubMed

    Lim, Hyungkwang; Jang, Ho Won; Lee, Doh-Kwon; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2013-07-21

    Electric current in the mixed ionic-electronic conductor TiO2 is hysteretic, i.e. history-dependent, and its use is versatile in electronic devices. Nowadays, biologically inspired, analogue-type computing systems, known as neuromorphic systems, are being actively investigated owing to their new and intriguing physical concepts. The realization of artificial synapses is important for constructing neuromorphic systems. In mammalians' brains, the plasticity of synapses between neighbouring nerve cells arises from action potential firing. Emulating action potential firing via inorganic systems has therefore become important in neuromorphic engineering. In this work, the current-voltage hysteresis of TiO2-based non-faradaic capacitors is investigated to primarily focus on the correlation between the blocking contact and the elasticity, i.e. non-plasticity, of the capacitors' resistance change, in experimental and theoretical methods. The similarity between the action potential firing behaviour in nerve cells and the elasticity of the non-faradaic capacitors is addressed.

  13. Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome.

    PubMed

    Fuller, Scott; Stephens, Jacqueline M

    2015-03-01

    Metabolic syndrome and its complications continue to rise in prevalence and show no signs of abating in the immediate future. Therefore, the search for effective treatments is a high priority in biomedical research. Products derived from botanicals have a time-honored history of use in the treatment of metabolic diseases including type 2 diabetes. Trigonella foenum-graecum, commonly known as fenugreek, is an annual herbaceous plant that has been a staple of traditional herbal medicine in many cultures. Although fenugreek has been studied in both clinical and basic research settings, questions remain about its efficacy and biologic mechanisms of action. Diosgenin, 4-hydroxyisoleucine, and the fiber component of the plant are the most intensively studied bioactive constituents present in fenugreek. These compounds have been demonstrated to exert beneficial effects on several physiologic markers including glucose tolerance, inflammation, insulin action, liver function, blood lipids, and cardiovascular health. Although insights into the molecular mechanisms underlying the favorable effects of fenugreek have been gained, we still do not have definitive evidence establishing its role as a therapeutic agent in metabolic disease. This review aims to summarize the currently available evidence on the physiologic effects of the 3 best-characterized bioactive compounds of fenugreek, with particular emphasis on biologic mechanisms of action relevant in the context of metabolic syndrome. PMID:25770257

  14. Complex Dynamic Thresholds and Generation of the Action Potentials in the Neural-Activity Model

    NASA Astrophysics Data System (ADS)

    Kirillov, S. Yu.; Nekorkin, V. I.

    2016-05-01

    This work is devoted to studying the processes of activation of the neurons whose excitation thresholds are not constant and vary in time (the so-called dynamic thresholds). The neuron dynamics is described by the FitzHugh-Nagumo model with nonlinear behavior of the recovery variable. The neuron response to the external pulsed activating action in the presence of a slowly varying synaptic current is studied within the framework of this model. The structure of the dynamic threshold is studied and its properties depending on the external-action parameters are established. It is found that the formation of the "folds" in the separatrix threshold manifold in the model phase space is a typical feature of the complex dynamic threshold. High neuron sensitivity to the action of the comparatively weak slow control signals is established. This explains the capability of the neurons to perform flexible tuning of their selective properties for detecting various external signals in sufficiently short times (of the order of duration of several spikes).

  15. [The action of ionizing radiation on the central nervous system (based on clinical and polymodal evoked potential data)].

    PubMed

    Shkol'nik, V M; Pogorelov, A V

    1998-05-01

    A clinical examination was done as was an investigation into polymodal evoked potentials (EP) of the brain in the group of 123 liquidators of the accident (LA) to the N 4 reactor unit of the Chernobyl nuclear power station. There was a steady decrease in the amplitude of auditory EP of the brain stem (AEPBS), somatosensory EP, visual EP and a great lengthening of latent periods (LP) of late cortical components H200, II300, H400. LP AEPBS appeared to be intact in 91.5% LA. Correlation was established between the hemodynamic and neurodynamic disorders suggesting to us that further postradiation nosology is brought about by morbid neuronal pattern, the formation of which is determined not only by radiation exposure but acquires the character of a multivariate process. PMID:9695553

  16. Dissociating action inhibition, conflict monitoring and sensory mismatch into independent components of event related potentials in GO/NOGO task.

    PubMed

    Kropotov, Juri D; Ponomarev, Valery A; Hollup, Stig; Mueller, Andreas

    2011-07-15

    The anterior N2 and P3 waves of event related potentials (ERPs) in the GO/NOGO paradigm in trials related to preparatory set violations in previous studies were inconsistently associated either with action inhibition or conflict monitoring operations. In the present study a paired stimulus GO/NOGO design was used in order to experimentally control the preparatory sets. Three variants of the same stimulus task manipulated sensory mismatch, action inhibition and conflict monitoring operations by varying stimulus-response associations. The anterior N2 and P3 waves were decomposed into components by means of independent component analysis (ICA). The ICA was performed on collection of 114 individual ERPs in the three experimental conditions. Three of the independent components were selectively affected by the task manipulations indicating association of these components with sensory mismatch, action inhibition and conflict monitoring operations. According to sLORETA the sensory mismatch component was generated in the left and right temporal areas, the action suppression component was generated in the supplementary motor cortex, and the conflict monitoring component was generated in the anterior cingulate cortex.

  17. Potential of rapid adjustment of brief interceptive action using predicted information.

    PubMed

    Ikudome, Sachi; Nakamoto, Hiroki; Yotani, Kengo; Unenaka, Satoshi; Mori, Shiro

    2015-07-01

    Interceptive actions, such as hitting a ball in baseball or tennis, feature a moving target whose parameters (i.e., velocity or trajectory) differ across trials. This means that players are required to make rapid trial-by-trial adjustments. The purpose of this study was to determine whether a brief interceptive action could be adjusted using predicted sensory consequence of movement (pSCM) information, even under severe time constraints where the participants could not adjust their movement using only visual feedback. Participants performed an interceptive action for targets with two different velocities with different occurrence probabilities (20%, 50%, and 80%). Prior to movement onset, we applied transcranial magnetic stimulation (TMS) to the supplementary motor area (SMA), as TMS of the SMA is known to disrupt pSCM activity. We hypothesized that if pSCM information were used to adjust the motor parameters of a brief interception, then TMS would significantly increase the constant temporal error (i.e., the difference between the sum of reaction time and movement time and the total target visible time) for a target velocity with a low probability (20%). This hypothesis is based on the previous findings that the pSCM plays an important role in the adjustment of relatively brief interception. We found that while interceptions that lasted about 250 ms after movement onset were unaffected, interceptions that lasted about 350 ms after movement onset could be influenced by TMS. However, TMS interfered with performance provided that the delivery of the pulse occurred 100 ms before movement onset. This finding suggests that pSCM information that is used for a rapid adjustment is generated only in that specific time interval. PMID:26010202

  18. Potential of rapid adjustment of brief interceptive action using predicted information.

    PubMed

    Ikudome, Sachi; Nakamoto, Hiroki; Yotani, Kengo; Unenaka, Satoshi; Mori, Shiro

    2015-07-01

    Interceptive actions, such as hitting a ball in baseball or tennis, feature a moving target whose parameters (i.e., velocity or trajectory) differ across trials. This means that players are required to make rapid trial-by-trial adjustments. The purpose of this study was to determine whether a brief interceptive action could be adjusted using predicted sensory consequence of movement (pSCM) information, even under severe time constraints where the participants could not adjust their movement using only visual feedback. Participants performed an interceptive action for targets with two different velocities with different occurrence probabilities (20%, 50%, and 80%). Prior to movement onset, we applied transcranial magnetic stimulation (TMS) to the supplementary motor area (SMA), as TMS of the SMA is known to disrupt pSCM activity. We hypothesized that if pSCM information were used to adjust the motor parameters of a brief interception, then TMS would significantly increase the constant temporal error (i.e., the difference between the sum of reaction time and movement time and the total target visible time) for a target velocity with a low probability (20%). This hypothesis is based on the previous findings that the pSCM plays an important role in the adjustment of relatively brief interception. We found that while interceptions that lasted about 250 ms after movement onset were unaffected, interceptions that lasted about 350 ms after movement onset could be influenced by TMS. However, TMS interfered with performance provided that the delivery of the pulse occurred 100 ms before movement onset. This finding suggests that pSCM information that is used for a rapid adjustment is generated only in that specific time interval.

  19. Effects of muscle action type with equal impulse of conditioning activity on postactivation potentiation.

    PubMed

    Bogdanis, Gregory C; Tsoukos, Athanasios; Veligekas, Panagiotis; Tsolakis, Charilaos; Terzis, Gerasimos

    2014-09-01

    This study investigated the effects of muscle action type during conditioning activity (half-squat) on subsequent vertical jump performance. Fourteen track and field athletes (relative half-squat of 2.3 ± 0.3 times their body weight) completed 4 main trials in a randomized and counterbalanced order 5-7 days apart: (a) concentric (CON) half-squats: 7.5 ± 1.2 repetitions against 90% of 1 repetition maximum (1RM), (b) eccentric (ECC) half-squats: 9.3 ± 1.5 repetitions against 70% of 1RM, and (c) 3 sets of 3-second maximal isometric (ISO) half-squats, (d) a control (CTRL) trial, where subjects rested for 10 minutes. The number of repetitions in CON and ECC was adjusted so that the impulse of the vertical ground reaction force was similar to ISO. Countermovement vertical jump (CMJ) performance was evaluated for 21 minutes after each main trial. Countermovement vertical jump performance in ISO was higher than CTRL from the second to the 10th minute of recovery, whereas CMJ performance in ECC was higher than CTRL from the sixth and 10th minute of recovery. Analysis of the peak individual responses revealed an increase in CMJ performance compared with baseline only in ISO (3.0 ± 1.2%; p = 0.045), whereas no significant increases were observed in ECC and CON. Peak CMJ performance for all subjects in ISO and ECC was achieved within 2-10 minutes after the conditioning muscle actions. Isometric were more effective than CON and ECC muscle actions in increasing explosive leg performance when the impulse of the ground reaction force of the conditioning exercise was equated.

  20. Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanesthetized chinchillas: evidence for increased system gain.

    PubMed

    Qiu, C; Salvi, R; Ding, D; Burkard, R

    2000-01-01

    Carboplatin preferentially destroys inner hair cells (IHCs) in the chinchilla inner ear, while retaining a near-normal outer hair cell (OHC) population. The present study investigated the functional consequences of IHC loss on the compound action potential (CAP), inferior colliculus potential (ICP) and auditory cortex potential (ACP) recorded from chronically implanted electrodes. IHC loss led to a reduction in CAP amplitude that was roughly proportional to IHC loss. The ICP amplitude was typically reduced by IHC loss, but the magnitude of this reduction was generally less than that observed for the CAP. In contrast to the CAP and ICP, ACP amplitudes were generally not reduced following IHC loss. In some animals, the ACP amplitude remained at pre-carboplatin values despite substantial IHC loss. However, in other animals, IHC loss led to an increase ('enhancement') of ACP amplitude. ACP enhancement was greatest at 1-2 weeks post-carboplatin, returning towards baseline amplitudes at 5 weeks post-carboplatin. In other animals, the ACP remained enhanced up to 5 weeks post-carboplatin. We interpret the transient and sustained enhancement of ACP amplitude following partial IHC loss as evidence of functional reorganization occurring at or below the level of the auditory cortex. These results suggest that the gain of the central auditory pathway increases following IHC loss to compensate for the reduced input from the cochlea. PMID:10601720

  1. POTENTIATION OF THE ACTION OF BRADYKININ ON SMOOTH MUSCLE BY CHYMOTRYPSIN, CHYMOTRYPSINOGEN AND TRYPSIN.

    PubMed

    EDERY, H

    1964-04-01

    Chymotrypsin, chymotrypsinogen and trypsin sensitized the guinea-pig isolated ileum and rat isolated uterus preparations to the action of bradykinin, whilst the responses to histamine, acetylcholine and 5-hydroxytryptamine were unaffected. Chymotrypsin caused a quick contraction of the guinea-pig ileum which was abolished by mepyramine and therefore probably mediated by histamine. Trypsin contracted the rat uterus as well as the guinea-pig ileum; the latter contraction was slow, resistant to mepyramine and gave rise to tachyphylaxis. It is suggested that isolated smooth muscle preparations should be treated with chymotrypsin for use in the estimation of minute amounts of bradykinin.

  2. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    NASA Technical Reports Server (NTRS)

    Straus, D. M.

    1983-01-01

    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eliassen-Palm flux are also discussed.

  3. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    NASA Technical Reports Server (NTRS)

    Straus, D. M.

    1983-01-01

    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eiiassen-Palm flux are also discussed.

  4. Overcoming photodamage in second-harmonic generation microscopy: real-time optical recording of neuronal action potentials.

