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Sample records for action potential dynamics

  1. A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.

    PubMed

    Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

    2008-01-15

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.

  2. A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

    PubMed Central

    Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G.; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N.

    2008-01-01

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Cai) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (ICa,L) and Cai cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35–37°C. Incorporating a minimal seven-state Markovian model of ICa,L that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Cai cycling model, the new model replicates experimentally observed action potential duration and Cai transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing. PMID:18160660

  3. 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

  4. Nonlinear Dynamic Modeling of Neuron Action Potential Threshold During Synaptically Driven Broadband Intracellular Activity

    PubMed Central

    Roach, Shane M.; Song, Dong; Berger, Theodore W.

    2012-01-01

    Activity-dependent variation of neuronal thresholds for action potential (AP) generation is one of the key determinants of spike-train temporal-pattern transformations from presynaptic to postsynaptic spike trains. In this study, we model the nonlinear dynamics of the threshold variation during synaptically driven broadband intracellular activity. First, membrane potentials of single CA1 pyramidal cells were recorded under physiologically plausible broadband stimulation conditions. Second, a method was developed to measure AP thresholds from the continuous recordings of membrane potentials. It involves measuring the turning points of APs by analyzing the third-order derivatives of the membrane potentials. Four stimulation paradigms with different temporal patterns were applied to validate this method by comparing the measured AP turning points and the actual AP thresholds estimated with varying stimulation intensities. Results show that the AP turning points provide consistent measurement of the AP thresholds, except for a constant offset. It indicates that 1) the variation of AP turning points represents the nonlinearities of threshold dynamics; and 2) an optimization of the constant offset is required to achieve accurate spike prediction. Third, a nonlinear dynamical third-order Volterra model was built to describe the relations between the threshold dynamics and the AP activities. Results show that the model can predict threshold accurately based on the preceding APs. Finally, the dynamic threshold model was integrated into a previously developed single neuron model and resulted in a 33% improvement in spike prediction. PMID:22156947

  5. Dependence of transient and residual calcium dynamics on action-potential patterning during neuropeptide secretion.

    PubMed

    Muschol, M; Salzberg, B M

    2000-09-15

    Secretion of the neuropeptide arginine vasopressin (AVP) from the neurohypophysis is optimized by short phasic bursts of action potentials with a mean intraburst frequency around 10 Hz. Several hypotheses, most prominently action-potential broadening and buildup of residual calcium, have been proposed to explain this frequency dependence of AVP release. However, how either of these mechanisms would optimize release at any given frequency remains an open question. We have addressed this issue by correlating the frequency-dependence of intraterminal calcium dynamics and AVP release during action-potential stimulation. By monitoring the intraterminal calcium changes with low-affinity indicator dyes and millisecond time resolution, the signal could be dissected into three separate components: rapid Ca(2+) rises (Delta[Ca(2+)](tr)) related to action-potential depolarization, Ca(2+) extrusion and/or uptake, and a gradual increase in residual calcium (Delta[Ca(2+)](res)) throughout the stimulus train. Action-potential stimulation modulated all three components in a manner dependent on both the stimulation frequency and number of stimuli. Overall, the cumulative Delta[Ca(2+)](tr) amplitude initially increased with f(Stim) and then rapidly deteriorated, with a maximum around f(Stim)

  6. The real-time link between person perception and action: brain potential evidence for dynamic continuity.

    PubMed

    Freeman, Jonathan B; Ambady, Nalini; Midgley, Katherine J; Holcomb, Phillip J

    2011-01-01

    Using event-related potentials, we investigated how the brain extracts information from another's face and translates it into relevant action in real time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250 and 550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target's sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another's face before perceivers have finished interpreting what they just saw.

  7. The real-time link between person perception and action: Brain potential evidence for dynamic continuity

    PubMed Central

    Freeman, Jonathan B.; Ambady, Nalini; Midgley, Katherine J.; Holcomb, Phillip J.

    2010-01-01

    Using event-related potentials, we investigated how the brain extracts information from another’s face and translates it into relevant action in real-time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250-550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential (LRP) revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target’s sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another’s face before perceivers have finished interpreting what they just saw. PMID:20602284

  8. Applications of control theory to the dynamics and propagation of cardiac action potentials.

    PubMed

    Muñoz, Laura M; Stockton, Jonathan F; Otani, Niels F

    2010-09-01

    Sudden cardiac arrest is a widespread cause of death in the industrialized world. Most cases of sudden cardiac arrest are due to ventricular fibrillation (VF), a lethal cardiac arrhythmia. Electrophysiological abnormalities such as alternans (a beat-to-beat alternation in action potential duration) and conduction block have been suspected to contribute to the onset of VF. This study focuses on the use of control-systems techniques to analyze and design methods for suppressing these precursor factors. Control-systems tools, specifically controllability analysis and Lyapunov stability methods, were applied to a two-variable Karma model of the action-potential (AP) dynamics of a single cell, to analyze the effectiveness of strategies for suppressing AP abnormalities. State-feedback-integral (SFI) control was then applied to a Purkinje fiber simulated with the Karma model, where only one stimulating electrode was used to affect the system. SFI control converted both discordant alternans and 2:1 conduction block back toward more normal patterns, over a wider range of fiber lengths and pacing intervals compared with a Pyragas-type chaos controller. The advantages conferred by using feedback from multiple locations in the fiber, and using integral (i.e., memory) terms in the controller, are discussed.

  9. Applications of Control Theory to the Dynamics and Propagation of Cardiac Action Potentials

    PubMed Central

    Muñoz, Laura M.; Stockton, Jonathan F.; Otani, Niels F.

    2011-01-01

    Sudden cardiac arrest is a widespread cause of death in the industrialized world. Most cases of sudden cardiac arrest are due to ventricular fibrillation (VF), a lethal cardiac arrhythmia. Electrophysiological abnormalities such as alternans (a beat-to-beat alternation in action potential duration) and conduction block have been suspected to contribute to the onset of VF. This study focuses on the use of control-systems techniques to analyze and design methods for suppressing these precursor factors. Control-systems tools, specifically controllability analysis and Lyapunov stability methods, were applied to a two-variable Karma model of the action-potential (AP) dynamics of a single cell, to analyze the effectiveness of strategies for suppressing AP abnormalities. State-feedback-integral (SFI) control was then applied to a Purkinje fiber simulated with the Karma model, where only one stimulating electrode was used to affect the system. SFI control converted both discordant alternans and 2:1 conduction block back toward more normal patterns, over a wider range of fiber lengths and pacing intervals compared with a Pyragas-type chaos controller. The advantages conferred by using feedback from multiple locations in the fiber, and using integral (i.e., memory) terms in the controller, are discussed. PMID:20407833

  10. 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.

  11. The Mechanisms of Calcium Cycling and Action Potential Dynamics in Cardiac Alternans

    PubMed Central

    Kanaporis, Giedrius; Blatter, Lothar A.

    2015-01-01

    Rationale Alternans is a risk factor for cardiac arrhythmia, including atrial fibrillation. At the cellular level alternans manifests as beat-to-beat alternations in contraction, action potential duration (APD) and magnitude of the Ca2+ transient (CaT). Electromechanical and CaT alternans are highly correlated, however it has remained controversial whether the primary cause of alternans is a disturbance of cellular Ca2+ signaling or electrical membrane properties. Objective Determine whether a primary failure of intracellular Ca2+ regulation or disturbances in Vm and AP regulation are responsible for the occurrence of alternans in atrial myocytes. Methods and Results Pacing-induced APD and CaT alternans were studied in single rabbit atrial and ventricular myocytes using combined [Ca2+]i and electrophysiological measurements. In current-clamp experiments APD and CaT alternans strongly correlated in time and magnitude. CaT alternans was observed without alternation in L-type Ca2+ current, however, elimination of intracellular Ca2+ release abolished APD alternans, indicating that [Ca2+]i dynamics have a profound effect on the occurrence of CaT alternans. Trains of two distinctive voltage commands in form of APs recorded during large and small alternans CaTs, were applied to voltage-clamped cells. CaT alternans were observed with and without alternation in the voltage command shape. During ‘alternans AP-clamp’ large CaTs coincided with both long and short AP waveforms, indicating that CaT alternans develop irrespective of AP dynamics. Conclusion The primary mechanism underlying alternans in atrial cells, similarly to ventricular cells, resides in a disturbance of Ca2+ signaling while APD alternans are a secondary consequence, mediated by Ca2+-dependent AP modulation. PMID:25532796

  12. Dynamics of the late Na(+) current during cardiac action potential and its contribution to afterdepolarizations.

    PubMed

    Horvath, Balazs; Banyasz, Tamas; Jian, Zhong; Hegyi, Bence; Kistamas, Kornel; Nanasi, Peter P; Izu, Leighton T; Chen-Izu, Ye

    2013-11-01

    The objective of this work is to examine the contribution of late Na(+) current (INa,L) to the cardiac action potential (AP) and arrhythmogenic activities. In spite of the rapidly growing interest toward this current, there is no publication available on experimental recording of the dynamic INa,L current as it flows during AP with Ca(2+) cycling. Also unknown is how the current profile changes when the Ca(2+)-calmodulin dependent protein kinase II (CaMKII) signaling is altered, and how the current contributes to the development of arrhythmias. In this study we use an innovative AP-clamp Sequential Dissection technique to directly record the INa,L current during the AP with Ca(2+) cycling in the guinea pig ventricular myocytes. First, we found that the magnitude of INa,L measured under AP-clamp is substantially larger than earlier studies indicated. CaMKII inhibition using KN-93 significantly reduced the current. Second, we recorded INa,L together with IKs, IKr, and IK1 in the same cell to understand how these currents counterbalance to shape the AP morphology. We found that the amplitude and the total charge carried by INa,L exceed that of IKs. Third, facilitation of INa,L by Anemone toxin II prolonged APD and induced Ca(2+) oscillations that led to early and delayed afterdepolarizations and triggered APs; these arrhythmogenic activities were eliminated by buffering Ca(2+) with BAPTA. In conclusion, INa,L contributes a significantly large inward current that prolongs APD and unbalances the Ca(2+) homeostasis to cause arrhythmogenic APs.

  13. Dynamics of the Late Na+ current during cardiac action potential and its contribution to afterdepolarizations

    PubMed Central

    Horvath, Balazs; Banyasz, Tamas; Jian, Zhong; Hegyi, Bence; Kistamas, Kornel; Nanasi, Peter P.; Izu, Leighton T.; Chen-Izu, Ye

    2013-01-01

    The objective of this work is to examine the contribution of late Na+ current (INa,L) to the cardiac action potential (AP) and arrhythmogenic activities. In spite of the rapidly growing interest toward this current, there is no publication available on experimental recording of the dynamic INa,L current as it flows during AP with Ca2+ cycling. Also unknown is how the current profile changes when the Ca2+-calmodulin dependent protein kinase II (CaMKII) signaling is altered, and how the current contributes to the development of arrhythmias. In this study we use an innovative AP-clamp Sequential Dissection technique to directly record the INa,L current during the AP with Ca2+ cycling in the guinea pig ventricular myocytes. First, we found that the magnitude of INa,L measured under AP-clamp is substantially larger than earlier studies indicated. CaMKII inhibition using KN-93 significantly reduced the current. Second, we recorded INa,L together with IKs, IKr, and IK1 in the same cell to understand how these currents counterbalance to shape the AP morphology. We found that the amplitude and the total charge carried by INa,L exceed that of IKs. Third, facilitation of INa,L by Anemone toxin II prolonged APD and induced Ca2+ oscillations that led to early and delayed afterdepolarizations and triggered APs; these arrhythmogenic activities were eliminated by buffering Ca2+ with BAPTA. In conclusion, INa,L contributes a significantly large inward current that prolongs APD and unbalances the Ca2+ homeostasis to cause arrhythmogenic APs. PMID:24012538

  14. 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.

  15. Cycle length restitution in sinoatrial node cells: a theory for understanding spontaneous action potential dynamics.

    PubMed

    Glynn, Patric; Onal, Birce; Hund, Thomas J

    2014-01-01

    Normal heart rhythm (sinus rhythm) is governed by the sinoatrial node, a specialized and highly heterogeneous collection of spontaneously active myocytes in the right atrium. Sinoatrial node dysfunction, characterized by slow and/or asynchronous pacemaker activity and even failure, is associated with cardiovascular disease (e.g. heart failure, atrial fibrillation). While tremendous progress has been made in understanding the molecular and ionic basis of automaticity in sinoatrial node cells, the dynamics governing sinoatrial nodel cell synchrony and overall pacemaker function remain unclear. Here, a well-validated computational model of the mouse sinoatrial node cell is used to test the hypothesis that sinoatrial node cell dynamics reflect an inherent restitution property (cycle length restitution) that may give rise to a wide range of behavior from regular periodicity to highly complex, irregular activation. Computer simulations are performed to determine the cycle length restitution curve in the computational model using a newly defined voltage pulse protocol. The ability of the restitution curve to predict sinoatrial node cell dynamics (e.g., the emergence of irregular spontaneous activity) and susceptibility to termination is evaluated. Finally, ionic and tissue level factors (e.g. ion channel conductances, ion concentrations, cell-to-cell coupling) that influence restitution and sinoatrial node cell dynamics are explored. Together, these findings suggest that cycle length restitution may be a useful tool for analyzing cell dynamics and dysfunction in the sinoatrial node.