    PubMed

    Sacconi, L; Dombeck, D A; Webb, W W

    2006-02-28

    Second-harmonic generation (SHG) has proven essential for the highest-resolution optical recording of membrane potential (Vm) in intact specimens. Here, we demonstrate single-trial SHG recordings of neuronal somatic action potentials and quantitative recordings of their decay with averaging at multiple sites during propagation along branched neurites at distances up to 350 mum from the soma. We realized these advances by quantifying, analyzing, and thereby minimizing the dynamics of photodamage (PD), a frequent limiting factor in the optical imaging of biological preparations. The optical signal and the PD during SHG imaging of stained cultured Aplysia neurons were examined with intracellular electrode recordings monitoring the resting Vm variations induced by laser-scanning illumination. We found that the PD increased linearly with the dye concentration but grew with the cube of illumination intensity, leading to unanticipated optimization procedures to minimize PD. The addition of appropriate antioxidants in conjunction with an observed Vm recovery after termination of laser scanning further refined the imaging criteria for minimization and control of PD during SHG recording of action potentials. With these advances, the potential of SHG as an effective optical tool for neuroscience investigations is being realized.

  5. Comparison of genetically encoded calcium indicators for monitoring action potentials in mammalian brain by two-photon excitation fluorescence microscopy

    PubMed Central

    Podor, Borbala; Hu, Yi-ling; Ohkura, Masamichi; Nakai, Junichi; Croll, Roger; Fine, Alan

    2015-01-01

    Abstract. Imaging calcium transients associated with neuronal activity has yielded important insights into neural physiology. Genetically encoded calcium indicators (GECIs) offer conspicuous potential advantages for this purpose, including exquisite targeting. While the catalogue of available GECIs is steadily growing, many newly developed sensors that appear promising in vitro or in model cells appear to be less useful when expressed in mammalian neurons. We have, therefore, evaluated the performance of GECIs from two of the most promising families of sensors, G-CaMPs [Nat. Biotechnol. 19(2), 137–141 (2001)11175727] and GECOs [Science 333(6051), 1888–1891 (2011)21903779], for monitoring action potentials in rat brain. Specifically, we used two-photon excitation fluorescence microscopy to compare calcium transients detected by G-CaMP3; GCaMP6f; G-CaMP7; Green-GECO1.0, 1.1 and 1.2; Blue-GECO; Red-GECO; Rex-GECO0.9; Rex-GECO1; Carmine-GECO; Orange-GECO; and Yellow-GECO1s. After optimizing excitation wavelengths, we monitored fluorescence signals associated with increasing numbers of action potentials evoked by current injection in CA1 pyramidal neurons in rat organotypic hippocampal slices. Some GECIs, particularly Green-GECO1.2, GCaMP6f, and G-CaMP7, were able to detect single action potentials with high reliability. By virtue of greatest sensitivity and fast kinetics, G-CaMP7 may be the best currently available GECI for monitoring calcium transients in mammalian neurons. PMID:26158004

  6. The potential for multi-disciplinary primary health care services to take action on the social determinants of health: actions and constraints

    PubMed Central

    2013-01-01

    Background The Commission on the Social Determinants of Health and the World Health Organization have called for action to address the social determinants of health. This paper considers the extent to which primary health care services in Australia are able to respond to this call. We report on interview data from an empirical study of primary health care centres in Adelaide and Alice Springs, Australia. Methods Sixty-eight interviews were held with staff and managers at six case study primary health care services, regional health executives, and departmental funders to explore how their work responded to the social determinants of health and the dilemmas in doing so. The six case study sites included an Aboriginal Community Controlled Organisation, a sexual health non-government organisation, and four services funded and managed by the South Australian government. Results While respondents varied in the extent to which they exhibited an understanding of social determinants most were reflexive about the constraints on their ability to take action. Services’ responses to social determinants included delivering services in a way that takes account of the limitations individuals face from their life circumstances, and physical spaces in the primary health care services being designed to do more than simply deliver services to individuals. The services also undertake advocacy for policies that create healthier communities but note barriers to them doing this work. Our findings suggest that primary health care workers are required to transverse “dilemmatic space” in their work. Conclusions The absence of systematic supportive policy, frameworks and structure means that it is hard for PHC services to act on the Commission on the Social Determinants of Health’s recommendations. Our study does, however, provide evidence of the potential for PHC services to be more responsive to social determinants given more support and by building alliances with communities and

  7. Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials

    PubMed Central

    Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J.

    2014-01-01

    The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models—of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells—to investigate the relative effects of reducing two important voltage-gated Ca currents—the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action

  8. Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated from Rhizoma Chuanxiong): Roles and Mechanisms

    PubMed Central

    Guo, Ming; Liu, Yue; Shi, Dazhuo

    2016-01-01

    Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP's clinical use. PMID:27314011

  9. Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated from Rhizoma Chuanxiong): Roles and Mechanisms.

    PubMed

    Guo, Ming; Liu, Yue; Shi, Dazhuo

    2016-01-01

    Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP's clinical use. PMID:27314011

  10. Larval therapy from antiquity to the present day: mechanisms of action, clinical applications and future potential

    PubMed Central

    Whitaker, Iain S; Twine, Christopher; Whitaker, Michael J; Welck, Mathew; Brown, Charles S; Shandall, Ahmed

    2007-01-01

    When modern medicine fails, it is often useful to draw ideas from ancient treatments. The therapeutic use of fly larvae to debride necrotic tissue, also known as larval therapy, maggot debridement therapy or biosurgery, dates back to the beginnings of civilisation. Despite repeatedly falling out of favour largely because of patient intolerance to the treatment, the practice of larval therapy is increasing around the world because of its efficacy, safety and simplicity. Clinical indications for larval treatment are varied, but, in particular, are wounds infected with multidrug‐resistant bacteria and the presence of significant co‐morbidities precluding surgical intervention. The flies most often used in larval therapy are the facultative calliphorids, with the greenbottle blowfly (Lucilia sericata) being the most widely used species. This review summarises the fascinating and turbulent history of larval therapy from its origin to the present day, including mechanisms of action and evidence for its clinical applications. It also explores future research directions. PMID:17551073

  11. Assessing potential targets of calcium action in light-modulated gravitropism

    NASA Technical Reports Server (NTRS)

    Roux, S. J.

    1995-01-01

    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

  12. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.

    PubMed

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

    2016-04-01

    Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action. PMID:26445809

  13. Mosquito larvicidal and pupaecidal potential of prodigiosin from Serratia marcescens and understanding its mechanism of action.

    PubMed

    Suryawanshi, Rahul K; Patil, Chandrashekhar D; Borase, Hemant P; Narkhede, Chandrakant P; Salunke, Bipinchandra K; Patil, Satish V

    2015-09-01

    Mosquitoes spread lethal diseases like malaria and dengue fever to humans. Considering mosquito vector control as one of the best alternatives to reduce new infections, here we have analyzed the effect of purified pigment prodigiosin extracted from Serratia marcescens (NMCC 75) against larval and pupal stages of Aedes aegypti and Anopheles stephensi mosquitoes. Mosquito larvicidal activities of purified prodigiosin revealed LC50 values of 14 ± 1.2, 15.6 ± 1.48, 18 ± 1.3, 21 ± 0.87 µg/ml against early IInd, IIIrd, IVth instar and pupal stages of Ae. aegypti, respectively. LC50 values for An. stephensi were found to be 19.7 ± 1.12, 24.7 ± 1.47, 26.6 ± 1.67, 32.2 ± 1.79 µg/ml against early IInd, IIIrd, IVth instar and pupae of An. stephensi, respectively. Further investigations toward understanding modes of action revealed variations in the activities of esterases, acetylcholine esterases, phosphatases, proteases and total proteins in the fourth instar larvae of Ae. aegypti indicating intrinsic difference in biochemical features due to prodigiosin treatment. Although there was no inhibition of enzymes like catalase and oxidase but may have profound inhibitory effect on carbonic anhydrase or H(+)-V-ATPase which is indicated by change in the pH of midgut and caeca of mosquito larvae. This reduced pH may be possibly due to the proton pump inhibitory activity of prodigiosin. Pure prodigiosin can prove to be an important molecule for mosquito control at larval and pupal stages of Ae. aegypti and An. stephensi. This is the first report on the mosquito pupaecidal activity of prodigiosin and its possible mechanism of action.

  14. Mechanisms of CaMKII action in long-term potentiation

    PubMed Central

    Lisman, John; Yasuda, Ryohei; Raghavachari, Sridhar

    2014-01-01

    Long-term potentiation (LTP) of synaptic strength occurs during learning and can last for long periods, making it a probable mechanism for memory storage. LTP induction results in calcium entry, which activates calcium–calmodulin-dependent protein kinase II (CaMKII). CaMKII subsequently translocates to the synapse, where it binds to the NMDA-type glutamate receptors and produces potentiation by phosphorylating principal and auxiliary subunits of AMPA-type glutamate receptors. These processes all are localized to stimulated spines and account for the synapse specificity of LTP. In the later stages of LTP, CaMKII has a structural role in enlarging and strengthening the synapse. PMID:22334212

  15. A clinically applicable approach for detecting spontaneous action potential spikes in amyotrophic lateral sclerosis with a linear electrode array.

    PubMed

    Jahanmiri-Nezhad, Faezeh; Li, Xiaoyan; Barkhaus, Paul E; Rymer, William Z; Zhou, Ping

    2014-02-01

    Examination of spontaneous muscle activity is an important part of the routine electromyogram (EMG) in assessing neuromuscular diseases. The EMG is specifically valuable as a diagnostic test in supporting the diagnosis of amyotrophic lateral sclerosis. High-density surface EMG is a relatively new technique that has until now been used in research but has the potential for clinical application. This study presents a simple high-density surface EMG method for automatic detection of spontaneous action potentials from surface electrode array recordings of patients with amyotrophic lateral sclerosis. To reduce computational complexity while maintaining useful information from the electrode array recording, the multichannel high-density surface EMG was transferred to single-dimensional data by calculating the maximum difference across all channels of the electrode array. A spike detection threshold was then set in the single-dimensional domain to identify the firing times of each spontaneous action potential spike, whereas a spike extraction threshold was used to define the onset and offset of the spontaneous spikes. These data were used to extract the spontaneous spike waveforms from the electrode array EMG. A database of detected spontaneous spikes was thus obtained, including their waveforms, on all channels along with their corresponding firing times. This newly developed method makes use of the information from different channels of the electrode array EMG recording. It also has the primary feature of being simple and fast in implementation, with convenient parameter adjustment and user-computer interaction. Hence, it has good possibilities for clinical application.

  16. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study

    PubMed Central

    Popovic, Marko A; Foust, Amanda J; McCormick, David A; Zecevic, Dejan

    2011-01-01

    Abstract The spatial pattern of Na+ channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na+ channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (Vm imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination. PMID:21669974

  17. Exercise-induced expression of cardiac ATP-sensitive potassium channels promotes action potential shortening and energy conservation.

    PubMed

    Zingman, Leonid V; Zhu, Zhiyong; Sierra, Ana; Stepniak, Elizabeth; Burnett, Colin M-L; Maksymov, Gennadiy; Anderson, Mark E; Coetzee, William A; Hodgson-Zingman, Denice M

    2011-07-01

    Physical activity is one of the most important determinants of cardiac function. The ability of the heart to increase delivery of oxygen and metabolic fuels relies on an array of adaptive responses necessary to match bodily demand while avoiding exhaustion of cardiac resources. The ATP-sensitive potassium (K(ATP)) channel has the unique ability to adjust cardiac membrane excitability in accordance with ATP and ADP levels, and up-regulation of its expression that occurs in response to exercise could represent a critical element of this adaption. However, the mechanism by which K(ATP) channel expression changes result in a beneficial effect on cardiac excitability and function remains to be established. Here, we demonstrate that an exercise-induced rise in K(ATP) channel expression enhanced the rate and magnitude of action potential shortening in response to heart rate acceleration. This adaptation in membrane excitability promoted significant reduction in cardiac energy consumption under escalating workloads. Genetic disruption of normal K(ATP) channel pore function abolished the exercise-related changes in action potential duration adjustment and caused increased cardiac energy consumption. Thus, an expression-driven enhancement in the K(ATP) channel-dependent membrane response to alterations in cardiac workload represents a previously unrecognized mechanism for adaptation to physical activity and a potential target for cardioprotection.

  18. Closed string amplitudes as single-valued open string amplitudes

    NASA Astrophysics Data System (ADS)

    Stieberger, Stephan; Taylor, Tomasz R.

    2014-04-01

    We show that the single trace heterotic N-point tree-level gauge amplitude ANHET can be obtained from the corresponding type I amplitude ANI by the single-valued (sv) projection: ANHET=sv(ANI). This projection maps multiple zeta values to single-valued multiple zeta values. The latter represent a subclass of multiple zeta values originating from single-valued multiple polylogarithms at unity. Similar relations between open and closed string amplitudes or amplitudes of different string vacua can be established. As a consequence the α‧-expansion of a closed string amplitude is dictated by that of the corresponding open string amplitude. The combination of single-valued projections, Kawai-Lewellen-Tye relations and Mellin correspondence reveal a unity of all tree-level open and closed superstring amplitudes together with the maximally supersymmetric Yang-Mills and supergravity theories.

  19. Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons

    PubMed Central

    Svirskis, Gytis; Baranauskas, Gytis; Svirskiene, Natasa; Tkatch, Tatiana

    2015-01-01

    The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum. PMID:26414356

  20. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro

    PubMed Central

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C.

    2015-01-01

    Neuron–astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (−astrocyte) within the same culture dish. −Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. SIGNIFICANCE STATEMENT Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform

  1. Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes

    PubMed Central

    Stimers, Joseph R.; Song, Li; Rusch, Nancy J.; Rhee, Sung W.

    2015-01-01

    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome. PMID:26091273

  2. Performance analysis of stationary and discrete wavelet transform for action potential detection from sympathetic nerve recordings in humans.

    PubMed

    Salmanpour, Aryan; Brown, Lyndon J; Shoemaker, J Kevin

    2008-01-01

    Accurate investigation of the sympathetic nervous system is important in the diagnosis and study of various autonomic and cardiovascular control and disorders. Sympathetic function associated with blood pressure regulation in humans can be evaluated by recording muscle sympathetic nerve activity (MSNA), which is characterised by synchronous neuronal discharges separated by periods of neural silence dominated by colored gaussian noise. In this paper two common methods for detecting filtered action potential in MSNA recordings is compared. These methods are based on stationary wavelet transform (SWT) and discrete wavelet transform (DWT). The performance analysis are evaluated using simulated MSNA using templates extracted from real MSNA recorded from three healthy subjects.

  3. Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

    PubMed

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-06-01

    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases. PMID:26677077

  4. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    PubMed

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present.

  5. Opioid antagonist naloxone potentiates anxiogenic-like action of cholecystokinin agonists in elevated plus-maze.

    PubMed

    Kõks, S; Soosaar, A; Võikar, V; Volke, V; Ustav, M; Männistö, P T; Bourin, M; Vasar, E

    1998-06-01

    This study investigated the interplay of cholecystokinin (CCK) and endogenous opioid peptides in the regulation of anxiety. The acute administration of non-selective CCK agonist caerulein (1 and 5 microg/kg) and a selective CCK(B) receptor agonist BOC-CCK-4 (1, 10 and 50 microg/kg) induced a dose-dependent anxiogenic-like action in the plus-maze model of anxiety. BOC-CCK-4 displayed a similar efficacy with caerulein, indicating that the described effect was mediated via CCK(B) receptor subtype. The opioid antagonist naloxone itself (0.5 mg/kg) did not change the exploratory activity of rats in the plus-maze. However, the combination of naloxone with the sub-effective doses of caerulein (1 microg/kg) and BOC-CCK-4 (1 microg/kg) induced a significant inhibition of exploratory behaviour in rats. Accordingly, CCK and endogenous opioid peptides have an antagonistic role in the exploratory model of anxiety in rats.

  6. Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

    PubMed

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-06-01

    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases.

  7. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    PubMed

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present. PMID:26644208

  8. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    PubMed

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  9. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    PubMed

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

  10. Potentiation of acetylcholine action by huperzine-A and physostigmine on some vertebrate effectors, including human iris sphincter muscle.

    PubMed

    Patil, Kaustubha D; Buerki, Robin A; Patil, Popat N

    2003-04-01

    The main objective of this investigation was to compare the acetylcholine potentiating action of huperzine-A with acetylcholinesterase inhibitor physostigmine on the frog rectus abdominus muscle, rat phrenic nerve diaphragm preparation, guinea pig ileum and human iris sphincter muscle. In vitro on the frog rectus abdominus muscle, microM of each alkaloid, incubated for 10 min, shifted the acetylcholine concentration response curve to the left. At EC(50) level, physostigmine potentiated acetylcholine response by 4-fold. The potentiation by huperzine-A was 40-fold. The acetylcholine maximum effect, relative to the control, increased to approximately 130% by each alkaloid. Neurally mediated twitch contraction of the rat diaphragm, a skeletal muscle at 1 microM was also potentiated more by huperzine-A than that by physostigmine. Neuromuscular block by (+)-tubocurarine was reversed more easily by huperzine-A than that by physostigmine. On guinea pig ileum, a 30 nM concentration of each alkaloid incubated for 5 min potentiated acetylcholine (10 nM) by 42%, and 33% for huperzine-A and physostigmine respectively. The difference in potentiation between the alkaloids was not significant. At 300 nM of each alkaloid, intrinsic indirect contractions were observed on the ileum, where the rate of contraction by huperzine-A was faster than that by physostigmine. On the iris sphincter, huperzine-A and physostigmine produced a concentration-dependent effect. Maximum effect after each alkaloid was achieved at 30 microM. Potentiation of acetylcholine response by 0.3 microM huperzine-A after a 10-min incubation was greater than that achieved by physostigmine at an equivalent concentration on the contralateral iris sphincter. In summary, huperzine-A exhibits greater acetylcholine potentiating activity on vertebrate muscles than that produced by physostigmine. The results are discussed in relation to the potential therapeutic value of huperzine-A.

  11. Anti-atherogenic potential of jujube, saffron and barberry: anti-diabetic and antioxidant actions.

    PubMed

    Hemmati, Mina; Zohoori, Elham; Mehrpour, Omid; Karamian, Mehdi; Asghari, Somaye; Zarban, Asghar; Nasouti, Roya

    2015-01-01

    Atherogenic dyslipidemia, characterized by an increased level of lipoprotein (a) and a decreased level of adiponectin, is a major risk factor for cardiovascular diseases in diabetic patients. To reduce cardiovascular risk in diabetic patients, use of agents with antidiabetic and anti-atherogenic potential is required. Using an animal model of diabetes, we investigated the antiatherogenic potential of extracts of three medicinal plants: jujube, barberry, and saffron. For this, serum level of fasting blood glucose, lipid profile, malondialdehyde, total antioxidant capacity, adiponectin and lipoprotein (a) in diabetic control and extract treated groups were measured. Statistical analysis of measurements showed that serum levels of fasting blood glucose, triglyceride, and VLDL decreased significantly (P < 0.05) in all treated groups. Treatment with all extracts reduced lipid peroxidation and increased antioxidant capacity of the experimental diabetic groups. Serum adiponectin levels increased in all treated groups, whereas lipoprotein (a) levels decreased, most markedly when treated with jujube extract. Jujube, saffron, and barberry extracts are beneficial in ameliorating oxidative stress and atherogenic risk of diabetic rats. This highlights the benefits of further investigating the cardio-protective potential of medicinal plant extracts and evaluating their usefulness as cardio protective agents in clinical practice. PMID:26600752

  12. Anti-atherogenic potential of jujube, saffron and barberry: anti-diabetic and antioxidant actions

    PubMed Central

    Hemmati, Mina; Zohoori, Elham; Mehrpour, Omid; Karamian, Mehdi; Asghari, Somaye; Zarban, Asghar; Nasouti, Roya

    2015-01-01

    Atherogenic dyslipidemia, characterized by an increased level of lipoprotein (a) and a decreased level of adiponectin, is a major risk factor for cardiovascular diseases in diabetic patients. To reduce cardiovascular risk in diabetic patients, use of agents with antidiabetic and anti-atherogenic potential is required. Using an animal model of diabetes, we investigated the antiatherogenic potential of extracts of three medicinal plants: jujube, barberry, and saffron. For this, serum level of fasting blood glucose, lipid profile, malondialdehyde, total antioxidant capacity, adiponectin and lipoprotein (a) in diabetic control and extract treated groups were measured. Statistical analysis of measurements showed that serum levels of fasting blood glucose, triglyceride, and VLDL decreased significantly (P < 0.05) in all treated groups. Treatment with all extracts reduced lipid peroxidation and increased antioxidant capacity of the experimental diabetic groups. Serum adiponectin levels increased in all treated groups, whereas lipoprotein (a) levels decreased, most markedly when treated with jujube extract. Jujube, saffron, and barberry extracts are beneficial in ameliorating oxidative stress and atherogenic risk of diabetic rats. This highlights the benefits of further investigating the cardio-protective potential of medicinal plant extracts and evaluating their usefulness as cardio protective agents in clinical practice. PMID:26600752

  13. Transmural Ultrasound Imaging of Thermal Lesion and Action Potential Changes in Perfused Canine Cardiac Wedge Preparations by High Intensity Focused Ultrasound Ablation

    PubMed Central

    Wu, Ziqi; Gudur, Madhu S. R.; Deng, Cheri X.

    2013-01-01

    Intra-procedural imaging is important for guiding cardiac arrhythmia ablation. It is difficult to obtain intra-procedural correlation of thermal lesion formation with action potential (AP) changes in the transmural plane during ablation. This study tested parametric ultrasound imaging for transmural imaging of lesion and AP changes in high intensity focused ultrasound (HIFU) ablation using coronary perfused canine ventricular wedge preparations (n = 13). The preparations were paced from epi/endocardial surfaces and subjected to HIFU application (3.5 MHz, 11 Hz pulse-repetition-frequency, 70% duty cycle, duration 4 s, 3500 W/cm2), during which simultaneous optical mapping (1 kframes/s) using di-4-ANEPPS and ultrasound imaging (30 MHz) of the same transmural surface of the wedge were performed. Spatiotemporally correlated AP measurements and ultrasound imaging allowed quantification of the reduction of AP amplitude (APA), shortening of AP duration at 50% repolarization, AP triangulation, decrease of optical AP rise, and change of conduction velocity along tissue depth direction within and surrounding HIFU lesions. The threshold of irreversible change in APA correlating to lesions was determined to be 43±1% with a receiver operating characteristic (ROC) area under curve (AUC) of 0.96±0.01 (n = 13). Ultrasound imaging parameters such as integrated backscatter, Rayleigh (α) and log-normal (σ) parameters, cumulative extrema of σ were tested, with the cumulative extrema of σ performing the best in detecting lesion (ROC AUC 0.89±0.01, n = 13) and change of APA (ROC AUC 0.79±0.03, n = 13). In conclusion, characteristic tissue and AP changes in HIFU ablation were identified and spatiotemporally correlated using optical mapping and ultrasound imaging. Parametric ultrasound imaging using cumulative extrema of σ can detect HIFU lesion and APA reduction. PMID:24349337

  14. Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: potential therapeutic benefits beyond glycaemic control?

    PubMed Central

    Grieve, David J; Cassidy, Roslyn S; Green, Brian D

    2009-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the small intestine in response to nutrient ingestion. It has wide-ranging effects on glucose metabolism, including stimulation of insulin release, inhibition of glucagon secretion, reduction of gastric emptying and augmentation of satiety. Importantly, the insulinotropic actions of GLP-1 are uniquely dependent on ambient glucose concentrations, and it is this particular characteristic which has led to its recent emergence as a treatment for type 2 diabetes. Although the major physiological function of GLP-1 appears to be in relation to glycaemic control, there is growing evidence to suggest that it may also play an important role in the cardiovascular system. GLP-1 receptors (GLP-1Rs) are expressed in the heart and vasculature of both rodents and humans, and recent studies have demonstrated that GLP-1R agonists have wide-ranging cardiovascular actions, such as modulation of heart rate, blood pressure, vascular tone and myocardial contractility. Importantly, it appears that these agents may also have beneficial effects in the setting of cardiovascular disease (CVD). For example, GLP-1 has been found to exert cardioprotective actions in experimental models of dilated cardiomyopathy, hypertensive heart failure and myocardial infarction (MI). Preliminary clinical studies also indicate that GLP-1 infusion may improve cardiac contractile function in chronic heart failure patients with and without diabetes, and in MI patients after successful angioplasty. This review will discuss the current understanding of GLP-1 biology, examine its emerging cardiovascular actions in both health and disease and explore the potential use of GLP-1 as a novel treatment for CVD. PMID:19681866

  15. Direct inhibition of arcuate proopiomelanocortin neurons: a potential mechanism for the orexigenic actions of dynorphin

    PubMed Central

    Zhang, Xiaobing; van den Pol, Anthony N

    2013-01-01

    Dynorphin, an endogenous ligand of kappa (κ) opioid receptors, has multiple roles in the brain, and plays a positive role in energy balance and food intake. However, the mechanism for this is unclear. With immunocytochemistry, we find that axonal dynorphin immunoreactivity in the arcuate nucleus is strong, and that a large number of dynorphin-immunoreactive boutons terminate on or near anorexigenic proopiomelanocortin (POMC) cells. Here we provide evidence from whole-cell patch-clamp recording that dynorphin-A (Dyn-A) directly and dose-dependently inhibits arcuate nucleus POMC neurons. Dyn-A inhibition was eliminated by the κ opioid receptor antagonist nor-BNI, but not by the μ receptor antagonist CTAP. The inhibitory effect was mimicked by the κ2 receptor agonist GR89696, but not by the κ1 receptor agonist U69593. No presynaptic effect of κ2 agonists was found. These results suggest that Dyn-A inhibits POMC neurons through activation of the κ2 opioid receptor. In whole-cell voltage clamp, Dyn-A opened G-protein-coupled inwardly rectifying potassium (GIRK)-like channels on POMC neurons. Dynorphin attenuated glutamate and GABA neurotransmission to POMC neurons. In contrast to the strong inhibition of POMC neurons by Dyn-A, we found a weaker direct inhibitory effect of Dyn-A on arcuate nucleus neuropeptide Y (NPY) neurons mediated by both κ1 and κ2 receptors. Taken together, these results indicate a direct inhibitory effect of Dyn-A on POMC neurons through activation of the κ2 opioid receptor and GIRK channels. A number of orexigenic hypothalamic neurons release dynorphin along with other neuropeptides. The inhibition of anorexigenic POMC neurons may be one mechanism underlying the orexigenic actions of dynorphin. PMID:23318874

  16. PULSE AMPLITUDE DISTRIBUTION RECORDER

    DOEpatents

    Cowper, G.