  16. An action potential-driven model of soleus muscle activation dynamics for locomotor-like movements

    PubMed Central

    Kim, Hojeong; Sandercock, Thomas G.; Heckman, C. J.

    2016-01-01

    Objective The goal of this study was to develop a physiologically plausible, computationally robust model for the muscle activation dynamics (A(t)) under physiologically relevant excitation and movement. Approach The interaction of excitation and movement on A(t) was investigated comparing the force production between a cat soleus muscle and its Hill-type model. For capturing A(t) under excitation and movement variation, a modular modeling framework was proposed comprising of 3 compartments: (1) spikes-to-[Ca2+]; (2) [Ca2+]-to-A; and (3) A-to-force transformation. The individual signal transformations were modeled based on physiological factors so that the parameter values could be separately determined for individual modules directly based on experimental data. Main results The strong dependency of A(t) on excitation frequency and muscle length was found during both isometric and dynamically-moving contractions. The identified dependencies of A(t) under the static and dynamic conditions could be incorporated in the modular modeling framework by modulating the model parameters as a function of movement input. The new modeling approach was also applicable to cat soleus muscles producing waveforms independent of those used to set the model parameters. Significance This study provides a modeling framework for spike-driven muscle responses during movement, that is suitable not only for insights into molecular mechanisms underlying muscle behaviors but also for large scale simulations. PMID:26087477

  17. An action potential-driven model of soleus muscle activation dynamics for locomotor-like movements

    NASA Astrophysics Data System (ADS)

    Kim, Hojeong; Sandercock, Thomas G.; Heckman, C. J.

    2015-08-01

    Objective. The goal of this study was to develop a physiologically plausible, computationally robust model for muscle activation dynamics (A(t)) under physiologically relevant excitation and movement. Approach. The interaction of excitation and movement on A(t) was investigated comparing the force production between a cat soleus muscle and its Hill-type model. For capturing A(t) under excitation and movement variation, a modular modeling framework was proposed comprising of three compartments: (1) spikes-to-[Ca2+]; (2) [Ca2+]-to-A; and (3) A-to-force transformation. The individual signal transformations were modeled based on physiological factors so that the parameter values could be separately determined for individual modules directly based on experimental data. Main results. The strong dependency of A(t) on excitation frequency and muscle length was found during both isometric and dynamically-moving contractions. The identified dependencies of A(t) under the static and dynamic conditions could be incorporated in the modular modeling framework by modulating the model parameters as a function of movement input. The new modeling approach was also applicable to cat soleus muscles producing waveforms independent of those used to set the model parameters. Significance. This study provides a modeling framework for spike-driven muscle responses during movement, that is suitable not only for insights into molecular mechanisms underlying muscle behaviors but also for large scale simulations.

  18. Optogenetics-enabled dynamic modulation of action potential duration in atrial tissue: feasibility of a novel therapeutic approach

    PubMed Central

    Karathanos, Thomas V.; Boyle, Patrick M.; Trayanova, Natalia A.

    2014-01-01

    Aims Diseases that abbreviate the cardiac action potential (AP) by increasing the strength of repolarizing transmembrane currents are highly arrhythmogenic. It has been proposed that optogenetic tools could be used to restore normal AP duration (APD) in the heart under such disease conditions. This study aims to evaluate the efficacy of an optogenetic treatment modality for prolonging pathologically shortened APs in a detailed computational model of short QT syndrome (SQTS) in the human atria, and compare it to drug treatment. Methods and results We used a human atrial myocyte model with faster repolarization caused by SQTS; light sensitivity was inscribed via the presence of channelrhodopsin-2 (ChR2). We conducted simulations in single cells and in a magnetic resonance imaging-based model of the human left atrium (LA). Application of an appropriate optical stimulus to a diseased cell dynamically increased APD, producing an excellent match to control AP (<1.5 mV deviation); treatment of a diseased cell with an AP-prolonging drug (chloroquine) also increased APD, but the match to control AP was worse (>5 mV deviation). Under idealized conditions in the LA (uniform ChR2-expressing cell distribution, no light attenuation), optogenetics-based therapy outperformed chloroquine treatment (APD increased to 87% and 81% of control). However, when non-uniform ChR2-expressing cell distribution and light attenuation were incorporated, optogenetics-based treatment was less effective (APD only increased to 55%). Conclusion This study demonstrates proof of concept for optogenetics-based treatment of diseases that alter atrial AP shape. We identified key practical obstacles intrinsic to the optogenetic approach that must be overcome before such treatments can be realized. PMID:25362173

  19. 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

  20. Repetitive propagation of action potentials destabilizes the structure of the myelin sheath. A dynamic x-ray diffraction study.

    PubMed Central

    Padrón, R; Mateu, L

    1982-01-01

    Time courses of myelin lattice swelling in toad sciatic nerves preexposed to different treatments were determined by x-ray diffraction using a one-dimensional position-sensitive detector. In the nerves supramaximally stimulated for 1 h at 200 Hz, the subsequent process of myelin swelling occurred 45.0 +/- 7.3 min (n = 24) sooner than in resting controls. Sciatic nerves incubated for 1 h in a Ringer's solution deprived of divalent cations (Ca++ and Mg++) exhibited a kinetics of swelling similar to that shown by the stimulated nerves, that is, 52.5 +/- 14.2 min (n = 6) sooner than controls preincubated for the same time in normal Ringer's solution (with divalent cations). The fact that both pretreatments supramaximal stimulation and removal of divalent cations from the perfusion solution produced a similar effect; namely, a decrease of the myelin lattice stability against swelling in distilled water, suggests that the repetitive propagation of action potentials could modify the ionic composition at either the intraperiod channel or the paranodal axoglial junction complexes. PMID:6810970

  1. Acute Alterations of Somatodendritic Action Potential Dynamics in Hippocampal CA1 Pyramidal Cells after Kainate-Induced Status Epilepticus in Mice

    PubMed Central

    Minge, Daniel; Bähring, Robert

    2011-01-01

    Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP) dynamics immediately following status epilepticus (SE) in mice. SE was induced by intraperitoneal (i.p.) injection of kainate, and behavioral manifestation of SE was monitored for 3–4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2–5 mV). No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst) firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP), was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP)-induced Ca2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na+ and K+ current components. PMID:22039527

  2. Segmenting Dynamic Human Action via Statistical Structure

    ERIC Educational Resources Information Center

    Baldwin, Dare; Andersson, Annika; Saffran, Jenny; Meyer, Meredith

    2008-01-01

    Human social, cognitive, and linguistic functioning depends on skills for rapidly processing action. Identifying distinct acts within the dynamic motion flow is one basic component of action processing; for example, skill at segmenting action is foundational to action categorization, verb learning, and comprehension of novel action sequences. Yet…

  3. Potential formulation of sleep dynamics

    NASA Astrophysics Data System (ADS)

    Phillips, A. J. K.; Robinson, P. A.

    2009-02-01

    A physiologically based model of the mechanisms that control the human sleep-wake cycle is formulated in terms of an equivalent nonconservative mechanical potential. The potential is analytically simplified and reduced to a quartic two-well potential, matching the bifurcation structure of the original model. This yields a dynamics-based model that is analytically simpler and has fewer parameters than the original model, allowing easier fitting to experimental data. This model is first demonstrated to semiquantitatively match the dynamics of the physiologically based model from which it is derived, and is then fitted directly to a set of experimentally derived criteria. These criteria place rigorous constraints on the parameter values, and within these constraints the model is shown to reproduce normal sleep-wake dynamics and recovery from sleep deprivation. Furthermore, this approach enables insights into the dynamics by direct analogies to phenomena in well studied mechanical systems. These include the relation between friction in the mechanical system and the timecourse of neurotransmitter action, and the possible relation between stochastic resonance and napping behavior. The model derived here also serves as a platform for future investigations of sleep-wake phenomena from a dynamical perspective.

  4. Simulation of action potential propagation in plants.

    PubMed

    Sukhov, Vladimir; Nerush, Vladimir; Orlova, Lyubov; Vodeneev, Vladimir

    2011-12-21

    Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H(+)-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H(+)-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity.

  5. Imaging action potentials with calcium indicators.

    PubMed

    MacLean, Jason N; Yuste, Rafael

    2009-11-01

    The understanding of neuronal circuits has been, and will continue to be, greatly advanced by the simultaneous imaging of action potentials in neuronal ensembles. This protocol describes "bulk" loading of brain slices with acetoxymethyl (AM) ester calcium indicators in order to monitor action potential activity in large populations of neurons simultaneously. The imaging of calcium influx into neurons provides an indirect, but accurate, measure of action potential generation in individual neurons. Single-cell resolution, and thus the easy identification of every active cell, is the key advantage of the technique.

  6. Cell type-specific and activity-dependent dynamics of action potential-evoked Ca2+ signals in dendrites of hippocampal inhibitory interneurons

    PubMed Central

    Evstratova, Alesya; Chamberland, Simon; Topolnik, Lisa

    2011-01-01

    Abstract In most central neurons, action potentials (APs), generated in the initial axon segment, propagate back into dendrites and trigger considerable Ca2+ entry via activation of voltage-sensitive calcium channels (VSCCs). Despite the similarity in its underlying mechanisms, however, AP-evoked dendritic Ca2+ signalling often demonstrates a cell type-specific profile that is determined by the neuron dendritic properties. Using two-photon Ca2+ imaging in combination with patch-clamp whole-cell recordings, we found that in distinct types of hippocampal inhibitory interneurons Ca2+ transients evoked by backpropagating APs not only were shaped by the interneuron-specific properties of dendritic Ca2+ handling but also involved specific Ca2+ mechanisms that were regulated dynamically by distinct activity patterns. In dendrites of regularly spiking basket cells, AP-evoked Ca2+ rises were of large amplitude and fast kinetics; however, they decreased with membrane hyperpolarization or following high-frequency firing episodes. In contrast, AP-evoked Ca2+ elevations in dendrites of Schaffer collateral-associated cells exhibited significantly smaller amplitude and slower kinetics, but increased with membrane hyperpolarization. These cell type-specific properties of AP-evoked dendritic Ca2+ signalling were determined by distinct endogenous buffer capacities of the interneurons examined and by specific types of VSCCs recruited by APs during different patterns of activity. Furthermore, AP-evoked Ca2+ transients summated efficiently during theta-like bursting and were associated with the induction of long-term potentiation at inhibitory synapses onto both types of interneurons. Therefore, the cell type-specific profile of AP-evoked dendritic Ca2+ signalling is shaped in an activity-dependent manner, such that the same pattern of hippocampal activity can be differentially translated into dendritic Ca2+ signals in different cell types. However, Cell type-specific differences in Ca

  7. Calcium dynamics associated with action potentials in single nerve terminals of pyramidal cells in layer 2/3 of the young rat neocortex

    PubMed Central

    Koester, Helmut J; Sakmann, Bert

    2000-01-01

    Calcium dynamics associated with a single action potential (AP) were studied in single boutons of the axonal arbor of layer 2/3 pyramidal cells in the neocortex of young (P14-16) rats. We used fluorescence imaging with two-photon excitation and Ca2+-selective fluorescence indicators to measure volume-averaged Ca2+ signals. These rapidly reached a peak (in about 1 ms) and then decayed more slowly (tens to hundreds of milliseconds). Single APs and trains of APs reliably evoked Ca2+ transients in en passant boutons located on axon collaterals in cortical layers 2/3, 4 and 5, indicating that APs propagate actively and reliably throughout the axonal arbor. Branch point failures are unlikely to contribute to differences in synaptic efficacy and reliability in the connections made by layer 2/3 pyramidal cells. AP-evoked Ca2+ transients in boutons were mediated by voltage-dependent Ca2+ channels (VDCCs), predominantly by the P/Q- and N-subtypes. Ca2+ transients were, on average, of significantly larger amplitude in boutons than in the flanking segments of the axon collateral. Large amplitude Ca2+ transients in boutons were spatially restricted to within ≤ 3 m of axonal length. Single AP-evoked Ca2+ transients varied up to 10-fold across different boutons even if they were located on the same axon collateral. In contrast, variation of Ca2+ transients evoked by successive APs in a given single bouton was small (coefficient of variation, c.v. ≤ 0.21). Amplitudes of AP-evoked Ca2+ signals did not correlate with the distance of boutons from the soma. In contrast, AP-evoked Ca2+ signals in spines of basal dendrites decreased slightly (correlation coefficient, r2 = -0.27) with distance from the soma. Measurements with the low-affinity Ca2+ indicator Magnesium Green suggest that the volume-averaged residual free [Ca2+]i in a bouton increases on average by 500 nM following a single AP. Higher concentrations of indicator caused, on average, a decrease in the amplitude and an

  8. On quantum potential dynamics

    NASA Astrophysics Data System (ADS)

    Goldstein, Sheldon; Struyve, Ward

    2015-01-01

    Non-relativistic de Broglie-Bohm theory describes particles moving under the guidance of the wave function. In de Broglie's original formulation, the particle dynamics is given by a first-order differential equation. In Bohm's reformulation, it is given by Newton's law of motion with an extra potential that depends on the wave function—the quantum potential—together with a constraint on the possible velocities. It was recently argued, mainly by numerical simulations, that relaxing this velocity constraint leads to a physically untenable theory. We provide further evidence for this by showing that for various wave functions the particles tend to escape the wave packet. In particular, we show that for a central classical potential and bound energy eigenstates the particle motion is often unbounded. This work seems particularly relevant for ways of simulating wave function evolution based on Bohm's formulation of the de Broglie-Bohm theory. Namely, the simulations may become unstable due to deviations from the velocity constraint.

  9. The Dynamics of Perception and Action

    ERIC Educational Resources Information Center

    Warren, William H.

    2006-01-01

    How might one account for the organization in behavior without attributing it to an internal control structure? The present article develops a theoretical framework called behavioral dynamics that integrates an information-based approach to perception with a dynamical systems approach to action. For a given task, the agent and its environment are…

  10. Computer Simulation of the Neuronal Action Potential.

    ERIC Educational Resources Information Center

    Solomon, Paul R.; And Others

    1988-01-01

    A series of computer simulations of the neuronal resting and action potentials are described. Discusses the use of simulations to overcome the difficulties of traditional instruction, such as blackboard illustration, which can only illustrate these events at one point in time. Describes systems requirements necessary to run the simulations.…

  11. 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…

  12. Dopamine gates action potential backpropagation in midbrain dopaminergic neurons.

    PubMed

    Gentet, Luc J; Williams, Stephen R

    2007-02-21

    Dopamine is released from both axonal and somatodendritic sites of midbrain dopaminergic neurons in an action potential-dependent manner. In contrast to the majority of central neurons, the axon of dopaminergic neurons typically originates from a dendritic site, suggesting a specialized computational function. Here, we examine the initiation and spread of action potentials in dopaminergic neurons of the substantia nigra pars reticulata and reveal that the displacement of the axon to a dendritic site allows highly compartmentalized electrical signaling. In response to a train of synaptic input, action potentials initiated at axon-bearing dendritic sites formed a variable trigger for invasion to the soma and contralateral dendritic tree, with action potentials often confined to the axon-bearing dendrite. The application of dopamine increased this form of electrical compartmentalization, an effect mediated by a tonic membrane potential hyperpolarization leading to an increased availability of a class of voltage-dependent potassium channel. These data suggest that the release of dopamine from axonal and somatodendritic sites are dissociable, and that dopamine levels within the midbrain are dynamically controlled by the somatodendritic spread of action potentials.

  13. 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

  14. Decision making and action implementation: evidence for an early visually triggered motor activation specific to potential actions.

    PubMed

    Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

    2013-07-01

    To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential-sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no-go and between-hand choice tasks by transcranial magnetic stimulation of the motor cortex (single- or paired-pulse TMS; 3-ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to-be-produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race-like models with continuous transmission between decision making and action implementation.

  15. Conscious awareness of action potentiates sensorimotor learning.

    PubMed

    Boutin, Arnaud; Blandin, Yannick; Massen, Cristina; Heuer, Herbert; Badets, Arnaud

    2014-10-01

    Many everyday skills are unconsciously learned through repetitions of the same behaviour by binding independent motor acts into unified sets of actions. However, our ability to be consciously aware of producing newly and highly trained motor skills raises the question of the role played by conscious awareness of action upon skill acquisition. In this study we strengthened conscious awareness of self-produced sequential finger movements by way of asking participants to judge their performance in terms of maximal fluency after each trial. Control conditions in which participants did not make any judgment or performance-unrelated judgments were also included. Findings indicate that conscious awareness of action, enhanced via subjective appraisal of motor efficiency, potentiates sensorimotor learning and skilful motor production in optimising the processing and sequencing of action units, as compared to the control groups. The current work lends support to the claim that the learning and skilful expression of sensorimotor behaviours might be grounded upon our ability to be consciously aware of our own motor capability and efficiency.

  16. Stability of Cardiac Action Potential Duration under Periodic Pacing.

    PubMed

    Xiaodong, Han; Hailang, Song; Xiaomei, Wu; Cuiwei, Yang; Zuxiang, Fang

    2005-01-01

    Action potential duration (APD) alternans is believed to be a loss of stability and contributes much to the reentry arrhythmias. The purpose of this study is to analyze the stability conditions for one-dimension model and higher dimension model. These criterions are concluded by linear stability analysis in nonlinear dynamics. They should be useful for finding of cardiac control algorithms in low energy defibrillation and the designing of antiarrhythmic drug.

  17. Support for Dynamic Collaborative Action Teams

    DTIC Science & Technology

    2006-06-01

    Organizations Architecture Experimentation R. Scott Cost Markus E. Dale David P. Glock James Mayfield Christine O. Salamacha David P...Christine N. Salamacha, Michael Cramer, Timothy Frey and David P. Glock , “Dynamic Collaborative Action Teams: Implementing a Transformational Concept

  18. Stochastic actions for diffusive dynamics: reweighting, sampling, and minimization.

    PubMed

    Adib, Artur B

    2008-05-15

    In numerical studies of diffusive dynamics, two different action functionals are often used to specify the probability distribution of trajectories, one of which requires the evaluation of the second derivative of the potential in addition to the force. Here it is argued that both actions are equivalent prescriptions for the purposes of reweighting and sampling trajectories, whereas the most probable path is more generally given by the global minimum of the action involving the second derivative term. The answer to this apparent paradox lies in the nondifferentiable character of Brownian paths, as well as in the "entropy" associated with a given trajectory.

  19. Weber potential from finite velocity of action?

    NASA Astrophysics Data System (ADS)

    Wesley, J. P.

    1992-12-01

    The Weber potential energy U for charges q and q' separated by the distance R is U = (qq'/R)[1 - (dR/dt)2/2c2]. If this potential arises from a finite velocity c of energy transfer Q', where the retarded rate of transfer from q' to q is dQ(t-R/c)/dt = Q'[1 - (dR/dt)/c] and where the advanced rate from q to q' is dQ(t+R/c)/dt = Q'[1 + (dR/dt)/c], then the resultant time-average root-mean-square action is given by{{Q'}}sqrt {1 - {{({{{{{dR}}} {{{dt}}}}} )^2} {{{c}}^{{2}} }}} ≈ {{Q'}}[ {{{1 - }}{{( {{{{{dR}}} {{{dt}}}}} )^2 {{{{dR}}} {{{dt}}}}})^2 {2{{c}}^{{2}} }}}]. Identifying Q' with the Coulomb potential energy qq'/R, the Weber potential is obtained. Using the same argument, Newtonian gravitation yields a corresponding Weber potential energy, qq'/R being replaced by ( - Gmm'/R).

  20. Action-potential modulation during axonal conduction.

    PubMed

    Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji

    2011-02-04

    Once initiated near the soma, an action potential (AP) is thought to propagate autoregeneratively and distribute uniformly over axonal arbors. We challenge this classic view by showing that APs are subject to waveform modulation while they travel down axons. Using fluorescent patch-clamp pipettes, we recorded APs from axon branches of hippocampal CA3 pyramidal neurons ex vivo. The waveforms of axonal APs increased in width in response to the local application of glutamate and an adenosine A(1) receptor antagonist to the axon shafts, but not to other unrelated axon branches. Uncaging of calcium in periaxonal astrocytes caused AP broadening through ionotropic glutamate receptor activation. The broadened APs triggered larger calcium elevations in presynaptic boutons and facilitated synaptic transmission to postsynaptic neurons. This local AP modification may enable axonal computation through the geometry of axon wiring.

  1. Mechanical Surface Waves Accompany Action Potential Propagation

    NASA Astrophysics Data System (ADS)

    Machta, Benjamin; El Hady, Ahmed

    2015-03-01

    The action potential (AP) is the basic mechanism by which information is transmitted along neuronal axons. Although the excitable nature of axons is understood to be primarily electrical, many experimental studies have shown that a mechanical displacement of the axonal membrane co-propagates with the electrical signal. While the experimental evidence for co-propagating mechanical waves is diverse and compelling, there is no consensus for their physical underpinnings. We present a model in which these mechanical displacements arise from the driving of mechanical surface waves, in which potential energy is stored in elastic deformations of the neuronal membrane and cytoskeleton while kinetic energy is stored in the movement of the axoplasmic fluid. In our model these surface waves are driven by the traveling wave of electrical depolarization that characterizes the AP, altering the electrostatic forces across the membrane as it passes. Our model allows us to predict the shape of the displacement that should accompany any traveling wave of voltage, including the well-characterized AP. We expect our model to serve as a framework for understanding the physical origins and possible functional roles of these AWs in neurobiology. See Arxiv/1407.7600

  2. 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

  3. 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.

  4. Action Potential Initiation in Neocortical Inhibitory Interneurons

    PubMed Central

    Li, Tun; Tian, Cuiping; Scalmani, Paolo; Frassoni, Carolina; Mantegazza, Massimo; Wang, Yonghong; Yang, Mingpo; Wu, Si; Shu, Yousheng

    2014-01-01

    Action potential (AP) generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing. However, it remains unclear what determines AP initiation in different interneurons. We focused on two predominant interneuron types in neocortex: parvalbumin (PV)- and somatostatin (SST)-expressing neurons. Patch-clamp recording from mouse prefrontal cortical slices showed that axonal but not somatic Na+ channels exhibit different voltage-dependent properties. The minimal activation voltage of axonal channels in SST was substantially higher (∼7 mV) than in PV cells, consistent with differences in AP thresholds. A more mixed distribution of high- and low-threshold channel subtypes at the axon initial segment (AIS) of SST cells may lead to these differences. Surprisingly, NaV1.2 was found accumulated at AIS of SST but not PV cells; reducing NaV1.2-mediated currents in interneurons promoted recurrent network activity. Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity. PMID:25203314

  5. Action potential broadening in a presynaptic channelopathy.

    PubMed

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

    2016-07-06

    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.

  6. The Temporal Dynamics of Perceiving Other’s Painful Actions

    PubMed Central

    Cui, Fang; Gu, Ruolei; Zhu, Xiangru; Luo, Yue-jia

    2016-01-01

    The present study investigates the temporal dynamics of the brain activity predicting the sensory outcomes of observed hand–object interactions of others. Participants are presented with pictures of a hand grasping or withdrawing from noxious and neutral objects. They are then asked to judge whether this hand–object interaction causes painful consequences. In the early stages of stimulus processing, the effect of action was observed in the event-related potential components N1 and N2. Significant interactions of action × object were observed in the later components P3 and late positive potential (LPP): only when the object was noxious, the action “grasp” elicited a significantly larger amplitude than the action “withdrawal”. These results suggest that: on the one hand, when observing the hand–object interaction from the third-person perspective, the action type of others can be processed in an automatic style. On the other hand, integrating the information of action and object to predict the sensory consequence of this interaction is a top–down, cognitive controlled processing. The current findings are different from previous studies using first-person perspective visual stimuli which support that the processing of hand–object interaction is rapid and automatic. PMID:27920751

  7. Uncertainty Propagation in Nerve Impulses Through the Action Potential Mechanism.

    PubMed

    Torres Valderrama, Aldemar; Witteveen, Jeroen; Navarro, Maria; Blom, Joke

    2015-12-01

    We investigate the propagation of probabilistic uncertainty through the action potential mechanism in nerve cells. Using the Hodgkin-Huxley (H-H) model and Stochastic Collocation on Sparse Grids, we obtain an accurate probabilistic interpretation of the deterministic dynamics of the transmembrane potential and gating variables. Using Sobol indices, out of the 11 uncertain parameters in the H-H model, we unravel two main uncertainty sources, which account for more than 90 % of the fluctuations in neuronal responses, and have a direct biophysical interpretation. We discuss how this interesting feature of the H-H model allows one to reduce greatly the probabilistic degrees of freedom in uncertainty quantification analyses, saving CPU time in numerical simulations and opening possibilities for probabilistic generalisation of other deterministic models of great importance in physiology and mathematical neuroscience.

  8. 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

  9. 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.