    1958-08-12

    A device is described for automatica1ly recording pulse annplitude distribution received from a counter. The novelty of the device consists of the over-all arrangement of conventional circuit elements to provide an easy to read permanent record of the pulse amplitude distribution during a certain time period. In the device a pulse analyzer separates the pulses according to annplitude into several channels. A scaler in each channel counts the pulses and operates a pen marker positioned over a drivable recorder sheet. Since the scalers in each channel have the sanne capacity, the control circuitry permits counting of the incoming pulses until one scaler reaches capacity, whereupon the input is removed and an internal oscillator supplies the necessary pulses to fill up the other scalers. Movement of the chart sheet is initiated wben the first scaler reaches capacity to thereby give a series of marks at spacings proportional to the time required to fill the remaining scalers, and accessory equipment marks calibration points on the recorder sheet to facilitate direct reading of the number of external pulses supplied to each scaler.

  17. In vitro antimalarial activity and chloroquine potentiating action of two bisbenzylisoquinoline enantiomer alkaloids isolated from Strychnopsis thouarsii and Spirospermum penduliflorum.

    PubMed

    Ratsimamanga-Urverg, S; Rasoanaivo, P; Ramiaramanana, L; Milijaona, R; Rafatro, H; Verdier, F; Rakoto-Ratsimamanga, A; Le Bras, J

    1992-12-01

    The bisbenzylisoquinolines 7-O-demethyltetrandrine and limacine, respectively, isolated from Strychnopsis thouarsii Baill. and Spirospermum penduliflorum Thou. were evaluated for their intrinsic antimalarial activity in vitro and chloroquine potentiating action against the chloroquine-resistant Plasmodium falciparum FCM 29 originating from Cameroon. They both showed significant antiplasmodial potency in vitro with very similar IC50 values of respectively, 740 nM and 789 nM (IC50 = 214 nM for chloroquine used as standard drug), which demonstrated that the stereochemistry of the C-1 and C-1' configuration likely plays a role in the chloroquine potentiating effect of these drugs. If confirmed in vivo, these results may account for the traditional use of the two plants as antimalarials and adjuvant to chloroquine in Madagascan folklore remedies. PMID:1484894

  18. Action potentials of HL-1 cells recorded with silicon nanowire transistors

    NASA Astrophysics Data System (ADS)

    Eschermann, Jan Felix; Stockmann, Regina; Hueske, Martin; Vu, Xuan Thang; Ingebrandt, Sven; Offenhäusser, Andreas

    2009-08-01

    Silicon nanowire (NW) transistors were fabricated in a top-down process. These devices were used to record the extracellular potential of the spontaneous activity of cardiac muscle HL-1 cells. Their signals were measured by direct dc sampling of the drain current. An improved signal-to-noise ratio compared to planar field-effect devices was observed. Furthermore the signal shape was evaluated and could be associated to different membrane currents. With these experiments, a qualitative description of the properties of the cell-NW contact was obtained and the suitability of these sensors for electrophysiological measurements in vitro was demonstrated.

  19. Effects of changes in frequency on guinea pig ventricular action potential duration and on QT interval under different experimental conditions.

    PubMed

    von Savigny, L; Hohnloser, S; Antoni, H

    1981-01-01

    Isolated perfused guinea pig hearts (Langendorff preparation) were arrested by carbachol (0.1-0.2 mg/l) and electrically stimulated in the region of the av-conducting system. The QT interval was determined by means of extracellular electrodes at different driving frequencies. Separate experiments were performed on papillary muscles from the right ventricle to measure the duration of the transmembrane action potential under comparable conditions. At 35 degrees C (Ke+ 5.4 mmol/l) increasing the frequency of stimulation (range 12-120/min) caused the action potential duration (APD) to decrease to a greater extent than the QT interval. Stepwise rising of the external K+ concentration up to 16.2 mmol/l produced a nearly parallel shift to the APD-frequency relation to lower values. Again, the QT interval was less affected by increasing the external K+ concentration than the APD. Stepwise reduction of the temperature down to 20 degrees C prolonged the APD as well as the QT interval, the effects being more pronounced at lower than at higher stimulation frequencies. Under all examined experimental conditions, the APD proved to be markedly shorter than the QT interval even when the latter is diminished by the duration of QRS. The results suggest that no close relation exists between the APD and the QT interval. The observed divergencies may be due to functional differences among various parts of the ventricles.

  20. Analytic treatment of the compound action potential: Estimating the summed post-stimulus time histogram and unit response

    NASA Astrophysics Data System (ADS)

    Chertoff, Mark E.

    2004-11-01

    The convolution of an equation representing a summed post-stimulus time histogram computed across auditory nerve fibers [P(t)] with an equation representing a single-unit wave form [U(t)], resulted in an analytic expression for the compound action potential (CAP). The solution was fit to CAPs recorded to low and high frequency stimuli at various signal levels. The correlation between the CAP and the analytic expression was generally greater than 0.90. At high levels the width of P(t) was broader for low frequency stimuli than for high frequency signals, but delays were comparable. This indicates that at high signal levels there is an overlap in the population of auditory nerve fibers contributing to the CAP for both low and high frequency stimuli but low frequencies include contributions from more apical regions. At low signal levels the width of P(t) decreased for most frequencies and delays increased. The frequency of oscillation of U(t) was largest for high frequency stimuli and decreased for low frequency stimuli. The decay of U(t) was largest at 8 kHz and smallest at 1 kHz. These results indicate that the hair cell or neural mechanisms involved in the generation of action potentials may differ along the cochlear partition. .

  1. Endocannabinoids produced upon action potential firing evoke a Cl(-) current via type-2 cannabinoid receptors in the medial prefrontal cortex.

    PubMed

    den Boon, Femke S; Chameau, Pascal; Houthuijs, Kas; Bolijn, Simone; Mastrangelo, Nicolina; Kruse, Chris G; Maccarrone, Mauro; Wadman, Wytse J; Werkman, Taco R

    2014-12-01

    The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently demonstrated. In the present study, we show that the application of the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide [a stable analog of the eCB anandamide (AEA)] can activate CB2Rs of mPFC layer II/III pyramidal neurons, which subsequently induces a Cl(-) current. In addition, we show that action potential (AP) firing evoked by 20-Hz current injections results in an eCB-mediated opening of Cl(-) channels via CB2R activation. This AP-evoked synthesis of eCBs is dependent on the Ca(2+) influx through N-type voltage-gated calcium channels. Our results indicate that 2-AG is the main eCB involved in this process. Finally, we demonstrate that under physiologically relevant intracellular Cl(-) conditions, 20-Hz AP firing leads to a CB2R-dependent reduction in neuronal excitability. Altogether, our data indicate that eCBs released upon action potential firing can modulate, through CB2R activation, neuronal activity in the mPFC. We discuss how this may be a mechanism to prevent excessive neuronal firing.

  2. Ruby laser-assisted depilation: The mode of action and potential ways of improved outcome

    NASA Astrophysics Data System (ADS)

    Topping, Adam Partington

    Aim - To improve efficacy and lessen side effects resulting from normal mode ruby laser (NMRL)-assisted depilation via a greater understanding of its mode of action and the development of novel methods of reducing associated epidermal damage. Employing a thermal imaging camera and ex vivo hair-bearing skin, the targets for the NMRL (pulse duration 900 musec and spot size 7 mm) were defined, the temperatures reached and the heat dissipation rates determined. Production of heat was confined to the hair follicles, with the peak temperatures reached varying considerably between hairs within the same treatment area and also between individuals. Histological assessment for a known indicator of cellular damage (p53 expression) identified the sites and extent of damage, which correlated with the peak temperatures measured. An energy meter was used to detect the penetration of NMRL light through ex vivo skin, which was found to be deeper than previously theorised. The black-haired mouse (C57B1/10) was assessed both macroscopically and histologically and found to be an acceptable animal model of NMRL depilation and associated epidermal damage. Attempts to reduce the epidermal damage by simply stopping the light reaching the epidermis using a chromophore block were assessed. Chromophore did indeed reduce the amount of epidermal damage detected in laser-irradiated ex vivo human skin, whereas in contrast it increased the wounding seen in the much thinner skin of the mouse. Nevertheless the mouse model showed that this technique did not affect the depilation efficacy. An alternative method of reducing epidermal damage using induction of the cells' intrinsic protective mechanisms (heat shock proteins, HSP) was assessed using cultured keratinocytes and the mouse model. Primarily, the sub-lethal temperature optimum for HSP expression in human keratinocytes was determined, then an in vitro model of NMRL-associated epidermal damage was established and the heat pre-treatment assessed

  3. Full one-loop amplitudes from tree amplitudes

    SciTech Connect

    Giele, Walter T.; Kunszt, Zoltan; Melnikov, Kirill; /Hawaii U.

    2008-01-01

    We establish an efficient polynomial-complexity algorithm for one-loop calculations, based on generalized D-dimensional unitarity. It allows automated computations of both cut-constructible and rational parts of one-loop scattering amplitudes from on-shell tree amplitudes. We illustrate the method by (re)-computing all four-, five- and six-gluon scattering amplitudes in QCD at one-loop.

  4. Brown Norway rats, a putative schizophrenia model, show increased electroencephalographic activity at rest and decreased event-related potential amplitude, power, and coherence in the auditory sensory gating paradigm.

    PubMed

    Tomimatsu, Yoshiro; Hibino, Ryosuke; Ohta, Hiroyuki

    2015-08-01

    In recent schizophrenia clinical research, electroencephalographic (EEG) oscillatory activities induced by a sensory stimulus or behavioral tasks have gained considerable interest as functional and pathophysiological biomarkers. The Brown Norway (BN) rat is a putative schizophrenia model that shows naturally low sensorimotor gating and deficits in cognitive performance, although other phenotypes have not been studied. The present study aimed to investigate the neurophysiological features of BN rats, particularly EEG/event-related potential (ERP). EEG activity was recorded at rest and during the auditory sensory gating paradigm under an awake, freely moving condition. Frequency and ERP analysis were performed along with time-frequency analysis of evoked power and intertrial coherence. Compared with Wistar-Kyoto rats, a well-documented control line, BN rats showed increased EEG power at rest, particularly in the theta and gamma ranges. In ERP analysis, BN rats showed reduced N40-P20 amplitude but normal sensory gating. The rats also showed reduced evoked power and intertrial coherence against auditory stimuli. These results suggest that BN rats show features of EEG/ERP measures clinically relevant to schizophrenia and may provide additional opportunities for translational research.

  5. Inhibition of protein import into mitochondria by amphiphilic cations: potential targets and mechanism of action.

    PubMed

    Pavlov, P F; Glaser, E

    1998-11-01

    In this paper we describe for the first time the inhibitory effect of three amphiphilic cations, trifluoperazine, propranolol and dibucaine on mitochondrial protein import. The amphiphilic cations did not affect binding of mitochondrial precursor proteins to mitochondria. Import into mitoplasts was affected in a similar manner to intact mitochondria, indicating that the protein import machinery of the inner membrane of mitochondria was responsible for the observed effect. At concentrations which completely inhibited protein import, the amphiphilic cations did not affect the membrane potential (DeltaPsi) across the inner membrane. The inhibitory potency of amphiphilic cations reflects their lipid/water partition coefficient and relatively high concentrations of the drugs were required for complete inhibition, hence we propose that the mechanism of protein import inhibition by amphiphilic cations is due to membrane perturbing effects. We discuss the implications of our findings in view of the possible connection between various inner mitochondrial membrane channels and the protein import pore.