  10. Theophylline-induced potentiation of the antinociceptive action of baclofen.

    PubMed

    Sawynok, J

    1983-02-01

    1--Theophylline (35, 50 mg/kg) potentiated the antinociceptive action of intraperitoneally administered baclofen in the tail flick and hot plate tests. Potentiation was most marked when the pretreatment time was 1 h, but some potentiation was still apparent following a 2 h pretreatment. 2--Theophylline alone (50 mg/kg) produced only slight alterations in reaction latency in the two tests. 3--When baclofen was applied directly into the spinal subarachnoid space, a 1 h pretreatment with theophylline produced minimal effects, but a 2 h pretreatment produced an increase in the antinociceptive action of baclofen. 4--These results suggest that theophylline can potentiate the antinociceptive action of baclofen by actions at both supraspinal and spinal sites.

  11. 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

  12. Components of action potential repolarization in cerebellar parallel fibres

    PubMed Central

    Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

    2014-01-01

    Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter. We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K+ channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K+ channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K+ channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties. PMID:25239461

  13. A fast algorithm for estimating actions in triaxial potentials

    NASA Astrophysics Data System (ADS)

    Sanders, Jason L.; Binney, James

    2015-03-01

    We present an approach to approximating rapidly the actions in a general triaxial potential. The method is an extension of the axisymmetric approach presented by Binney, and operates by assuming that the true potential is locally sufficiently close to some Stäckel potential. The choice of Stäckel potential and associated ellipsoidal coordinates is tailored to each individual input phase-space point. We investigate the accuracy of the method when computing actions in a triaxial Navarro-Frenk-White potential. The speed of the algorithm comes at the expense of large errors in the actions, particularly for the box orbits. However, we show that the method can be used to recover the observables of triaxial systems from given distribution functions to sufficient accuracy for the Jeans equations to be satisfied. Consequently, such models could be used to build models of external galaxies as well as triaxial components of our own Galaxy. When more accurate actions are required, this procedure can be combined with torus mapping to produce a fast convergent scheme for action estimation.

  14. Action-Based Dynamical Modelling For The Milky Way Disk

    NASA Astrophysics Data System (ADS)

    Trick, Wilma; Rix, Hans-Walter; Bovy, Jo

    2016-09-01

    We present Road Mapping, a full-likelihood dynamical modelling machinery, that aims to recover the Milky Way's (MW) gravitational potential from large samples of stars in the Galactic disk. Road Mapping models the observed positions and velocities of stars with a parameterized, action-based distribution function (DF) in a parameterized axisymmetric gravitational potential (Binney & McMillan 2011, Binney 2012, Bovy & Rix 2013).In anticipation of the Gaia data release in autumn, we have fully tested Road Mapping and demonstrated its robustness against the breakdown of its assumptions.Using large suites of mock data, we investigated in isolated test cases how the modelling would be affected if the data's true potential or DF was not included in the families of potentials and DFs assumed by Road Mapping, or if we misjudged measurement errors or the spatial selection function (SF) (Trick et al., submitted to ApJ). We found that the potential can be robustly recovered — given the limitations of the assumed potential model—, even for minor misjudgments in DF or SF, or for proper motion errors or distances known to within 10%.We were also able to demonstrate that Road Mapping is still successful if the strong assumption of axisymmetric breaks down (Trick et al., in preparation). Data drawn from a highresolution simulation (D'Onghia et al. 2013) of a MW-like galaxy with pronounced spiral arms does neither follow the assumed simple DF, nor does it come from an axisymmetric potential. We found that as long as the survey volume is large enough, Road Mapping gives good average constraints on the galaxy's potential.We are planning to apply Road Mapping to a real data set — the Tycho-2 catalogue (Hog et al. 2000) —very soon, and might be able to present some preliminary results already at the conference.

  15. Membrane, action, and oscillatory potentials in simulated protocells

    NASA Technical Reports Server (NTRS)

    Syren, R. M.; Fox, S. W.; Przybylski, A. T.; Stratten, W. P.

    1982-01-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KCl) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

  16. Drug-induced changes in action potential duration are proportional to action potential duration in rat ventricular myocardium.

    PubMed

    Bárándi, László; Harmati, Gábor; Horváth, Balázs; Szentandrássy, Norbert; Magyar, János; Varró, András; Nánási, Péter P; Bányász, Tamás

    2010-09-01

    Several cardioactive agents exhibit direct or reverse rate-dependent effects on action potential duration (APD) depending on the experimental conditions. Recently, a new theory has been proposed, suggesting that the reverse rate-dependent mode of drug-action may be a common property of canine, rabbit, guinea pig and human cardiac tissues, and this phenomenon is based on the dependence of drug-action on baseline APD. The aim of the present work was to examine the limitations of this hypothesis by studying the APD lengthening effect of K(+) channel blockers and the APD shortening effect of Ca(2+) channel blockers during the electrical restitution process of rat ventricular action potentials. Rat ventricular muscle was chosen because it has a set of ion currents markedly different from those of other species, its APD is shorter by one order of magnitude than that of the "plateau-forming" larger mammals, and most importantly, its APD increases at higher heart rates - opposite to many other species. The restitution of APD was studied as a function of the diastolic interval, a parameter indicating the proximity of action potentials. It was found that drug-induced APD changes in rat myocardium are proportional with the pre-drug value of APD but not with the diastolic interval, indicating that not the proximity of consecutive action potentials, but the baseline APD itself may determine the magnitude of drug-induced APD changes.

  17. 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.

  18. The impact of synaptic conductance on action potential waveform: evoking realistic action potentials with a simulated synaptic conductance.

    PubMed

    Johnston, Jamie; Postlethwaite, Michael; Forsythe, Ian D

    2009-10-15

    Most current clamp studies trigger action potentials (APs) by step current injection through the recording electrode and assume that the resulting APs are essentially identical to those triggered by orthodromic synaptic inputs. However this assumption is not always valid, particularly when the synaptic conductance is of large magnitude and of close proximity to the axon initial segment. We addressed this question of similarity using the Calyx of Held/MNTB synapse; we compared APs evoked by long duration step current injections, short step current injections and orthodromic synaptic stimuli. Neither injected current protocol evoked APs that matched the evoked orthodromic AP waveform, showing differences in AP height, half-width and after-hyperpolarization. We postulated that this 'error' could arise from changes in the instantaneous conductance during the combined synaptic and AP waveforms, since the driving forces for the respective ionic currents are integrating and continually evolving over this time-course. We demonstrate that a simple Ohm's law manipulation of the EPSC waveform, which accounts for the evolving driving force on the synaptic conductance during the AP, produces waveforms that closely mimic those generated by physiological synaptic stimulation. This stimulation paradigm allows supra-threshold physiological stimulation (single stimuli or trains) without the variability caused by quantal fluctuation in transmitter release, and can be implemented without a specialised dynamic clamp system. Combined with pharmacological tools this method provides a reliable means to assess the physiological roles of postsynaptic ion channels without confounding affects from the presynaptic input.

  19. The perception-action dynamics of action competency are altered by both physical and observational training.

    PubMed

    Buchanan, John J; Ramos, Jorge; Robson, Nina

    2015-04-01

    Action competency is defined as the ability of an individual to self-evaluate their own performance capabilities. The current experiment demonstrated that physical and observational training with a motor skill alters action competency ratings in a similar manner. Using a pre-test and post-test protocol, the results revealed that action competency is constrained prior to training by the intrinsic dynamics of relative phase (ϕ), with in-phase (ϕ = 0°) and anti-phase (ϕ = 180°) patterns receiving higher competency ratings than other relative phase patterns. After 2 days of training, action competency ratings for two trained relative phase patterns, +60° and +120°, increased following physical practice or observational practice. A transfer test revealed that both physical performance ability and action competency ability transferred to the symmetry partners (-60° and -120°) of the two trained relative phase patterns following physical or observational training. The findings also revealed that relative motion direction acts as categorical information that helps to organize action production and facilitate action competency. The results are interpreted based on the coordination dynamics theory of perception-action coupling, and extend this theory by showing that visual perception, action production, and action competency are all constrained in a consistent manner by the dynamics of the order parameter relative phase. As a whole, the findings revealed that relative motion, relative phase, and possibly relative amplitude information are all distinct sources of information that contribute to the emergence of a kinematic understanding of action in the nervous system.

  20. Model-based source localization of extracellular action potentials.

    PubMed

    Somogyvári, Zoltán; Zalányi, László; Ulbert, István; Erdi, Péter

    2005-09-30

    A new model-based analysis method was set up for revealing information encrypted in extracellular spatial potential patterns of neocortical action potentials. Spikes were measured by extracellular linear multiple microelectrode in vivo cat's primary auditory cortex and were analyzed based on current source density (CSD) distribution models. Validity of the monopole and other point source approximations were tested on the measured potential patterns by numerical fitting. We have found, that point source models could not provide accurate description of the measured patterns. We introduced a new model of the CSD distribution on a spiking cell, called counter-current model (CCM). This new model was shown to provide better description of the spatial current distribution of the cell during the initial negative deflection of the extracellular action potential, from the onset of the spike to the negative peak. The new model was tested on simulated extracellular potentials. We proved numerically, that all the parameters of the model could be determined accurately based on measurements. Thus, fitting of the CCM allowed extraction of these parameters from the measurements. Due to model fitting, CSD could be calculated with much higher accuracy as done with the traditional method because distance dependence of the spatial potential patterns was explicitly taken into consideration in our method. Average CSD distribution of the neocortical action potentials was calculated and spatial decay constant of the dendritic trees was determined by applying our new method.

  1. 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.

  2. 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…

  3. 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.

  4. 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…

  5. Temporal dynamics of action perception: differences on ERP evoked by object-related and non-object-related actions.

    PubMed

    Wamain, Yannick; Pluciennicka, Ewa; Kalénine, Solène

    2014-10-01

    While neuropsychological dissociations suggest that distinct processes are involved in execution or perception of transitive (object-related) and intransitive (non-object-related) actions, the few neuroimaging studies that directly contrasted the brain activations underlying transitive and intransitive gesture perception failed to find substantial differences between the two action types. However, the distinction could be visible on brain activity timing within the fronto-parietal network. In this study, we used Event-Related Potential (ERP) method to assess the temporal dynamics of object-related and non-object-related action processing. Although both meaningful, only object-related actions involve object motor features. Accordingly, perception of the two action types would show distinct neural correlates. Participants were presented with four movie types (ORA, Object-Related Action, NORA: Non-Object-Related Action and 2 control movies) and were instructed to perform tasks that required explicit or implicit action recognition (specific action recognition or color change detection). Movies were presented as Point-Light Display (PLD) and thus provided only information about gesture kinematics regardless of action type. ERP were computed during movie visual perception and analyzed as a function of movie type and task. The main result revealed a difference between ORA and NORA on the amplitude of the P3a component in the fronto-parietal region. The difference observed around 250 ms after movie onset do not likely origin from variation in low-level visual features or attention resource allocation. Instead, we suggest that it reflects incidental recruitment of object attributes during object-related action perception. The exact nature of these attributes is discussed.

  6. 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

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

    PubMed

    Bezanilla, F; Rojas, E; Taylor, R E

    1970-12-01

    1. A method for turning a membrane potential control system on and off in less than 10 musec 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.

  8. Ionic currents underlying the action potential of Rana pipiens oocytes.

    PubMed

    Schlichter, L C

    1989-07-01

    Ionic currents in immature, ovulated Rana pipiens oocytes (metaphase I) were studied using the voltage-clamp technique. At this stage of maturity the oocyte can produce action potentials in response to depolarizing current or as an "off response" to hyperpolarizing current. Reducing external Na+ to 1/10 normal (choline substituted) eliminated the action potentials and both the negative-slope region and zero-crossing of the I-V relation. Reducing external Cl- to 1/10 or 1/100 normal (methanesulfonate substituted) lengthened the action potential. The outward current was reduced and a net inward current was revealed. By changing external Na+, Cl-, and K+ concentrations and using blocking agents (SITS, TEA), three voltage- and time-dependent currents were identified, INa, IK and ICl. The Na+ current activated at about 0 mV and reversed at very positive values which decreased during maturation. Inward Na+ current produced the upstroke of the action potential. During each voltage-clamp step the Na+ current activated slowly (seconds) and did not inactivate within many minutes. The Na+ current was not blocked by TTX at micromolar concentrations. The K+ current was present only in the youngest oocytes. Because IK was superimposed on a large leakage current, it appeared to reverse at the resting potential. When leakage currents were subtracted, the reversal potential for IK was more negative than -110 mV in Ringer's solution. IK was outwardly rectifying and strongly activated above -50 mV. The outward K+ current produced an after hyperpolarization at the end of each action potential. IK was blocked completely and reversibly by 20 mM external TEA. The Cl- current activated at about +10 mV and was outwardly rectifying. ICl was blocked completely and reversibly by 400 microM SITS added to the bathing medium. This current helped repolarize the membrane following an action potential in the youngest oocytes and was the only repolarizing current in more mature oocytes that had lost

  9. K+-induced twitch potentiation is not due to longer action potential.

    PubMed

    Yensen, Craig; Matar, Wadih; Renaud, Jean-Marc

    2002-07-01

    The objective of this study was to determine whether an increased duration of the action potential contributes to the K+-induced twitch potentiation at 37 degrees C. Twitch contractions were elicited by field stimulation, and action potentials were measured with conventional microelectrodes. For mouse extensor digitorum longus (EDL) muscle, twitch force was greater at 7-13 mM K+ than at 4.7 mM (control). For soleus muscle, twitch force potentiation was observed between 7 and 11 mM K+. Time to peak and half-relaxation time were not affected by the increase in extracellular K+ concentration in EDL muscle, whereas both parameters became significantly longer in soleus muscle. Decrease in overshoot and prolongation of the action potential duration observed at 9 and 11 mM K+ were mimicked when muscles were respectively exposed to 25 and 50 nM tetrodotoxin (TTX; used to partially block Na+ channels). Despite similar action potentials, twitch force was not potentiated by TTX. It is therefore suggested that the K+-induced potentiation of the twitch in EDL muscle is not due to a prolongation of the action potential and contraction time, whereas a longer contraction, especially the relaxation phase, may contribute to the potentiation in soleus muscle.

  10. 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.

  11. 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

  12. Using extracellular action potential recordings to constrain compartmental models.

    PubMed

    Gold, Carl; Henze, Darrell A; Koch, Christof

    2007-08-01

    We investigate the use of extracellular action potential (EAP) recordings for biophysically faithful compartmental models. We ask whether constraining a model to fit the EAP is superior to matching the intracellular action potential (IAP). In agreement with previous studies, we find that the IAP method under-constrains the parameters. As a result, significantly different sets of parameters can have virtually identical IAP's. In contrast, the EAP method results in a much tighter constraint. We find that the distinguishing characteristics of the waveform--but not its amplitude-resulting from the distribution of active conductances are fairly invariant to changes of electrode position and detailed cellular morphology. Based on these results, we conclude that EAP recordings are an excellent source of data for the purpose of constraining compartmental models.

  13. Sodium action potentials in the dendrites of cerebellar Purkinje cells.

    PubMed

    Regehr, W G; Konnerth, A; Armstrong, C M

    1992-06-15

    We report here that in cerebellar Purkinje cells from which the axon has been removed, positive voltage steps applied to the voltage-clamped soma produce spikes of active current. The spikes are inward, are all-or-none, have a duration of approximately 1 ms, and are reversibly eliminated by tetrodotoxin, a Na channel poison. From cell to cell, the amplitude of the spikes ranges from 4 to 20 nA. Spike latency decreases as the depolarizing step is made larger. These spikes clearly arise at a site where the voltage is not controlled, remote from the soma. From these facts we conclude that Purkinje cell dendrites contain a sufficient density of Na channels to generate action potentials. Activation by either parallel fiber or climbing fiber synapses produces similar spikes, suggesting that normal input elicits Na action potentials in the dendrites. These findings greatly alter current views of how dendrites in these cells respond to synaptic input.

  14. Warm body temperature facilitates energy efficient cortical action potentials.

    PubMed

    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.

  15. A review of action estimation methods for galactic dynamics

    NASA Astrophysics Data System (ADS)

    Sanders, Jason L.; Binney, James

    2016-04-01

    We review the available methods for estimating actions, angles and frequencies of orbits in both axisymmetric and triaxial potentials. The methods are separated into two classes. Unless an orbit has been trapped by a resonance, convergent, or iterative, methods are able to recover the actions to arbitrarily high accuracy given sufficient computing time. Faster non-convergent methods rely on the potential being sufficiently close to a separable potential, and the accuracy of the action estimate cannot be improved through further computation. We critically compare the accuracy of the methods and the required computation time for a range of orbits in an axisymmetric multicomponent Galactic potential. We introduce a new method for estimating actions that builds on the adiabatic approximation of Schönrich & Binney and discuss the accuracy required for the actions, angles and frequencies using suitable distribution functions for the thin and thick discs, the stellar halo and a star stream. We conclude that for studies of the disc and smooth halo component of the Milky Way, the most suitable compromise between speed and accuracy is the Stäckel Fudge, whilst when studying streams the non-convergent methods do not offer sufficient accuracy and the most suitable method is computing the actions from an orbit integration via a generating function. All the software used in this study can be downloaded from https://github.com/jls713/tact.

  16. 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

  17. The Characteristics of Action Potentials in Primo Vessels and the Effects of Acetylcholine Injection to the Action Potentials

    PubMed Central

    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. PMID:23861710

  18. Information Encoding and Reconstruction from the Phase of Action Potentials

    PubMed Central

    Nadasdy, Zoltan

    2009-01-01

    Fundamental questions in neural coding are how neurons encode, transfer, and reconstruct information from the pattern of action potentials (APs) exchanged between different brain structures. We propose a general model of neural coding where neurons encode information by the phase of their APs relative to their subthreshold membrane oscillations. We demonstrate by means of simulations that AP phase retains the spatial and temporal content of the input under the assumption that the membrane potential oscillations are coherent across neurons and between structures and have a constant spatial phase gradient. The model explains many unresolved physiological observations and makes a number of concrete, testable predictions about the relationship between APs, local field potentials, and subthreshold membrane oscillations, and provides an estimate of the spatio-temporal precision of neuronal information processing. PMID:19668700

  19. Intracochlear and extracochlear ECAPs suggest antidromic action potentials.

    PubMed

    Miller, Charles A; Abbas, Paul J; Hay-McCutcheon, Marcia J; Robinson, Barbara K; Nourski, Kirill V; Jeng, Fuh-Cherng

    2004-12-01

    With experimental animals, the electrically evoked compound action potential (ECAP) can be recorded from multiple sites (e.g., round window, intracranial and intracochlear sites). However, human ECAPs are typically recorded from intracochlear electrodes of the implanted array. To bridge this difference, we obtained ECAPs from cats using both intracochlear and nerve-trunk recording sites. We also sought to determine how recording the site influences the acquired evoked potential and how those differences may provide insight into basic excitation properties. In the main experiment, ECAPs were recorded from four acutely deafened cats after implanting a Nucleus-style banded electrode array. Potentials were recorded from an electrode positioned on the nerve trunk and an intracochlear electrode. We manipulated stimulus level, electrode configuration (monopolar vs bipolar) and stimulus polarity, variables that influence the site of excitation. Intracochlear ECAPs were found to be an order of magnitude greater than those obtained with the nerve-trunk electrode. Also, compared with the nerve-trunk potentials, the intracochlear ECAPs more closely resembled those obtained from humans in that latencies were shorter and the waveform morphology was typically biphasic (a negative peak followed by a positive peak). With anodic monophasic stimuli, the ECAP had a unique positive-to-negative morphology which we attributed to antidromic action potentials resulting from a relatively central site of excitation. We also collected intracochlear ECAPs from twenty Nucleus 24 implant users. Compared with the feline ECAPs, the human potentials had smaller amplitudes and longer latencies. It is not clear what underlies these differences, although several factors are considered.

  20. Action currents, internodal potentials, and extracellular records of myelinated mammalian nerve fibers derived from node potentials.

    PubMed Central

    Marks, W B; Loeb, G E

    1976-01-01

    The potential distribution within the internodal axon of mammalian nerve fibers is derived by applying known node potential waveforms to the ends of an equivalent circuit model of the internode. The complete spatial/temporal profile of action potentials synthesized from the internodal profiles is used to compute the node current waveforn, and the extracellular action potential around fibers captured within a tubular electrode. For amphibia, the results agreed with empirical values. For mammals, the amplitude of the node currents plotted against conduction velocity was fitted by a straight line. The extracellular potential waveform depended on the location of the nodes within the tube. For tubes of length from 2 to 8 internodes, extracellular wave amplitude (mammals) was about one-third of the product of peak node current and tube resistance (center to ends). The extracellular potentials developed by longitudinal and radial currents in an anisotropic medium (fiber bundle) are compared. PMID:1276389

  1. 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.

  2. Incorporating gravity into trace dynamics: the induced gravitational action

    NASA Astrophysics Data System (ADS)

    Adler, Stephen L.

    2013-10-01

    We study the incorporation of gravity into the trace dynamics framework for classical matrix-valued fields, from which we have proposed that quantum field theory is the emergent thermodynamics, with state vector reduction arising from fluctuation corrections to this thermodynamics. We show that the metric must be incorporated as a classical, not a matrix-valued, field, with the source for gravity the exactly covariantly conserved trace stress-energy tensor of the matter fields. We then study corrections to the classical gravitational action induced by the dynamics of the matrix-valued matter fields, by examining the average over the trace dynamics canonical ensemble of the matter field action, in the presence of a general background metric. Using constraints from global Weyl scaling and three-space general coordinate transformations, we show that to zeroth order in derivatives of the metric, the induced gravitational action in the preferred rest frame of the trace dynamics canonical ensemble must have the form \\begin{equation} \\fl\\Delta S=\\int d^4x (^{(4)}g)^{1/2}(g_{00})^{-2} A (g_{0i}g_{0j}g^{ij}/g_{00},D^ig_{ij}D^j/g_{00},g_{0i}D^i/g_{00} ) , \\end{equation} with Di defined through the co-factor expansion of (4)g by (4)g/(3)g = g00 + g0iDi, and with A(x, y, z) a general function of its three arguments. This action has ‘chameleon-like’ properties: for the Robertson-Walker cosmological metric, it exactly reduces to a cosmological constant, but for the Schwarzschild metric it diverges as (1 - 2M/r)-2 near the Schwarzschild radius, indicating that it may substantially affect the horizon structure.

  3. 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

  4. 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.

  5. Click- and chirp-evoked human compound action potentials.

    PubMed

    Chertoff, Mark; Lichtenhan, Jeffery; Willis, Marie

    2010-05-01

    In the experiments reported here, the amplitude and the latency of human compound action potentials (CAPs) evoked from a chirp stimulus are compared to those evoked from a traditional click stimulus. The chirp stimulus was created with a frequency sweep to compensate for basilar membrane traveling wave delay using the O-Chirp equations from Fobel and Dau [(2004). J. Acoust. Soc. Am. 116, 2213-2222] derived from otoacoustic emission data. Human cochlear traveling wave delay estimates were obtained from derived compound band action potentials provided by Eggermont [(1979). J. Acoust. Soc. Am. 65, 463-470]. CAPs were recorded from an electrode placed on the tympanic membrane (TM), and the acoustic signals were monitored with a probe tube microphone attached to the TM electrode. Results showed that the amplitude and latency of chirp-evoked N1 of the CAP differed from click-evoked CAPs in several regards. For the chirp-evoked CAP, the N1 amplitude was significantly larger than the click-evoked N1s. The latency-intensity function was significantly shallower for chirp-evoked CAPs as compared to click-evoked CAPs. This suggests that auditory nerve fibers respond with more unison to a chirp stimulus than to a click stimulus.

  6. 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…

  7. Narrow and wide field amacrine cells fire action potentials in response to depolarization and light stimulation.

    PubMed

    Heflin, Stephanie J; Cook, Paul B

    2007-01-01

    Action potentials in amacrine cells are important for lateral propagation of signals across the inner retina, but it is unclear how many subclasses of amacrine cells contain voltage-gated sodium channels or can fire action potentials. This study investigated the ability of amacrine cells with narrow ( <200 microm) and wide (>200 microm) dendritic fields to fire action potentials in response to depolarizing current injections and light stimulation. The pattern of action potentials evoked by current injections revealed two distinct classes of amacrine cells; those that responded with a single action potential (single-spiking cells) and those that responded with repetitive action potentials (repetitive-spiking cells). Repetitive-spiking cells differed from single-spiking cells in several regards: Repetitive-spiking cells were more often wide field cells, while single-spiking cells were more often narrow field cells. Repetitive-spiking cells had larger action potential amplitudes, larger peak voltage-gated NaV currents lower action potential thresholds, and needed less current to induce action potentials. However, there was no difference in the input resistance, holding current or time constant of these two classes of cells. The intrinsic capacity to fire action potentials was mirrored in responses to light stimulation; single-spiking amacrine cells infrequently fired action potentials to light steps, while repetitive-spiking amacrine cells frequently fired numerous action potentials. These results indicate that there are two physiologically distinct classes of amacrine cells based on the intrinsic capacity to fire action potentials.

  8. 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

  9. Potential Flow Analysis of Dynamic Ground Effect

    NASA Technical Reports Server (NTRS)

    Feifel, W. M.