  6. Regulatory T Cells in Autoimmune Diabetes: Mechanisms of Action and Translational Potential.

    PubMed

    Ovcinnikovs, Vitalijs; Walker, Lucy S K

    2015-01-01

    Since the discovery of specialized T cells with regulatory function, harnessing the power of these cells to ameliorate autoimmunity has been a major goal. Here we collate the evidence that regulatory T cells (Treg) can inhibit Type 1 diabetes in animal models and humans. We discuss the anatomical sites and molecular mechanisms of Treg suppressive function in the Type 1 diabetes setting, citing evidence that Treg can function in both the pancreatic lymph nodes and within the pancreatic lesion. Involvement of the CTLA-4 pathway, as well as TGF-β and IL-2 deprivation will be considered. Finally, we summarize current efforts to manipulate Treg therapeutically in individuals with Type 1 diabetes. The translation of this research area from bench to bedside is still in its infancy, but the remarkable therapeutic potential of successfully manipulating Treg populations is clear to see. PMID:26615100

  7. MIF-1 potentiates the action of tricyclic antidepressants in an animal model of depression.

    PubMed

    Kostowski, W; Danysz, W; Dyr, W; Jankowska, E; Krzaścik, P; Pałejko, W; Stefański, R; Płaźnik, A

    1991-01-01

    In the present paper, the effect of simultaneous treatment of rats with low doses of MIF-1 and tricyclic antidepressants on rat behavior in the forced swim test was studied. It was found that MIF-1 stimulated in a dose-dependent manner "active" behavior of animals in this paradigm. The effect of MIF-1 appeared to be independent of changes in rats' locomotion in the open field test. The combined treatment of rats with MIF-1 (0.01 mg/kg IP) and amitriptyline (5 mg/kg IP) or desipramine (1.25 mg/kg) IP) significantly stimulated active behavior in the forced swim test above the level obtained with each of the drugs given separately. The present data suggest the potential clinical efficacy of a combined therapy of depressive patients with MIF-1 and small doses of tricyclic antidepressants.

  8. 'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells.

    PubMed

    Okamoto, Kazuma; Miyoshi, Shunichiro; Toyoda, Masashi; Hida, Naoko; Ikegami, Yukinori; Makino, Hatsune; Nishiyama, Nobuhiro; Tsuji, Hiroko; Cui, Chang-Hao; Segawa, Kaoru; Uyama, Taro; Kami, Daisuke; Miyado, Kenji; Asada, Hironori; Matsumoto, Kenji; Saito, Hirohisa; Yoshimura, Yasunori; Ogawa, Satoshi; Aeba, Ryo; Yozu, Ryohei; Umezawa, Akihiro

    2007-07-15

    The clinical application of cell transplantation for severe heart failure is a promising strategy to improve impaired cardiac function. Recently, an array of cell types, including bone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and embryonic stem cells, have become important candidates for cell sources for cardiac repair. In the present study, we focused on the placenta as a cell source. Cells from the chorionic plate in the fetal portion of the human placenta were obtained after delivery by the primary culture method, and the cells generated in this study had the Y sex chromosome, indicating that the cells were derived from the fetus. The cells potentially expressed 'working' cardiomyocyte-specific genes such as cardiac myosin heavy chain 7beta, atrial myosin light chain, cardiac alpha-actin by gene chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin 43 by immunohistochemistry. These cells were able to differentiate into cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous pattern of localization at intercellular contact sites after cardiomyogenic differentiation, suggesting that the chorionic mesoderm contained a large number of cells with cardiomyogenic potential. The cells began spontaneously beating 3 days after co-cultivation with murine fetal cardiomyocytes and the frequency of beating cells reached a maximum on day 10. The contraction of the cardiomyocytes was rhythmical and synchronous, suggesting the presence of electrical communication between the cells. Placenta-derived human fetal cells may be useful for patients who cannot supply bone marrow cells but want to receive stem cell-based cardiac therapy.

  9. Competing mechanisms for mapping action-related categorical knowledge and observed actions.

    PubMed

    Candidi, Matteo; Vicario, Carmelo Mario; Abreu, Ana Maria; Aglioti, Salvatore Maria

    2010-12-01

    Responses to pictures of famous tennis and soccer athletes are slower when the responding effector is a hand or foot, respectively, indicating that visual recognition of individuals characterized by skilled motor behavior interferes with the motor reactivity of nonproficient observers. By contrast, directly viewing actions induces motor facilitation, suggesting that actions are mapped in the observers' motor system. Here, we used single-pulse Transcranial Magnetic Stimulation to determine 1) whether observing and recognizing the identity of famous tennis and soccer athletes selectively reduce the corticospinal excitability of arm and leg representations (categorization), 2) whether any athlete-related inhibition effect contrasts the facilitation associated with direct action observation (categorization + action), and 3) whether the classic action observation-related facilitation effect is found when viewing "in action" nonathlete models (action). In 3 experiments, we found that amplitude of motor evoked potentials (MEPs) recorded from leg and arm muscles gradually shifted from reduction to facilitation, moving from the categorization to the action observation tasks. Thus, semantic derivation of motor skills is reflected in limb-specific reduction of MEP amplitude, indicating that even abstract action knowledge is embodied in the motor system and that mapping others' actions on the basis of categorization or of their direct observation relies on competing functional mechanisms.

  10. Potentiation of the actions of acetylcholine, epibatidine, and nicotine by methyllycaconitine at fetal muscle-type nicotinic acetylcholine receptors.

    PubMed

    Green, Benedict T; Welch, Kevin D; Cook, Daniel; Gardner, Dale R

    2011-07-15

    Methyllycaconitine (MLA) is a norditerpenoid alkaloid found in high abundance in toxic Delphinium (larkspur) species. It is a potent and selective antagonist of α(7)-nicotinic acetylcholine receptors, but has not been well investigated for activity aside from receptor antagonism. The aim of this study was to investigate the effects of MLA alone and in combination with acetylcholine, epibatidine, nicotine, and neostigmine for actions other than receptor antagonism in TE-671 cells expressing (α(1))(2)β(1)γδ nicotinic acetylcholine receptors. Ligand activity was assessed through measurements of membrane potential changes in TE-671 cells using a fluorescent membrane potential-sensitive dye and normalized to the maximum response to epibatidine (10μM). MLA was ineffective in changing cell membrane potential in the absence of other receptor agonists. However at nanomolar concentrations, it acted as a co-agonist to potentiate TE-671 cell responses to acetylcholine, epibatidine, nicotine, and neostigmine. These results suggest that the poisoning of cattle by norditerpenoid alkaloids found in larkspur may be more complex than previously determined.

  11. K+ accumulation and K+ conductance inactivation during action potential trains in giant axons of the squid Sepioteuthis.

    PubMed

    Inoue, I; Tsutsui, I; Brown, E R

    1997-04-15

    1. During action potential trains in giant axons from the squid Sepioteuthis, decline of the peak level of the undershoot potential was observed. The time course of the decline of the undershoot could be fitted with a three-exponential function with time constants of approximately 25, approximately 400 and approximately 7,000 ms, respectively. 2. When the osmolarity of the external solution was doubled by adding glucose (1.2 M), the fast component of undershoot decline, but not the medium and slow components, was significantly reduced. 3. Under voltage clamp in high osmolarity solutions where K+ accumulation was completely removed, repeated depolarizing pulses at 40 Hz (designed to mimic a train of action potentials) elicited K+ currents whose peak value declined. The decline is consistent with inactivation of the K+ conductance (gK). The decline of gK was fitted by a two-exponential function with time constants of approximately 400 and approximately 7,000 ms, respectively. 4. Interventions designed to modify Schwann cell physiology, such as high frequency stimulation (100 Hz, 2 min), externally applied ouabain (100-500 microM), L-glutamate (100 microM), ACh (100 microM), Co2+ (5mM), Ba2+ (2mM), or removal of external Ca2+ by EGTA, had no significant effects on the fast, medium or slow components of undershoot decline. 5. The results suggest that the fast component of undershoot decline represents K+ accumulation in the space between Schwann cell and axolemma. The medium and slow components are the result of axonal gK inactivation. Schwann cells appear to be involved in K+ clearance only to the extent that they provide an efficient physical pathway for the clearance of K+ by extracellular diffusion.

  12. K+ accumulation and K+ conductance inactivation during action potential trains in giant axons of the squid Sepioteuthis.

    PubMed Central

    Inoue, I; Tsutsui, I; Brown, E R

    1997-01-01

    1. During action potential trains in giant axons from the squid Sepioteuthis, decline of the peak level of the undershoot potential was observed. The time course of the decline of the undershoot could be fitted with a three-exponential function with time constants of approximately 25, approximately 400 and approximately 7,000 ms, respectively. 2. When the osmolarity of the external solution was doubled by adding glucose (1.2 M), the fast component of undershoot decline, but not the medium and slow components, was significantly reduced. 3. Under voltage clamp in high osmolarity solutions where K+ accumulation was completely removed, repeated depolarizing pulses at 40 Hz (designed to mimic a train of action potentials) elicited K+ currents whose peak value declined. The decline is consistent with inactivation of the K+ conductance (gK). The decline of gK was fitted by a two-exponential function with time constants of approximately 400 and approximately 7,000 ms, respectively. 4. Interventions designed to modify Schwann cell physiology, such as high frequency stimulation (100 Hz, 2 min), externally applied ouabain (100-500 microM), L-glutamate (100 microM), ACh (100 microM), Co2+ (5mM), Ba2+ (2mM), or removal of external Ca2+ by EGTA, had no significant effects on the fast, medium or slow components of undershoot decline. 5. The results suggest that the fast component of undershoot decline represents K+ accumulation in the space between Schwann cell and axolemma. The medium and slow components are the result of axonal gK inactivation. Schwann cells appear to be involved in K+ clearance only to the extent that they provide an efficient physical pathway for the clearance of K+ by extracellular diffusion. PMID:9147323

  13. Antioxidant action and potential antidiabetic properties of an isoflavonoid-containing soyabean phytochemical extract (SPE).

    PubMed

    Vedavanam, K; Srijayanta, S; O'Reilly, J; Raman, A; Wiseman, H

    1999-11-01

    The potential role of oestrogenic agents, antioxidants and intestinal glucose-uptake inhibitors in the treatment of diabetes is briefly reviewed. Reports in the literature suggest that oestrogen replacement therapy may favourably modulate glucose homeostasis. A soya phytochemical extract (SPE) containing the isoflavone phytoestrogens genistein and daidzein (mostly in their glycone forms as genistin and daidzin) was investigated as an antioxidant and modulator of intestinal glucose-transport. In the present study, SPE was found to protect against glucose-induced oxidation of human low density lipoproteins (LDL) in vitro. Equol (a gut bacterial metabolite of daidzein) was a more effective antioxidant than daidzein or genistein in this system and was of similar antioxidant potency to the dietary flavonols quercetin and kaempferol and to the endogenous antioxidant 17beta-oestradiol. SPE was found to be an inhibitor of glucose uptake into rabbit intestinal brush border membrane vesicles in vitro, though of weaker potency than the classical sodium dependent glucose transporter (SGLT) inhibitor, phlorizin. Thus SPE displays a range of properties which may be of benefit in diabetes, namely as an oestrogenic agent, an inhibitor of intestinal glucose-uptake and a preventive agent for glucose-induced lipid peroxidation. PMID:10548755

  14. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action

    PubMed Central

    Jeong, Rae-Dong; Chu, Eun-Hee; Park, Duck Hwan; Park, Hae-Jun

    2016-01-01

    Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc). Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika. PMID:27147935

  15. Anthocyanins in obesity-associated thrombogenesis: a review of the potential mechanism of action.

    PubMed

    Thompson, Kiara; Pederick, Wayne; Santhakumar, Abishek Bommannan

    2016-05-18

    Platelet dysfunction, oxidative stress and dyslipidemia are important contributors to pro-thrombotic progression particularly in obese and hyper-cholesterolemic populations. Becoming an increasingly widespread endemic, obesity causes a dysfunction in the metabolic system by initiating endothelial dysfunction; increasing free radical production; lipid peroxidation; platelet hyperactivity and aggregation; thereby accelerating thrombogenesis. In the event of increased free radical generation under pro-thrombotic conditions, antioxidants act as scavengers in reducing physiological oxidative stress; free radical-mediated thrombosis and hemostatic function. Anthocyanin, a subclass of the polyphenol family flavonoids has been shown to exhibit anti-dyslipidemic and anti-thrombotic properties by virtue of its antioxidant activity. Current anti-platelet/coagulant therapeutics target specific receptor pathways to relieve the extent of dysfunction and plaque acceleration in pro-thrombotic individuals. Though effective, they have been associated with high bleeding risk and increased response variability. The following review focuses on the potential role of natural dietary anthocyanins in targeting simultaneous mechanistic pathways in alleviating platelet activation, dyslipidemia, and oxidative stress-associated thrombus acceleration in obese pro-thrombotic populations. PMID:27043127

  16. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis.

    PubMed

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah; Villar, Luisa Maria; Reynolds, Richard; Mikol, Daniel

    2016-01-01

    Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events, including persistent microglial activation that may lead to chronic demyelination and neurodegeneration associated with irreversible disability. In patients with relapsing forms of MS, natalizumab therapy is known to significantly reduce intrathecal inflammatory responses which results in reductions in brain lesions and brain atrophy as well as beneficial effects on clinical measures, such as reduced frequency and severity of relapse and reduced accumulation of disability. Natalizumab treatment also reduces levels of cerebrospinal fluid chemokines and other biomarkers of intrathecal inflammation, axonal damage and demyelination, and has demonstrated the ability to reduce innate immune activation and intrathecal immunoglobulin synthesis in patients with MS. The efficacy of natalizumab therapy in SPMS is currently being investigated in a randomized, double-blind, placebo-controlled trial. PMID:26788129

  17. Feynman amplitudes with confinement included

    NASA Astrophysics Data System (ADS)

    Simonov, Yu. A.