    1999-01-01

    Interpretation of some flight test data suggests the presence of a 'dynamic ground effect'. The lift of an aircraft approaching the ground depends on the rate of descent and is lower than the aircraft steady state lift at a same height above the ground. Such a lift deficiency under dynamic conditions could have a serious impact on the overall aircraft layout. For example, the increased pitch angle needed to compensate for the temporary loss in lift would reduce the tail strike margin or require an increase in landing gear length. Under HSR2 an effort is under way to clarify the dynamic ground effect issue using a multi-pronged approach. A dynamic ground effect test has been run in the NASA Langley 14x22 ft wind tunnel. Northup-Grumman is conducting time accurate CFD (Computational Fluid Dynamics) Euler analyses on the National Aerodynamic Simulator facility. Boeing has been using linear potential flow methodology which are thought to provide much needed insight in, physics of this very complex problem. The present report summarizes the results of these potential flow studies.

  10. Atrial cell action potential parameter fitting using genetic algorithms.

    PubMed

    Syed, Z; Vigmond, E; Nattel, S; Leon, L J

    2005-09-01

    Understanding of the considerable variation in action potential (AP) shape throughout the heart is necessary to explain normal and pathological cardiac function. Existing mathematical models reproduce typical APs, but not all measured APs, as fitting the sets of non-linear equations is a tedious process. The study describes the integration of a pre-existing mathematical model of an atrial cell AP with a genetic algorithm to provide an automated tool to generate APs for arbitrary cells by fitting ionic channel conductances. Using the Nygren model as the base, the technique was first verified by starting with random values and fitting the Nygren model to itself with an error of only 0.03%. The Courtemanche model, which has a different morphology from that of the Nygren model, was successfully fitted. The AP duration restitution curve generated by the fit matched that of the target model very well. Finally, experimentally recorded APs were reproduced. To match AP duration restitution behaviour properly, it was necessary simultaneously to fit over several stimulation frequencies. Also, fitting of the upstroke was better if the stimulating current pulse replicated that found in situ as opposed to a rectangular pulse. In conclusion, the modelled parameters were successfully able to reproduce any given atrial AP. This tool can be useful for determining parameters in new AP models, reproducing specific APs, as well as determining the locus of drug action by examining changes in conductance values.

  11. Temperature dependence of action potential parameters in Aplysia neurons.

    PubMed

    Hyun, Nam Gyu; Hyun, Kwang-Ho; Lee, Kyungmin; Kaang, Bong-Kiun

    2012-01-01

    Although the effects of temperature changes on the activity of neurons have been studied in Aplysia, the reproducibility of the temperature dependence of the action potential (AP) parameters has not been verified. To this end, we performed experiments using Aplysia neurons. Fourteen AP parameters were analyzed using the long-term data series recorded during the experiments. Our analysis showed that nine of the AP parameters decreased as the temperature increased: the AP amplitude (A(AP)), membrane potential at the positive peak (V(pp)), interspike interval, first half (Δt(r1)) and last half (Δt(r2)) of the temperature rising phase, first half (Δt(f1)) and last half (Δt(f2)) of the temperature falling phase, AP (Δt(AP, 1/2)), and differentiated signal (Δt(DS, 1/2)) half-width durations. Five of the AP parameters increased with temperature: the differentiated signal amplitude (A(DS)), absolute value of the membrane potential at negative peak (|V(np)|), absolute value of the maximum slope of the AP during the temperature rising (|-MSR|) and falling (|MSF|) phases, and spiking frequency (Frequency). This work could provide the basis for a better understanding of the elementary processes underlying the temperature-dependent neuronal activity in Aplysia.

  12. The dynamic action mechanism of small cationic antimicrobial peptides.

    PubMed

    Lopez Cascales, J J; Garro, A; Porasso, R D; Enriz, R D

    2014-10-21

    Antimicrobial peptides form part of the immune system as protection against the action of external pathogens. The differences that exist between mammalian and microbial cell membrane architectures are key aspects of the ability of these peptides to discriminate between pathogens and host cells. Given that the pathogen membrane is the non-specific target of these cationic peptides, different molecular mechanisms have been suggested to describe the rules that permit them to distinguish between pathogens and mammalian cells. In this context, and setting aside the old fashion idea that cationic peptides act through one mechanism alone, this work will provide insight into the molecular action mechanism of small antimicrobial peptides, based on molecular dynamics simulations of phospholipid bilayers that mimic different cell membrane architectures. After measuring different properties of these lipid bilayers, in the absence and presence of peptides, a four-step action mechanism was suggested on the basis of the formation of phospholipid rafts induced by the presence of these cationic peptides. Thus, this work shows how differences in the bending modulus (k(b)) of these lipid rafts and differences in the free energy profiles (ΔG(z)) associated with the insertion of these peptides into these lipid rafts are key aspects for explaining the action mechanism of these cationic peptides at the molecular level.

  13. Dynamic Structure of Joint-Action Stimulus-Response Activity

    PubMed Central

    Malone, MaryLauren; Castillo, Ramon D.; Kloos, Heidi; Holden, John G.; Richardson, Michael J.

    2014-01-01

    The mere presence of a co-actor can influence an individual’s response behavior. For instance, a social Simon effect has been observed when two individuals perform a Go/No-Go response to one of two stimuli in the presence of each other, but not when they perform the same task alone. Such effects are argued to provide evidence that individuals co-represent the task goals and the to-be-performed actions of a co-actor. Motivated by the complex-systems approach, the present study was designed to investigate an alternative hypothesis — that such joint-action effects are due to a dynamical (time-evolving) interpersonal coupling that operates to perturb the behavior of socially situated actors. To investigate this possibility, participants performed a standard Go/No-Go Simon task in joint and individual conditions. The dynamic structure of recorded reaction times was examined using fractal statistics and instantaneous cross-correlation. Consistent with our hypothesis that participants responding in a shared space would become behaviorally coupled, the analyses revealed that reaction times in the joint condition displayed decreased fractal structure (indicative of interpersonal perturbation processes modulating ongoing participant behavior) compared to the individual condition, and were more correlated across a range of time-scales compared to the reaction times of pseudo-pair controls. Collectively, the findings imply that dynamic processes might underlie social stimulus-response compatibility effects and shape joint cognitive processes in general. PMID:24558467

  14. Restitution slope is principally determined by steady-state action potential duration.

    PubMed

    Shattock, Michael J; Park, Kyung Chan; Yang, Hsiang-Yu; Lee, Angela Wc; Niederer, Steve; MacLeod, Kenneth T; Winter, James

    2017-03-23

    AimsThe steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF.Methods and ResultsExperiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalising the restitution curve as a % of steady-state APD abolished the difference in restitution curves by all interventions. Altered restitution dynamics were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM, to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope.Conclusion(s)Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce

  15. 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

  16. Kink's dynamics for a deformable substrate potential

    NASA Astrophysics Data System (ADS)

    Tchofo Dinda, P.; Willis, C. R.

    1994-01-01

    We study the static and dynamic properties of a kink in a chain of harmonically coupled atoms subjected to a deformable double-well substrate potential. We treat intrinsically the lattice discreteness without approximation and show that in some deformation-parameter ranges each period of the PN (Peierls-Nabarro) potential consists of two wells whose minima are located respectively on a lattice site and midway between two adjacent sites of the chain. In some other parameter ranges each period of the PN potential posseses a single well whose minimum is located either on a lattice site or midway between two adjacent lattice sites. We examine the kink's dynamics by using a multiple-collective-variable treatment, that is, we derive the exact equations of motion for the collective variables X and Y - which describe respectively the center-of-mass mode and the internal mode of the kink. We numerically solve the collective variable equations of motion for the trapped and untrapped regimes of the discrete-kink motion, and show that the presence of a nonlinear internal mode makes a contribution of particular importance in the discrete-kink's dynamics. Indeed, we show that during its untrapped regime, the discrete kink can undergo one or more temporary trappings and even a reflection back over several PN wells, and relate such behaviours to the effects of the excitations of the internal mode of the kink.

  17. Dynamic similarity promotes interpersonal coordination in joint action.

    PubMed

    Słowiński, Piotr; Zhai, Chao; Alderisio, Francesco; Salesse, Robin; Gueugnon, Mathieu; Marin, Ludovic; Bardy, Benoit G; di Bernardo, Mario; Tsaneva-Atanasova, Krasimira

    2016-03-01

    Human movement has been studied for decades, and dynamic laws of motion that are common to all humans have been derived. Yet, every individual moves differently from everyone else (faster/slower, harder/smoother, etc.). We propose here an index of such variability, namely an individual motor signature (IMS) able to capture the subtle differences in the way each of us moves. We show that the IMS of a person is time-invariant and that it significantly differs from those of other individuals. This allows us to quantify the dynamic similarity, a measure of rapport between dynamics of different individuals' movements, and demonstrate that it facilitates coordination during interaction. We use our measure to confirm a key prediction of the theory of similarity that coordination between two individuals performing a joint-action task is higher if their motions share similar dynamic features. Furthermore, we use a virtual avatar driven by an interactive cognitive architecture based on feedback control theory to explore the effects of different kinematic features of the avatar motion on coordination with human players.

  18. Dynamic similarity promotes interpersonal coordination in joint action

    PubMed Central

    Słowiński, Piotr; Zhai, Chao; Alderisio, Francesco; Salesse, Robin; Gueugnon, Mathieu; Marin, Ludovic; Bardy, Benoit G.; di Bernardo, Mario; Tsaneva-Atanasova, Krasimira

    2016-01-01

    Human movement has been studied for decades, and dynamic laws of motion that are common to all humans have been derived. Yet, every individual moves differently from everyone else (faster/slower, harder/smoother, etc.). We propose here an index of such variability, namely an individual motor signature (IMS) able to capture the subtle differences in the way each of us moves. We show that the IMS of a person is time-invariant and that it significantly differs from those of other individuals. This allows us to quantify the dynamic similarity, a measure of rapport between dynamics of different individuals' movements, and demonstrate that it facilitates coordination during interaction. We use our measure to confirm a key prediction of the theory of similarity that coordination between two individuals performing a joint-action task is higher if their motions share similar dynamic features. Furthermore, we use a virtual avatar driven by an interactive cognitive architecture based on feedback control theory to explore the effects of different kinematic features of the avatar motion on coordination with human players. PMID:27009178

  19. Constraining the Galactic potential via action-based distribution functions for mono-abundance stellar populations

    NASA Astrophysics Data System (ADS)

    Ting, Yuan-Sen; Rix, Hans-Walter; Bovy, Jo; van de Ven, Glenn

    2013-09-01

    We present a rigorous and practical way of constraining the Galactic potential based on the phase-space information for many individual stars. Such an approach is needed to dynamically model the data from ongoing spectroscopic surveys of the Galaxy and in the future Gaia. This approach describes the orbit distribution of stars by a family of parametrized distribution function (DF) proposed by McMillan and Binney, which are based on actions. We find that these parametrized DFs are flexible enough to capture well the observed phase-space distributions of individual abundance-selected Galactic subpopulations of stars (`mono-abundance populations') for a disc-like gravitational potential, which enables independent dynamical constraints from each of the Galactic mono-abundance populations. We lay out a statistically rigorous way to constrain the Galactic potential parameters by constructing the joint likelihood of potential and DF parameters, and subsequently marginalizing over the DF parameters. This approach explicitly incorporates the spatial selection function inherent to all Galactic surveys, and can account for the uncertainties of the individual position-velocity observations. On that basis, we study the precision of the parameters of the Galactic potential that can be reached with various sample sizes and realistic spatial selection functions. By creating mock samples from the DF, we show that, even under a restrictive and realistic spatial selection function, given a two-parameter gravitational potential, one can recover the true potential parameters to a few per cent with sample sizes of a few thousands. The assumptions of axisymmetry, of DFs that are smooth in the actions and of no time variation remain important limitations in our current study.