    2009-07-01

    Amplitudes for any multipoint Feynman diagram are written taking into account vacuum background confining field. Higher order gluon exchanges are treated within background perturbation theory. For amplitudes with hadrons in initial or final states vertices are shown to be expressed by the corresponding wave function with the renormalized z factors. Examples of two-point functions, three-point functions (form factors), and decay amplitudes are explicitly considered.

  18. Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma.

    PubMed

    Tetzlaff, Michael T; Singh, Rajesh R; Seviour, Elena G; Curry, Jonathan L; Hudgens, Courtney W; Bell, Diana; Wimmer, Daniel A; Ning, Jing; Czerniak, Bogdan A; Zhang, Li; Davies, Michael A; Prieto, Victor G; Broaddus, Russell R; Ram, Prahlad; Luthra, Rajyalakshmi; Esmaeli, Bita

    2016-09-01

    Sebaceous carcinoma (SC) is a rare but aggressive malignancy with frequent recurrence and metastases. Surgery is the mainstay of therapy, but effective systemic therapies are lacking because the molecular alterations driving SC remain poorly understood. To identify these, we performed whole-exome next-generation sequencing of 409 cancer-associated genes on 27 SCs (18 primary/locally recurrent ocular, 5 paired metastatic ocular, and 4 primary extraocular) from 20 patients. In ocular SC, we identified 139 non-synonymous somatic mutations (median/lesion 3; range 0-23). Twenty-five of 139 mutations (18%) occurred in potentially clinically actionable genes in 6 of 16 patients. The most common mutations were mutations in TP53 (n = 9), RB1 (n = 6), PIK3CA (n = 2), PTEN (n = 2), ERBB2 (n = 2), and NF1 (n = 2). TP53 and RB1 mutations were restricted to ocular SC and correlated with aberrant TP53 and RB protein expression. Systematic pathway analyses demonstrated convergence of these mutations to activation of the PI3K signalling cascade, and PI3K pathway activation was confirmed in tumours with PTEN and/or PIK3CA mutations. Considerable inter-tumoural heterogeneity was observed between paired primary and metastatic ocular SCs. In primary extraocular SC, we identified 77 non-synonymous somatic mutations (median/lesion 22.5; range 3-29). This overall higher mutational load was attributed to a microsatellite instability phenotype in three of four patients and somatically acquired mutations in mismatch repair genes in two of four patients. Eighteen of 77 mutations (23%) were in potentially clinically actionable genes in three of four patients, including BTK, FGFR2, PDGFRB, HRAS, and NF1 mutations. Identification of potentially clinically actionable mutations in 9 of 20 SC patients (45%) underscores the importance of next-generation sequencing to expand the spectrum of genotype-matched targeted therapies. Frequent activation of PI3K signalling pathways provides a strong

  19. Application of the F-Response for Estimating Motor Unit Number and Amplitude Distribution in Hand Muscles of Stroke Survivors.

    PubMed

    Li, Xiaoyan; Fisher, Morris; Rymer, William Zev; Zhou, Ping

    2016-06-01

    The F-response was used in this study to assess changes in the first dorsal interosseous (FDI) muscle after a hemispheric stroke. The number of motor units and their sizes were estimated bilaterally in 12 stroke survivors by recording both the compound muscle action potential (CMAP) and F wave responses. These F waves were induced by applying a large number of electrical stimuli to the ulnar nerve. The amplitude distribution of individual motor unit action potentials (MUAPs) was also compared between paretic and contralateral muscles. When averaged across all the subjects, a significantly lower motor unit number estimate was obtained for the paretic FDI muscle ( 88 ±13) compared with the contralateral side ( 139 ±11) ( ). Pooled surface MUAP amplitude analysis demonstrated a right-skewed distribution for both paretic (kurtosis 3.0) and contralateral (kurtosis 8.52) muscles. When normalized to each individual muscle's CMAP, the surface MUAP amplitude ranged from 0.22% to 4.94% (median 1.17%) of CMAP amplitude for the paretic muscle, and from 0.13% to 3.2% (median 0.62%) of CMAP amplitude for the contralateral muscle. A significant difference in MUAP outliers was also observed between the paretic and contralateral muscles. The findings of this study suggest significant motor unit loss and muscle structural reorganization after stroke. PMID:26168437

  20. Single unit action potentials in humans and the effect of seizure activity

    PubMed Central

    Merricks, Edward M.; Smith, Elliot H.; McKhann, Guy M.; Goodman, Robert R.; Bateman, Lisa M.; Emerson, Ronald G.

    2015-01-01

    Spike-sorting algorithms have been used to identify the firing patterns of isolated neurons (‘single units’) from implanted electrode recordings in patients undergoing assessment for epilepsy surgery, but we do not know their potential for providing helpful clinical information. It is important therefore to characterize both the stability of these recordings and also their context. A critical consideration is where the units are located with respect to the focus of the pathology. Recent analyses of neuronal spiking activity, recorded over extended spatial areas using microelectrode arrays, have demonstrated the importance of considering seizure activity in terms of two distinct spatial territories: the ictal core and penumbral territories. The pathological information in these two areas, however, is likely to be very different. We investigated, therefore, whether units could be followed reliably over prolonged periods of times in these two areas, including during seizure epochs. We isolated unit recordings from several hundred neurons from four patients undergoing video-telemetry monitoring for surgical evaluation of focal neocortical epilepsies. Unit stability could last in excess of 40 h, and across multiple seizures. A key finding was that in the penumbra, spike stereotypy was maintained even during the seizure. There was a net tendency towards increased penumbral firing during the seizure, although only a minority of units (10–20%) showed significant changes over the baseline period, and notably, these also included neurons showing significant reductions in firing. In contrast, within the ictal core territories, regions characterized by intense hypersynchronous multi-unit firing, our spike sorting algorithms failed as the units were incorporated into the seizure activity. No spike sorting was possible from that moment until the end of the seizure, but recovery of the spike shape was rapid following seizure termination: some units reappeared within tens of

  1. On the Period-Amplitude and Amplitude-Period Relationships

    NASA Technical Reports Server (NTRS)

    Wilson, Robert M.; Hathaway, David H.

    2008-01-01

    Examined are Period-Amplitude and Amplitude-Period relationships based on the cyclic behavior of the 12-month moving averages of monthly mean sunspot numbers for cycles 0.23, both in terms of Fisher's exact tests for 2x2 contingency tables and linear regression analyses. Concerning the Period-Amplitude relationship (same cycle), because cycle 23's maximum amplitude is known to be 120.8, the inferred regressions (90-percent prediction intervals) suggest that its period will be 131 +/- 24 months (using all cycles) or 131 +/- 18 months (ignoring cycles 2 and 4, which have the extremes of period, 108 and 164 months, respectively). Because cycle 23 has already persisted for 142 months (May 1996 through February 2008), based on the latter prediction, it should end before September 2008. Concerning the Amplitude-Period relationship (following cycle maximum amplitude versus preceding cycle period), because cycle 23's period is known to be at least 142 months, the inferred regressions (90-percent prediction intervals) suggest that cycle 24's maximum amplitude will be about less than or equal to 96.1 +/- 55.0 (using all cycle pairs) or less than or equal to 91.0 +/- 36.7 (ignoring statistical outlier cycle pairs). Hence, cycle 24's maximum amplitude is expected to be less than 151, perhaps even less than 128, unless cycle pair 23/24 proves to be a statistical outlier.

  2. Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

    PubMed

    Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

    2016-05-01

    It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG.

  3. Ajoene, the antiplatelet principle of garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole on human platelets.

    PubMed

    Apitz-Castro, R; Escalante, J; Vargas, R; Jain, M K

    1986-05-01

    Ajoene, the major antiplatelet compound derived from garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole. For collagen-induced platelet aggregation in human PRP, the ID50 for ajoene is 95 +/- 5 microM. However, in the presence of the antiaggregatory drugs mentioned above, the ID50 for ajoene decreases more than what would be predicted on the basis of simple additive effects. Similarly, the ID50 for prostacyclin decreases from 1 nM to 0.15 nM in the presence of 80 microM ajoene. Isobolic curves for the various combinations of ajoene with prostacyclin or indomethacin exhibit departure from linearity, as predicted for a potentiated synergism between ajoene and these drugs. Dypiridamole, which in PRP has very little effect on the dose-response curve for ajoene, when assayed in whole blood decreases the ID50 for ajoene by a factor of four. These results demonstrate that the antithrombotic potential of ajoene is substantially increased in the presence of physiologically and pharmacologically active antiplatelet agents.

  4. Promoting HIV Vaccine Research in African American Communities: Does the Theory of Reasoned Action Explain Potential Outcomes of Involvement?

    PubMed

    Frew, Paula M; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J

    2007-01-01

    The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (>/= 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research.

  5. Encoding for computation: Recognizing brief dynamical patterns by exploiting effects of weak rhythms on action-potential timing

    PubMed Central

    Hopfield, J. J.

    2004-01-01

    Many stimuli have meaning only as patterns over time. Most auditory and many visual stimuli are of this nature and can be described as multidimensional, time-dependent vectors. A simple neuron can encode a single component of the vector in a firing rate. The addition of a small subthreshold oscillatory current perturbs the action-potential timing, encoding the signal also in a timing relationship, with little effect on the coexisting firing rate representation. When the subthreshold signal is common to a group of neurons, the timing-based information is significant to neurons receiving inputs from the group. This information encoding allows simple implementation of computations not readily done with rate coding. These ideas are examined by using speech to provide a realistic input signal to a biologically inspired model network of spiking neurons. The output neurons of the two-layer system are shown to specifically encode short linguistic elements of speech. PMID:15075391

  6. Dendritic Na(+) spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons.

    PubMed

    Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

    2014-01-01

    Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na(+) spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na(+) spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow.

  7. Nerve-released acetylcholine contracts urinary bladder smooth muscle by inducing action potentials independently of IP3-mediated calcium release.

    PubMed

    Nausch, Bernhard; Heppner, Thomas J; Nelson, Mark T

    2010-09-01

    Nerve-released ACh is the main stimulus for contraction of urinary bladder smooth muscle (UBSM). Here, the mechanisms by which ACh contracts UBSM are explored by determining Ca(2+) and electrical signals induced by nerve-released ACh. Photolysis of caged inositol 1,4,5-trisphosphate (IP(3)) evoked Ca(2+) release from the sarcoplasmic reticulum. Electrical field stimulation (20 Hz) induced Ca(2+) waves within the smooth muscle that were present only during stimulus application. Ca(2+) waves were blocked by inhibition of muscarinic ACh receptors (mAChRs) with atropine and depletion of sarcoplasmic reticulum Ca(2+) stores with cyclopiazonic acid (CPA), and therefore likely reflect activation of IP(3) receptors (IP(3)Rs). Electrical field stimulation also increased excitability to induce action potentials (APs) that were accompanied by Ca(2+) flashes, reflecting Ca(2+) entry through voltage-dependent Ca(2+) channels (VDCCs) during the action potential. The evoked Ca(2+) flashes and APs occurred as a burst with a lag time of approximately 1.5 s after onset of stimulation. They were not inhibited by blocking IP(3)-mediated Ca(2+) waves, but by blockers of mAChRs (atropine) and VDCCs (diltiazem). Nerve-evoked contractions of UBSM strips were greatly reduced by blocking VDCCs, but not by preventing IP(3)-mediated Ca(2+) signaling with cyclopiazonic acid or inhibition of PLC with U73122. These results indicate that ACh released from nerve varicosities induces IP(3)-mediated Ca(2+) waves during stimulation; but contrary to expectations, these signals do not appear to participate in contraction. In addition, our data provide compelling evidence that UBSM contractions evoked by nerve-released ACh depend on increased excitability and the resultant Ca(2+) entry through VDCCs during APs.

  8. Changes in contractile properties and action potentials of motor units in the rat medial gastrocnemius muscle during maturation.

    PubMed

    Dobrzynska, Z; Celichowski, J

    2016-02-01

    The early phase of development of muscles stops following the disappearance of embryonic and neonatal myosin and the elimination of polyneuronal innervation of muscle fibres with the formation of motor units (MUs), but later the muscle mass still considerably increases. It is unknown whether the three types are visible among newly formed MUs soon after the early postnatal period and whether their proportion is similar to that in adult muscle. Moreover, the processes responsible for MU-force regulation by changes in motoneuronal firing rate as well as properties of motor unit action potentials (MUAPs) during maturation are unknown. Three groups of Wistar rats were investigated - 1 month old, 2 months old and the adult, 9 months old. The basic contractile properties and action potentials of MUs in the medial gastrocnemius (MG) muscle were analysed. The three types of MUs were distinguishable in all age groups, but higher proportion of slow MUs was noticed in young rats (29%, 18% and 11% in 1, 2 and 9 months rats, respectively). The fatigue index for fast fatigable MUs in 1 month old rats was about 2 times higher than in 9 months old rats. The twitch time parameters of fast MUs were shortened during the maturation; for these units, the force-frequency curves in young rats were shifted towards lower frequencies, which suggested that fast motoneurons of young animals generate lower firing rates. Higher twitch-to-tetanus ratios noted for the three MU types in young rats suggested the smaller role of rate coding in force regulation processes, and the higher role of MU recruitment in young rats. No significant differences in MUAP parameters between two groups of young and adult animals were observed. Concluding, the maturation process evokes deeper changes in fast MUs than in slow ones. PMID:27010903

  9. Auditory steady-state evoked potentials vs. compound action potentials for the measurement of suppression tuning curves in the sedated dog puppy.

    PubMed

    Markessis, Emily; Poncelet, Luc; Colin, Cécile; Hoonhorst, Ingrid; Collet, Grégory; Deltenre, Paul; Moore, Brian C J

    2010-06-01

    Auditory steady-state evoked potential (ASSEP) tuning curves were compared to compound action potential (CAP) tuning curves, both measured at 2 Hz, using sedated beagle puppies. The effect of two types of masker (narrowband noise and sinusoidal) on the tuning curve parameters was assessed. Whatever the masker type, CAP tuning curve parameters were qualitatively and quantitatively similar to the ASSEP ones, with a similar inter-subject variability, but with a greater incidence of upward tip displacement. Whatever the procedure, sinusoidal maskers produced sharper tuning curves than narrow-band maskers. Although these differences are not likely to have significant implications for clinical work, from a fundamental point of view, their origin requires further investigations. The same amount of time was needed to record a CAP and an ASSEP 13-point tuning curve. The data further validate the ASSEP technique, which has the advantages of having a smaller tendency to produce upward tip shifts than the CAP technique. Moreover, being non invasive, ASSEP tuning curves can be easily repeated over time in the same subject for clinical and research purposes.

  10. Does the maximum upstroke velocity of the action potential (Vmax) represent available sodium conductance in frog ventricular cells?

    PubMed

    Yamaoka, K

    1987-01-01

    In examining the relation between the maximum upstroke velocity of the action potential (Vmax) and available Na conductance (agNa), the dose-response curve for tetrodotoxin (TTX) and the steady-state inactivation (h infinity)-membrane potential curve were obtained by measuring Na current (INa) as well as Vmax in single isolated frog ventricular cells. The present experiment demonstrated that the relation between Vmax and agNa is linear. On the other hand, simulation analysis of this relation in the absence of leakage current (IL), in which the necessary parameters for INa had been determined by the voltage clamp experiment, showed non-linear properties. The non-linear relation originates from the fact that kinetic variable, m, and driving force for INa at the time of Vmax is not constant with respect to the change in either hO or gNa. A reasonable explanation for this discrepancy is that the presence of IL suppresses the total ionic current at the time of Vmax and hence the change in INa does not straightforwardly reflect that in Vmax.

  11. The formation of correlated states and optimization of the tunnel effect for low-energy particles under nonmonochromatic and pulsed action on a potential barrier

    NASA Astrophysics Data System (ADS)

    Vysotskii, V. I.; Vysotskyy, M. V.

    2015-10-01

    We consider peculiarities of the formation of a coherent correlated state (CCS) of a low-energy particle under frequency modulation of parameters of a harmonic oscillator that contains this particle by a broadband nonmonochromatic or asymmetric pulsed action. It is shown that in the case of modulation with frequency-normalized intensity, the maximum efficiency of CCS formation corresponds to a narrow-band action, while broadband modulation is optimal for the action with a constant spectral density. As in the case of monochromatic modulation, the maximum correlation coefficient, | r|max, under the nonmonochromatic action corresponds to parametric resonance at frequency Ω ≈ 2ω0. Under a pulsed action, the maximum efficiency of CCS formation and, hence, the maximum probability of the tunnel effect, correspond to pulsed modulation with a short leading edge and a long trailing edge. In particular, under the action of a pulsed magnetic field with an amplitude of 10 kOe and the leading edge duration of 2 × 10-7 s on a gas with deuterium ions, a CCS can be formed with the correlation coefficient | r|max ≈ 0.9998, for which the tunneling effect probability under the dd interaction at temperature T ≈ 300-500 K increases from D r = 0 ≈ 10-80 to {D_{|r{|_{max }} = 0.9998}} ≈ 0.1. This process can occur in a gas with particle number density n < n cr ≈ 1017 cm-3. The method of CCS formation makes it possible to explain the results of an experiment in which substantial isotope changes were detected when a pulsed electric current and magnetic-field generation occurred.

  12. Action Learning: Avoiding Conflict or Enabling Action

    ERIC Educational Resources Information Center

    Corley, Aileen; Thorne, Ann

    2006-01-01

    Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

  13. Effect of phentolamine, alprenolol and prenylamine on maximum rate of rise of action potential in guinea-pig papillary muscles.

    PubMed

    Sada, H

    1978-10-01

    Effects of phentolamine (13.3, 26.5 and 53.0 micron), alprenolol (3.5, 7.0 and 17.5 micron) and prenylamine (2.4, 4.8 and 11.9 micron) on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with Tyrode's solution. 1. Phentolamine, alprenolol and prenylamine reduced the maximum rate of rise of action potential (.Vmax) dose-dependently. Higher concentrations of phentolamine and prenylamine caused a loss of plateau in a majority of the preparations. Resting potential was not altered by any of the drugs. Readmittance of drug-free Tyrode's solution reversed these changes induced by 13.3 micron of phentolamine and all conconcentrations of alprenolol almost completely but those induced by higher concentrations of phentolamine and all concentrations of prenylamine only slightly. 2. .Vmax at steady state was increased with decreasing driving frequencies (0.5 and 0.25 Hz) and was decreased with increasing ones (2--5 Hz) in comparison with that at 1 Hz. Such changes were all exaggerated by the above drugs, particularly by prenylamine. 3. Prenylamine and, to a lesser degree, phentolamine and alprenolol delayed dose-dependently the recovery process of .Vmax in premature responses. 4. .Vmax in the first response after interruption of stimulation recovered toward the predrug value in the presence of the above three drugs. The time constants of recovery process ranged between 10.5 and 15.0s for phentolamine, between 4.5 and 15.5s for alprenolol. The time constant of the main component was estimated to be approximately 2s for the recovery process with prenylamine. 5. On the basis of the model recently proposed by Hondeghem and Katzung (1977), it is suggested that the drug molecules associate with the open sodium channels and dissociated slowly from the closed channels and that the inactivation parameter in the drug-associated channels is shifted in the hyperpolarizing direction.

  14. Action potential characterization of human induced pluripotent stem cell-derived cardiomyocytes using automated patch-clamp technology.

    PubMed

    Scheel, Olaf; Frech, Stefanie; Amuzescu, Bogdan; Eisfeld, Jörg; Lin, Kun-Han; Knott, Thomas

    2014-10-01

    Recent progress in embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) research led to high-purity preparations of human cardiomyocytes (CMs) differentiated from these two sources-suitable for tissue regeneration, in vitro models of disease, and cardiac safety pharmacology screening. We performed a detailed characterization of the effects of nifedipine, cisapride, and tetrodotoxin (TTX) on Cor.4U(®) human iPSC-CM, using automated whole-cell patch-clamp recordings with the CytoPatch™ 2 equipment, within a complex assay combining multiple voltage-clamp and current-clamp protocols in a well-defined sequence, and quantitative analysis of several action potential (AP) parameters. We retrieved three electrical phenotypes based on AP shape: ventricular, atrial/nodal, and S-type (with ventricular-like depolarization and lack of plateau). To suppress spontaneous firing, present in many cells, we injected continuously faint hyperpolarizing currents of -10 or -20 pA. We defined quality criteria (both seal and membrane resistance over 1 GΩ), and focused our study on cells with ventricular-like AP. Nifedipine induced marked decreases in AP duration (APD): APD90 (49.8% and 40.8% of control values at 1 and 10 μM, respectively), APD50 (16.1% and 12%); cisapride 0.1 μM increased APD90 to 176.2%; and tetrodotoxin 10 μM decreased maximum slope of phase to 33.3% of control, peak depolarization potential to 76.3% of control, and shortened APD90 on average to 80.4%. These results prove feasibility of automated voltage- and current-clamp recordings on human iPSC-CM and their potential use for in-depth drug evaluation and proarrhythmic liability assessment, as well as for diagnosis and pharmacology tests for cardiac channelopathy patients. PMID:25353059

  15. Amplitude equation approach to spatiotemporal dynamics of cardiac alternans

    NASA Astrophysics Data System (ADS)

    Echebarria, Blas; Karma, Alain

    2007-11-01

    Amplitude equations are derived that describe the spatiotemporal dynamics of cardiac alternans during periodic pacing of one- [B. Echebarria and A. Karma, Phys. Rev. Lett. 88, 208101 (2002)] and two-dimensional homogeneous tissue and one-dimensional anatomical reentry in a ring of homogeneous tissue. These equations provide a simple physical understanding of arrhythmogenic patterns of period-doubling oscillations of action potential duration with a spatially varying phase and amplitude, as well as explicit quantitative predictions that can be compared to ionic model simulations or experiments. The form of the equations is expected to be valid for a large class of ionic models but the coefficients are derived analytically only for a two-variable ionic model and calculated numerically for the original Noble model of Purkinje fiber action potential. In paced tissue, this theory explains the formation of “spatially discordant alternans” by a linear instability mechanism that produces a periodic pattern of out-of-phase domains of alternans. The wavelength of this pattern, equal to twice the spacing between nodes separating out-of-phase domains, is shown to depend on three fundamental length scales that are determined by the strength of cell-to-cell coupling and conduction velocity (CV) restitution. Moreover, the patterns of alternans can be either stationary, with fixed nodes, or traveling, with moving nodes and hence quasiperiodic oscillations of action potential duration, depending on the relative strength of the destabilizing effect of CV restitution and the stabilizing effect of diffusive coupling. For the ring geometry, we recover the results of Courtemanche, Glass, and Keener [Phys. Rev. Lett. 70, 2182 (1993)] with two important modifications due to cell-to-cell diffusive coupling. First, this coupling breaks the degeneracy of an infinite-dimensional Hopf bifurcation such that the most unstable mode of alternans corresponds to the longest quantized wavelength

  16. Amplitude equation approach to spatiotemporal dynamics of cardiac alternans.

    PubMed

    Echebarria, Blas; Karma, Alain

    2007-11-01

    Amplitude equations are derived that describe the spatiotemporal dynamics of cardiac alternans during periodic pacing of one- [B. Echebarria and A. Karma, Phys. Rev. Lett. 88, 208101 (2002)] and two-dimensional homogeneous tissue and one-dimensional anatomical reentry in a ring of homogeneous tissue. These equations provide a simple physical understanding of arrhythmogenic patterns of period-doubling oscillations of action potential duration with a spatially varying phase and amplitude, as well as explicit quantitative predictions that can be compared to ionic model simulations or experiments. The form of the equations is expected to be valid for a large class of ionic models but the coefficients are derived analytically only for a two-variable ionic model and calculated numerically for the original Noble model of Purkinje fiber action potential. In paced tissue, this theory explains the formation of "spatially discordant alternans" by a linear instability mechanism that produces a periodic pattern of out-of-phase domains of alternans. The wavelength of this pattern, equal to twice the spacing between nodes separating out-of-phase domains, is shown to depend on three fundamental length scales that are determined by the strength of cell-to-cell coupling and conduction velocity (CV) restitution. Moreover, the patterns of alternans can be either stationary, with fixed nodes, or traveling, with moving nodes and hence quasiperiodic oscillations of action potential duration, depending on the relative strength of the destabilizing effect of CV restitution and the stabilizing effect of diffusive coupling. For the ring geometry, we recover the results of Courtemanche, Glass, and Keener [Phys. Rev. Lett. 70, 2182 (1993)] with two important modifications due to cell-to-cell diffusive coupling. First, this coupling breaks the degeneracy of an infinite-dimensional Hopf bifurcation such that the most unstable mode of alternans corresponds to the longest quantized wavelength of

  17. Model selection for amplitude analysis

    NASA Astrophysics Data System (ADS)

    Guegan, B.; Hardin, J.; Stevens, J.; Williams, M.

    2015-09-01

    Model complexity in amplitude analyses is often a priori under-constrained since the underlying theory permits a large number of possible amplitudes to contribute to most physical processes. The use of an overly complex model results in reduced predictive power and worse resolution on unknown parameters of interest. Therefore, it is common to reduce the complexity by removing from consideration some subset of the allowed amplitudes. This paper studies a method for limiting model complexity from the data sample itself through regularization during regression in the context of a multivariate (Dalitz-plot) analysis. The regularization technique applied greatly improves the performance. An outline of how to obtain the significance of a resonance in a multivariate amplitude analysis is also provided.