  20. Metabolic Energy of Action Potentials Modulated by Spike Frequency Adaptation

    PubMed Central

    Yi, Guo-Sheng; Wang, Jiang; Li, Hui-Yan; Wei, Xi-Le; Deng, Bin

    2016-01-01

    Spike frequency adaptation (SFA) exists in many types of neurons, which has been demonstrated to improve their abilities to process incoming information by synapses. The major carrier used by a neuron to convey synaptic signals is the sequences of action potentials (APs), which have to consume substantial metabolic energies to initiate and propagate. Here we use conductance-based models to investigate how SFA modulates the AP-related energy of neurons. The SFA is attributed to either calcium-activated K+ (IAHP) or voltage-activated K+ (IM) current. We observe that the activation of IAHP or IM increases the Na+ load used for depolarizing membrane, while produces few effects on the falling phase of AP. Then, the metabolic energy involved in Na+ current significantly increases from one AP to the next, while for K+ current it is less affected. As a consequence, the total energy cost by each AP gets larger as firing rate decays down. It is also shown that the minimum Na+ charge needed for the depolarization of each AP is unaffected during the course of SFA. This indicates that the activation of either adaptation current makes APs become less efficient to use Na+ influx for their depolarization. Further, our simulations demonstrate that the different biophysical properties of IM and IAHP result in distinct modulations of metabolic energy usage for APs. These investigations provide a fundamental link between adaptation currents and neuronal energetics, which could facilitate to interpret how SFA participates in neuronal information processing. PMID:27909394

  1. Steroid inhibitors of androgen-potentiated actions on skin.

    PubMed

    Ebling, F J; Randall, V A

    1983-07-01

    Antiandrogens, such as cyproterone acetate, and oestrogens both inhibit sebaceous secretion in rats and have a potentiality for the treatment of hirsutism and acne in the human female. However, they act at different points. In castrated rats treated with testosterone, 3 micrograms/day oestradiol produced a greater decrease in sebum secretion than a dose of cyproterone acetate over 1000 times larger; moreover the antiandrogen reduced the incidence of sebaceous mitoses whereas the oestradiol did not. In hirsute women, oral administration of 100 mg of cyproterone acetate daily caused a 40% reduction in sebum secretion within 10 days; a further 20% was subsequently produced by combined therapy with cyproterone acetate and ethinyloestradiol. Significant decreases in the diameter and rate of growth of thigh hairs were not established until around the fourth monthly cycle of treatment. The actions were believed to be mainly peripheral, though contributory factors could also have been the small but significant reductions in plasma androgens produced by the antiandrogen, and the marked rise in sex hormone binding globulin produced by the oestrogen. That it is theoretically possible for cyproterone acetate or oestradiol to act locally follows from an unequivocal demonstration that either compound produced a local depression of sebum secretion when applied topically to rats.

  2. Ultrafast action potentials mediate kilohertz signaling at a central synapse.

    PubMed

    Ritzau-Jost, Andreas; Delvendahl, Igor; Rings, Annika; Byczkowicz, Niklas; Harada, Harumi; Shigemoto, Ryuichi; Hirrlinger, Johannes; Eilers, Jens; Hallermann, Stefan

    2014-10-01

    Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported in vivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission up to ∼1 kHz. Presynaptic APs are ultrafast, with ∼100 μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca(2+) channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling.

  3. 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.

  4. SHAPING OF ACTION POTENTIALS BY TYPE I AND TYPE II BK CHANNELS

    PubMed Central

    Jaffe, David B.; Wang, Bin; Brenner, Robert

    2011-01-01

    The BK channel is a Ca2+ and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca2+ was high (>20 µM) and the other where BK-activating Ca2+ was low (~0.4–1.2 µM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca2+ channels due to electrogenic effects on spike duration. We also found that depending on Ca2+ dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron. PMID:21723921

  5. Dynamic Aspects of Cochlear Microphonic Potentials

    NASA Astrophysics Data System (ADS)

    Meenderink, Sebastiaan W. F.; van der Heijden, Marcel

    2011-11-01

    Cochlear microphonic potentials were recorded from the Mongolian gerbil in response to low-frequency auditory stimuli. Provided that contamination of the potentials by the phase-locked neurophonic is avoided, these recordings can be interpreted "as if recorded from a single outer hair cell". It is found that the instantaneous I/O-curves resemble the well-known Boltzmann activation curve. The dynamic aspect of the I/O-curves does reveal hysteresis and a level-dependent gain that is not observed in static measures of these curves. We explore a model that simulates CM generation from hair cell populations, but find it inadequate to reproduce the data. Rather, there seem to be fast, adaptive mechanisms probably at the level of the transduction channels themselves.

  6. Development of action potentials and apamin-sensitive after-potentials in mouse vestibular nucleus neurones.

    PubMed

    Dutia, M B; Johnston, A R

    1998-01-01

    The postnatal maturation of medial vestibular nucleus (MVN) neurones was examined in slices of the dorsal brainstem prepared from balb/c mice at specific stages during the first postnatal month. Using spike-shape averaging to analyse the intracellularly recorded action potentials and after-hyperpolarizations (AHPs) in each cell, all the MVN neurones recorded in the young adult (postnatal day 30; P30) mouse were shown to have either a single deep AHP (type A cells), or an early fast and a delayed slow AHP (type B cells). The relative proportions of the two subtypes were similar to those in the young adult rat. At P5, all the MVN cells recorded showed immature forms of either the type A or the type B action potential shape. Immature type A cells had broad spontaneous spikes, and the characteristic single AHP was small in amplitude. Immature type B cells had somewhat narrower spontaneous spikes that were followed by a delayed, apamin-sensitive AHP. The delayed AHP was separated from the repolarisation phase of the spike by a period of isopotentiality. Over the period P10-P15, the mean resting potentials of the MVN cells became more negative, their action potential fall-times became shorter, the single AHP in type A cells became deeper, and the early fast AHP appeared in type B cells. Until P15 cells of varying degrees of electrophysiological maturity were found in the MVN but by P30 all MVN cells recorded were typical adult type A or type B cells. Exposure to the selective blocker of SK-type Ca-activated K channels, apamin (0.3 microM), induced depolarising plateaux and burst firing in immature type B cells at rest. The duration of the apamin-induced bursts and the spike frequency during the bursts were reduced but not abolished after blockade of Ca channels in Ca-free artificial cerebrospinal fluid containing Cd2+. By contrast, in mature type B cells at rest apamin selectively abolished the delayed slow AHP but did not induce bursting activity. Apamin had no effect

  7. Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

    PubMed

    Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

    2008-02-01

    Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

  8. Dynamic remedial action scheme using online transient stability analysis

    NASA Astrophysics Data System (ADS)

    Shrestha, Arun

    Economic pressure and environmental factors have forced the modern power systems to operate closer to their stability limits. However, maintaining transient stability is a fundamental requirement for the operation of interconnected power systems. In North America, power systems are planned and operated to withstand the loss of any single or multiple elements without violating North American Electric Reliability Corporation (NERC) system performance criteria. For a contingency resulting in the loss of multiple elements (Category C), emergency transient stability controls may be necessary to stabilize the power system. Emergency control is designed to sense abnormal conditions and subsequently take pre-determined remedial actions to prevent instability. Commonly known as either Remedial Action Schemes (RAS) or as Special/System Protection Schemes (SPS), these emergency control approaches have been extensively adopted by utilities. RAS are designed to address specific problems, e.g. to increase power transfer, to provide reactive support, to address generator instability, to limit thermal overloads, etc. Possible remedial actions include generator tripping, load shedding, capacitor and reactor switching, static VAR control, etc. Among various RAS types, generation shedding is the most effective and widely used emergency control means for maintaining system stability. In this dissertation, an optimal power flow (OPF)-based generation-shedding RAS is proposed. This scheme uses online transient stability calculation and generator cost function to determine appropriate remedial actions. For transient stability calculation, SIngle Machine Equivalent (SIME) technique is used, which reduces the multimachine power system model to a One-Machine Infinite Bus (OMIB) equivalent and identifies critical machines. Unlike conventional RAS, which are designed using offline simulations, online stability calculations make the proposed RAS dynamic and adapting to any power system

  9. Disappearing inflaton potential via heavy field dynamics

    SciTech Connect

    Kitajima, Naoya; Takahashi, Fuminobu E-mail: fumi@tuhep.phys.tohoku.ac.jp

    2016-02-01

    We propose a possibility that the inflaton potential is significantly modified after inflation due to heavy field dynamics. During inflation such a heavy scalar field may be stabilized at a value deviated from the low-energy minimum. In extreme cases, the inflaton potential vanishes and the inflaton becomes almost massless at some time after inflation. Such transition of the inflaton potential has interesting implications for primordial density perturbations, reheating, creation of unwanted relics, dark radiation, and experimental search for light degrees of freedom. To be concrete, we consider a chaotic inflation in supergravity where the inflaton mass parameter is promoted to a modulus field, finding that the inflaton becomes stable after the transition and contributes to dark matter. Another example is a hilltop inflation (also called new inflation) by the MSSM Higgs field which acquires a large expectation value just after inflation, but it returns to the origin after the transition and finally rolls down to the electroweak vacuum. Interestingly, the smallness of the electroweak scale compared to the Planck scale is directly related to the flatness of the inflaton potential.

  10. Dynamic in vivo quadriceps lines-of-action.

    PubMed

    Wilson, Nicole A; Sheehan, Frances T

    2010-08-10

    Tissue stresses and quadriceps forces are crucial factors when considering knee joint biomechanics. However, it is difficult to obtain direct, in vivo, measurements of these quantities. The primary purpose of this study was to provide the first complete description of quadriceps geometry (force directions and moment arms) of individual quadriceps components using in vivo, 3D data collected during volitional knee extension. A secondary purpose was to determine if 3D quadriceps geometry is altered in patients with patellofemoral pain and maltracking. After obtaining informed consent, cine-phase contrast (PC) MRI sets (x,y,z velocity and anatomic images) were acquired from 25 asymptomatic knees and 15 knees with patellofemoral pain during active knee extension. Using a sagittal-oblique and two coronal-oblique imaging planes, the origins and insertions of each quadriceps line-of-action were identified and tracked throughout the motion by integrating the cine-PC velocity data. The force direction and relative moment (RM) were calculated for each line-of-action. All quadriceps lines-of-action were oriented primarily in the superior direction. There were no significant differences in quadriceps geometry between asymptomatic and subjects with patellofemoral pain. However, patellofemoral kinematics were significantly different between the two populations. This study will improve the ability of musculoskeletal models to closely match in vivo human performance by providing accurate 3D quadriceps geometry and associated patellofemoral kinematics during dynamic knee motion. Furthermore, determination that quadriceps geometry is not altered in patellofemoral pain supports the use of generalized a knee model based on asymptomatic quadriceps architecture.

  11. Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons.

    PubMed

    Hlubek, M D; Cobbett, P

    2000-09-15

    Recordings were made from magnocellular neuroendocrine cells dissociated from the supraoptic nucleus of the adult guinea pig to determine the role of voltage gated K(+) channels in controlling the duration of action potentials and in mediating frequency-dependent action potential broadening exhibited by these neurons. The K(+) channel blockers charybdotoxin (ChTx), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) increased the duration of individual action potentials indicating that multiple types of K(+) channel are important in controlling action potential duration. The effect of these K(+) channel blockers was almost completely reversed by simultaneous blockade of voltage gated Ca(2+) channels with Cd(2+). Frequency-dependent action potential broadening was exhibited by these neurons during trains of action potentials elicited by membrane depolarizing current pulses presented at 10 Hz but not at 1 Hz. 4-AP but not ChTx or TEA inhibited frequency-dependent action potential broadening indicating that frequency-dependent action potential broadening is dependent on increasing steady-state inactivation of A-type K(+) channels (which are blocked by 4-AP). A model of differential contributions of voltage gated K(+) channels and voltage gated Ca(2+) channels to frequency-dependent action potential broadening, in which an increase of Ca(2+) current during each successive action potential is permitted as a result of the increasing steady-state inactivation of A-type K(+) channels, is presented.

  12. 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.

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

    PubMed Central

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

    2016-01-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could impact broadly fundamental scientific and clinical studies, yet realization lacks effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and sub-millisecond time-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 multi-site stimulation and mapping to manipulate actively 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. PMID:27347837

  14. 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.

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

    PubMed

    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.

  16. Ontogeny of Vestibular Compound Action Potentials in the Domestic Chicken

    PubMed Central

    M. Jones, Sherri

    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 μV/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. PMID:11545229

  17. 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.

  18. 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,…

  19. Action-Based Dynamical Modeling for the Milky Way Disk

    NASA Astrophysics Data System (ADS)

    Trick, Wilma H.; Bovy, Jo; Rix, Hans-Walter

    2016-10-01

    We present RoadMapping, a full-likelihood dynamical modeling machinery that aims to recover the Milky Way’s (MW) gravitational potential from large samples of stars in the Galactic disk. RoadMapping models the observed positions and velocities of stars with a parameterized, three-integral distribution function (DF) in a parameterized axisymmetric potential. We investigate through differential test cases with idealized mock data how the breakdown of model assumptions and data properties affect constraints on the potential and DF. Our key results are: (i) If the MW’s true potential is not included in the assumed model potential family, we can—in the axisymmetric case—still find a robust estimate for the potential, with only ≲ 10 % difference in surface density within | z| ≤slant 1.1 {kpc} inside the observed volume. (ii) Modest systematic differences between the true and model DF are inconsequential. E.g., when binning stars to define sub-populations with simple DFs, binning errors do not affect the modeling as long as the DF parameters of neighboring bins differ by \\lt 20 % . In addition, RoadMapping ensures unbiased potential estimates for either (iii) small misjudgements of the spatial selection function (i.e., ≲ 15 % at the survey volume’s edge), (iv) if distances are known to within 10%, or (v) if proper motion uncertainties are known within 10% or are smaller than δ μ ≲ 1 {mas} {{yr}}-1. Challenges are the rapidly increasing computational costs for large sample sizes. Overall, RoadMapping is well suited to making precise new measurements of the MW’s potential with data from the upcoming Gaia releases.