  18. Spurious cross-frequency amplitude-amplitude coupling in nonstationary, nonlinear signals

    NASA Astrophysics Data System (ADS)

    Yeh, Chien-Hung; Lo, Men-Tzung; Hu, Kun

    2016-07-01

    Recent studies of brain activities show that cross-frequency coupling (CFC) plays an important role in memory and learning. Many measures have been proposed to investigate the CFC phenomenon, including the correlation between the amplitude envelopes of two brain waves at different frequencies - cross-frequency amplitude-amplitude coupling (AAC). In this short communication, we describe how nonstationary, nonlinear oscillatory signals may produce spurious cross-frequency AAC. Utilizing the empirical mode decomposition, we also propose a new method for assessment of AAC that can potentially reduce the effects of nonlinearity and nonstationarity and, thus, help to avoid the detection of artificial AACs. We compare the performances of this new method and the traditional Fourier-based AAC method. We also discuss the strategies to identify potential spurious AACs.

  19. Positive amplitudes in the amplituhedron

    NASA Astrophysics Data System (ADS)

    Arkani-Hamed, Nima; Hodges, Andrew; Trnka, Jaroslav

    2015-08-01

    The all-loop integrand for scattering amplitudes in planar SYM is determined by an "amplitude form" with logarithmic singularities on the boundary of the amplituhedron. In this note we provide strong evidence for a new striking property of the superamplitude, which we conjecture to be true to all loop orders: the amplitude form is positive when evaluated inside the amplituhedron. The statement is sensibly formulated thanks to the natural "bosonization" of the superamplitude associated with the amplituhedron geometry. However this positivity is not manifest in any of the current approaches to scattering amplitudes, and in particular not in the cellulations of the amplituhedron related to on-shell diagrams and the positive grassmannian. The surprising positivity of the form suggests the existence of a "dual amplituhedron" formulation where this feature would be made obvious. We also suggest that the positivity is associated with an extended picture of amplituhedron geometry, with the amplituhedron sitting inside a co-dimension one surface separating "legal" and "illegal" local singularities of the amplitude. We illustrate this in several simple examples, obtaining new expressions for amplitudes not associated with any triangulations, but following in a more invariant manner from a global view of the positive geometry.

  20. Tempo and amplitude in growth.

    PubMed

    Hermanussen, Michael

    2011-01-01

    Growth is defined as an increase of size over time with time usually defined as physical time. Yet, the rigid metric of physical time is not directly relevant to the internal dynamics of growth. Growth is linked to maturation. Children and adolescents differ in the tempo at which they mature. One calendar year differs in its meaning in a fast maturing, and in a slow maturing child. The slow child needs more calendar years for completing the same stage of maturity. Many characteristics in the human growth curve are tempo characteristics. Tempo - being fast or slow maturing - has to be carefully separated from amplitude - being tall or short. Several characteristic phenomena such as catch-up growth after periods of illness and starvation are largely tempo phenomena, and do usually not affect the amplitude component of growth. Applying Functional Data Analysis and Principal Component Analysis, the two main sources of height variance: tempo and amplitude can statistically be separate and quantified. Tempo appears to be more sensitive than amplitude to nutrition, health and environmental stress. An appropriate analysis of growth requires disentangling its two major components: amplitude and tempo. The assessment of the developmental tempo thus is an integral part of assessing child and adolescent growth. Though an Internet portal is currently available to process small amounts of height data (www.willi-will-wachsen.com) for separately determining amplitude and tempo in growth, there is urgent need of better and practical solutions for analyzing individual growth.

  1. DCT domain feature extraction scheme based on motor unit action potential of EMG signal for neuromuscular disease classification.

    PubMed

    Doulah, Abul Barkat Mollah Sayeed Ud; Fattah, Shaikh Anowarul; Zhu, Wei-Ping; Ahmad, M Omair

    2014-01-01

    A feature extraction scheme based on discrete cosine transform (DCT) of electromyography (EMG) signals is proposed for the classification of normal event and a neuromuscular disease, namely the amyotrophic lateral sclerosis. Instead of employing DCT directly on EMG data, it is employed on the motor unit action potentials (MUAPs) extracted from the EMG signal via a template matching-based decomposition technique. Unlike conventional MUAP-based methods, only one MUAP with maximum dynamic range is selected for DCT-based feature extraction. Magnitude and frequency values of a few high-energy DCT coefficients corresponding to the selected MUAP are used as the desired feature which not only reduces computational burden, but also offers better feature quality with high within-class compactness and between-class separation. For the purpose of classification, the K-nearest neighbourhood classifier is employed. Extensive analysis is performed on clinical EMG database and it is found that the proposed method provides a very satisfactory performance in terms of specificity, sensitivity and overall classification accuracy.

  2. Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods

    PubMed Central

    Daly, Aidan C.; Holmes, Chris

    2015-01-01

    As cardiac cell models become increasingly complex, a correspondingly complex ‘genealogy’ of inherited parameter values has also emerged. The result has been the loss of a direct link between model parameters and experimental data, limiting both reproducibility and the ability to re-fit to new data. We examine the ability of approximate Bayesian computation (ABC) to infer parameter distributions in the seminal action potential model of Hodgkin and Huxley, for which an immediate and documented connection to experimental results exists. The ability of ABC to produce tight posteriors around the reported values for the gating rates of sodium and potassium ion channels validates the precision of this early work, while the highly variable posteriors around certain voltage dependency parameters suggests that voltage clamp experiments alone are insufficient to constrain the full model. Despite this, Hodgkin and Huxley's estimates are shown to be competitive with those produced by ABC, and the variable behaviour of posterior parametrized models under complex voltage protocols suggests that with additional data the model could be fully constrained. This work will provide the starting point for a full identifiability analysis of commonly used cardiac models, as well as a template for informative, data-driven parametrization of newly proposed models. PMID:27019736

  3. Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics

    PubMed Central

    Goytia, Maira M.; Donnelly, Paul S.; Shafer, William M.

    2015-01-01

    There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria gonorrhoeae showed that Cu(btsc) complexes may act as inhibitors of respiratory dehydrogenases in the electron transport chain. We now show that these complexes are also toxic against pathogens that lack a respiratory chain. Respiration in Escherichia coli was slightly affected by Cu(btsc) complexes, but our results indicate that, in this model bacterium, the complexes act primarily as agents that deliver toxic Cu ions efficiently into the cytoplasm. Although the chemistry of Cu(btsc) complexes may dictate their mechanism of action, their efficacy depends heavily on bacterial physiology. This is linked to the ability of the target bacterium to tolerate Cu and, additionally, the susceptibility of the respiratory chain to direct inhibition by Cu(btsc) complexes. The physiology of N. gonorrhoeae, including multidrug-resistant strains, makes it highly susceptible to damage by Cu ions and Cu(btsc) complexes, highlighting the potential of Cu(btsc) complexes (and Cu-based therapeutics) as a promising treatment against this important bacterial pathogen. PMID:26239980

  4. Liénard-type models for the simulation of the action potential of cardiac nodal cells

    NASA Astrophysics Data System (ADS)

    Podziemski, P.; Żebrowski, J. J.

    2013-10-01

    Existing models of cardiac cells which include multi-variable cardiac transmembrane current are too complex to simulate the long time dynamical properties of the heart rhythm. The large number of parameters that need to be defined and set for such models make them not only cumbersome to use but also require a large computing power. Consequently, the application of such models for the bedside analysis of heart rate of a specific patient may be difficult. Other ways of modelling need to be investigated. We consider the general problem of developing a model of cardiac pacemaker tissue that allows to combine the investigation of phenomena at a time scale of thousands of heart beats with the ability to reproduce realistic tissue-level characteristics of cell dynamics. We propose a modified van der Pol-Duffing equation-a Liénard-type oscillator-as a phenomenological model for cardiac nodal tissue, with certain important physiological similarities to ion-channel models of cardiac pacemaker cells. The model presented here is specifically designed to qualitatively reproduce mesoscopic characteristics of cell dynamics, including action potential duration (APD) restitution properties, phase response characteristics, and phase space structure. We show that these characteristics agree qualitatively with the extensive ionic models and experimental results in the literature [Anumonwo et al., 1991, [33], Cao et al., 1999, [49], Coster and Celler, 2003, [31], Qu, 2004, [45], Tsalikakis et al., 2007, [32], Inada et al., 2009, [14], Qu et al., 2010, [50

  5. Novel cinnamic acid/4-aminoquinoline conjugates bearing non-proteinogenic amino acids: towards the development of potential dual action antimalarials.

    PubMed

    Pérez, Bianca C; Teixeira, Cátia; Figueiras, Marta; Gut, Jiri; Rosenthal, Philip J; Gomes, José R B; Gomes, Paula

    2012-08-01

    A series of cinnamic acid/4-aminoquinoline conjugates conceived to link, through a proper retro-enantio dipeptide, a heterocyclic core known to prevent hemozoin formation, to a trans-cinnamic acid motif capable of inhibiting enzyme catalytic Cys residues, were synthesized as potential dual-action antimalarials. The effect of amino acid configuration and the absence of the dipeptide spacer were also assessed. The replacement of the D-amino acids by their natural L counterparts led to a decrease in both anti-plasmodial and falcipain-inhibitory activity, suggesting that the former are preferable. Molecules with such spacer were active against blood-stage Plasmodium falciparum, in vitro, and hemozoin formation, implying that the dipeptide has a key role in mediating these two activities. In turn, compounds without spacer were better falcipain-2 inhibitors, likely because these compounds are smaller and have their vinyl bonds in closer vicinity to the catalytic Cys, as suggested by molecular modeling calculations. These novel conjugates constitute promising leads for the development of new antiplasmodials targeted at blood-stage malaria parasites.

  6. DCT domain feature extraction scheme based on motor unit action potential of EMG signal for neuromuscular disease classification

    PubMed Central

    Doulah, Abul Barkat Mollah Sayeed Ud; Zhu, Wei-Ping; Ahmad, M. Omair

    2014-01-01

    A feature extraction scheme based on discrete cosine transform (DCT) of electromyography (EMG) signals is proposed for the classification of normal event and a neuromuscular disease, namely the amyotrophic lateral sclerosis. Instead of employing DCT directly on EMG data, it is employed on the motor unit action potentials (MUAPs) extracted from the EMG signal via a template matching-based decomposition technique. Unlike conventional MUAP-based methods, only one MUAP with maximum dynamic range is selected for DCT-based feature extraction. Magnitude and frequency values of a few high-energy DCT coefficients corresponding to the selected MUAP are used as the desired feature which not only reduces computational burden, but also offers better feature quality with high within-class compactness and between-class separation. For the purpose of classification, the K-nearest neighbourhood classifier is employed. Extensive analysis is performed on clinical EMG database and it is found that the proposed method provides a very satisfactory performance in terms of specificity, sensitivity and overall classification accuracy. PMID:26609372

  7. Electrophysiological evaluation of nerve function in inferior alveolar nerve injury: relationship between nerve action potentials and histomorphometric observations.

    PubMed

    Murayama, M; Sasaki, K; Shibahara, T

    2015-12-01

    The objective of this study was to improve the accuracy of diagnosis of inferior alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the sensory nerve action potential (SNAP) and sensory nerve conduction velocity (SCV). Crush and partial and complete nerve amputation injuries were applied to the IAN of rabbits, then SNAPs and histomorphometric observations were recorded at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at 5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an increase at week 10. For partial nerve amputation, small to medium-sized nerve fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10. Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable from week 10, however the SCV was extremely low. This study showed SCV to be an effective factor in the evaluation of nerve injury and regeneration. PMID:26433750

  8. Anticancer potential and mechanism of action of mango ginger (Curcuma amada Roxb.) supercritical CO₂ extract in human glioblastoma cells.

    PubMed

    Ramachandran, Cheppail; Lollett, Ivonne V; Escalon, Enrique; Quirin, Karl-Werner; Melnick, Steven J

    2015-04-01

    Mango ginger (Curcuma amada Roxb.) is among the less-investigated species of Curcuma for anticancer properties. We have investigated the anticancer potential and the mechanism of action of a supercritical CO2 extract of mango ginger (CA) in the U-87MG human glioblastoma cell line. CA demonstrated higher cytotoxicity than temozolomide, etoposide, curcumin, and turmeric force with IC50, IC75, and IC90 values of 4.92 μg/mL, 12.87 μg/mL, and 21.30 μg/mL, respectively. Inhibitory concentration values of CA for normal embryonic mouse hypothalamus cell line (mHypoE-N1) is significantly higher than glioblastoma cell line, indicating the specificity of CA against brain tumor cells. CompuSyn analysis indicates that CA acts synergistically with temozolomide and etoposide for the cytotoxicity with combination index values of <1. CA treatment also induces apoptosis in glioblastoma cells in a dose-dependent manner and downregulates genes associated with apoptosis, cell proliferation, telomerase activity, oncogenesis, and drug resistance in glioblastoma cells.