  20. 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.

  1. Hydrogen peroxide decelerates recovery of action potential after high-frequency fatigue in skeletal muscle.

    PubMed

    Oba, T; Ishikawa, T; Takaishi, T; Aoki, T; Yamaguchi, M

    2000-10-01

    Effects of reactive oxygen species (ROS), especially hydrogen peroxide (H(2)O(2)), on recovery of action potential by resting for 30 min after high-frequency fatigue were studied using frog skeletal muscle fibers. After stimulation at a frequency of 50 HZ for 2 min, the action potential amplitude was decreased by 14.5 mV from controls, and resting membrane was depolarized by 15.4 mV. Action potential duration was also prolonged by high-frequency stimulation (1.5 ms in controls to 2.6 ms). The high-frequency stimulation used here caused no muscle damage. The action potential was partially improved after a 30-min rest. Addition of catalase at 500 units/ml or H(2)O(2) at 0.5 mM to sartorius muscle did not alter any of the parameters of the action potential after high-frequency stimulation. Treatment with catalase accelerated post-fatigue recovery of the action potential. Application of H(2)O(2) delayed post-fatigue recovery of resting and action potentials. When added to detubulated toe muscle fibers, catalase no longer improved the attenuation of action potential induced by high-frequency stimulation, even after a 30-min rest. These findings suggest that removal of H(2)O(2) from transverse tubules is effective for post-fatigue recovery of action potential in skeletal muscle.

  2. On the excitation of action potentials by protons and its potential implications for cholinergic transmission.

    PubMed

    Fillafer, Christian; Schneider, Matthias F

    2016-03-01

    One of the most conserved mechanisms for transmission of a nerve pulse across a synapse relies on acetylcholine (ACh). Ever since the Nobel Prize-winning works of Dale and Loewi, it has been assumed that ACh-subsequent to its action on a postsynaptic cell-is split into inactive by-products by acetylcholinesterase (AChE). Herein, the widespread assumption of inactivity of ACh's hydrolysis products is falsified. Excitable cells (Chara braunii internodes), which had previously been unresponsive to ACh, became ACh-sensitive in the presence of AChE. The latter was evidenced by a striking difference in cell membrane depolarization upon exposure to 10 mM intact ACh (∆V = -2 ± 5 mV) and its hydrolysate (∆V = 81 ± 19 mV), respectively, for 60 s. This pronounced depolarization, which also triggered action potentials, was clearly attributed to one of the hydrolysis products: acetic acid (∆V = 87 ± 9 mV at pH 4.0; choline ineffective in the range 1-10 mM). In agreement with our findings, numerous studies in the literature have reported that acids excite gels, lipid membranes, plant cells, erythrocytes, as well as neurons. Whether excitation of the postsynaptic cell in a cholinergic synapse is due to protons or due to intact ACh is a most fundamental question that has not been addressed so far.

  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. 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.

  5. 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

  6. [Phenibut potentiation of the therapeutic action of antiparkinson agents].

    PubMed

    Gol'dblat, Iu V; Lapin, I P

    1986-01-01

    It was observed in experiments on mice that the central action of phenibut (beta-phenyl-gamma-aminobutyric acid) diminished after destruction of brain dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the dopamine receptor blocker haloperidol which suggests the dopaminergic component in the action of phenibut. In 13 of 16 patients receiving long-term treatment with antiparkinsonic drugs, addition of phenibut (0.25 g thrice daily for 10 days) resulted in marked clinical improvement with a significant increase of motor activity, as well as diminution of both rigidity and tremor. Follow-up showed a significant lowering of muscle tone of rigid muscles, augmentation of their strength and amplitude of movements. In 8 patients receiving phenibut without antiparkinsonic drugs the results were negligible.

  7. Supernormal Conduction and Suppression of Spatially Discordant Alternans of Cardiac Action Potentials

    PubMed Central

    Jing, Linyuan; Agarwal, Anuj; Patwardhan, Abhijit

    2016-01-01

    Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate this subtlety, we simulated this phenomenon using two approaches; (1) by using the standard, i.e., S1S2 protocol to quantify restitution and disabling the slow inactivation gate j of the sodium current (INa), and (2) by using the dynamic, i.e., S1S1 protocol for quantification of restitution and increasing INa at different cycle lengths (CL). Even though both approaches produced similar CV restitution curves, DA was suppressed only during the first approach, where the CV of the short of the long-short action potential (AP) pattern was selectively increased. These results show that negative CV restitution, which is considered characteristic of SNC, per se, is not causal in suppressing DA, rather, the critical factor is a change in the ratio of the velocities of the short and the long APs. PMID:26779035

  8. 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.…

  9. Modeling the Mass Action Dynamics of Metabolism with Fluctuation Theorems and Maximum Entropy

    NASA Astrophysics Data System (ADS)

    Cannon, William; Thomas, Dennis; Baxter, Douglas; Zucker, Jeremy; Goh, Garrett

    The laws of thermodynamics dictate the behavior of biotic and abiotic systems. Simulation methods based on statistical thermodynamics can provide a fundamental understanding of how biological systems function and are coupled to their environment. While mass action kinetic simulations are based on solving ordinary differential equations using rate parameters, analogous thermodynamic simulations of mass action dynamics are based on modeling states using chemical potentials. The latter have the advantage that standard free energies of formation/reaction and metabolite levels are much easier to determine than rate parameters, allowing one to model across a large range of scales. Bridging theory and experiment, statistical thermodynamics simulations allow us to both predict activities of metabolites and enzymes and use experimental measurements of metabolites and proteins as input data. Even if metabolite levels are not available experimentally, it is shown that a maximum entropy assumption is quite reasonable and in many cases results in both the most energetically efficient process and the highest material flux.

  10. Antimalarial action of hydroxamate-based iron chelators and potentiation of desferrioxamine action by reversed siderophores.

    PubMed Central

    Golenser, J; Tsafack, A; Amichai, Y; Libman, J; Shanzer, A; Cabantchik, Z I

    1995-01-01

    Hydroxamate-based chelators of iron are potent inhibitors of in vitro growth of Plasmodium falciparum. Two types of such chelators, the natural desferrioxamine and the synthetic reversed siderophore RSFileum2, are prototypes of antimalarial agents whose action spectra differ in the speed of action, stage dependence, and degree of reversibility of effects. This work explores the possibility of improving the antimalarial efficacy of these agents by using them in various combinations on in vitro cultures of P. falciparum. Growth assessment was based both on total nucleic acid synthesis and on parasitemia. The results indicate that the synthetic reversed siderophore more than complements the antimalarial action of desferrioxamine when applied during either ring, trophozoite, or mixed stages. The combined drug effects were significantly higher than the additive effect of the individual drugs. Qualitatively similar results were obtained for both reversible effects and irreversible (i.e., sustained) effects. Following an 8-h window of exposure the combined drug treatment caused parasite growth arrest and prevented its recovery, even 3 days after the treatment. The fact that such a combination of iron chelators displays a wider action spectrum than either drug alone has implications for the design of chemotherapy regimens. PMID:7695330

  11. Action potentials and twitch forces of rabbit masseter motor units at optimum jaw angle.

    PubMed

    van Eijden, T M G J; Turkawski, S J J

    2002-08-01

    This study examines mutual correlations between electrical and contractile motor-unit properties. Action potentials and twitch force responses of 42 masseter motor units were recorded in 14 rabbits. Motor units were excited by stimulating motoneurones in the trigeminal motor nucleus. Action potentials and twitches were measured at different jaw gapes between 0 and 21 degrees, in steps of 3 degrees. For each motor unit, the jaw angle-active force interrelation was determined and variables for action potential and force were compared at the jaw angle at which the motor unit produced the largest force. The results showed a large variation in variables for action potential and force, possibly related to the variation in motor-unit morphology. A weak correlation was found between the variables for action-potential amplitude and the magnitude of optimum force, indicating that motor units producing larger forces tended to have action potentials with larger amplitudes. Twitch-contraction time and the moment arm of the motor unit correlated positively with both the median frequency and the duration of the action potential. This indicates that slower contracting motor units had longer action potentials and is in accord with the earlier observation that slower motor units are preferentially located in the anterior regions of the masseter.

  12. Vehicle bridge interaction dynamics and potential applications

    NASA Astrophysics Data System (ADS)

    Yang, Y. B.; Lin, C. W.

    2005-06-01

    The dynamic interaction between a moving vehicle and the sustaining bridge is studied. By the method of modal superposition, closed-form solutions are obtained for the vertical responses of both the bridge and moving vehicle, assuming the vehicle/bridge mass ratio to be small. For both the bridge and vehicle responses, it is confirmed that rather accurate solutions can be obtained by considering only the first mode. The displacement, velocity, and acceleration of the bridge are governed at different extents by two sets of frequencies, i.e., the driving frequency of the vehicle and natural frequencies of the bridge. From the spectrum for the bridge displacement, the vehicle speeds can be shown to be associated with some low-frequency pikes. On the other hand, the vehicle responses are governed by five distinct frequencies that appear as driving frequencies, vehicle frequency, and bridge frequencies with shift. From the vehicle's acceleration spectrum, the first bridge frequency (with shift) is shown to have rather high visibility and can be easily identified. The effects of damping of the vehicle and bridge are evaluated in the numerical studies. Potential applications of the present results, as well as further researches required, are also indicated in the paper.

  13. Action potential evoked transmitter release in central synapses: insights from the developing calyx of Held

    PubMed Central

    2009-01-01

    Chemical synapses are the fundamental units that mediate communication between neurons in the mammalian brain. In contrast to the enormous progress made in mapping out postsynaptic contributions of receptors, scaffolding structures and receptor trafficking to synaptic transmission and plasticity, the small size of nerve terminals has largely precluded direct analyses of presynaptic modulation of excitability and transmitter release in central synapses. Recent studies performed in accessible synapses such as the calyx of Held, a giant axosomatic synapse in the sound localization circuit of the auditory brainstem, have provided tremendous insights into how central synapses regulate the dynamic gain range of synaptic transmission. This review will highlight experimental evidence that resolves several long-standing issues with respect to intricate interplays between the waveform of action potentials, Ca2+ currents and transmitter release and further conceptualize their relationships in a physiological context with theoretical models of the spatial organization of voltage-gated Ca2+ channels and synaptic vesicles at release sites. PMID:19939269

  14. Experimental and theoretical description of higher order periods in cardiac tissue action potential duration

    NASA Astrophysics Data System (ADS)

    Herndon, Conner; Fenton, Flavio; Uzelac, Ilija

    Much theoretical, experimental, and clinical research has been devoted to investigating the initiation of cardiac arrhythmias by alternans, the first period doubling bifurcation in the duration of cardiac action potentials. Although period doubling above alternans has been shown to exist in many mammalian hearts, little is understood about their emergence or behavior. There currently exists no physiologically correct theory or model that adequately describes and predicts their emergence in stimulated tissue. In this talk we present experimental data of period 2, 4, and 8 dynamics and a mathematical model that describes these bifurcations. This model extends current cell models through the addition of memory and includes spatiotemporal nonlinearities arising from cellular coupling by tissue heterogeneity.

  15. Distributed computing for membrane-based modeling of action potential propagation.

    PubMed

    Porras, D; Rogers, J M; Smith, W M; Pollard, A E

    2000-08-01

    Action potential propagation simulations with physiologic membrane currents and macroscopic tissue dimensions are computationally expensive. We, therefore, analyzed distributed computing schemes to reduce execution time in workstation clusters by parallelizing solutions with message passing. Four schemes were considered in two-dimensional monodomain simulations with the Beeler-Reuter membrane equations. Parallel speedups measured with each scheme were compared to theoretical speedups, recognizing the relationship between speedup and code portions that executed serially. A data decomposition scheme based on total ionic current provided the best performance. Analysis of communication latencies in that scheme led to a load-balancing algorithm in which measured speedups at 89 +/- 2% and 75 +/- 8% of theoretical speedups were achieved in homogeneous and heterogeneous clusters of workstations. Speedups in this scheme with the Luo-Rudy dynamic membrane equations exceeded 3.0 with eight distributed workstations. Cluster speedups were comparable to those measured during parallel execution on a shared memory machine.

  16. Dynamics of Social Interaction: Kinematic Analysis of a Joint Action.

    PubMed

    Moreau, Quentin; Galvan, Lucie; Nazir, Tatjana A; Paulignan, Yves

    2016-01-01

    Non-verbal social interaction between humans requires accurate understanding of the others' actions. The cognitivist approach suggests that successful interaction depends on the creation of a shared representation of the task, where the pairing of perceptive and motor systems of partners allows inclusion of the other's goal into the overarching representation. Activity of the Mirror Neurons System (MNS) is thought to be a crucial mechanism linking two individuals during a joint action through action observation. The construction of a shared representation of an interaction (i.e., joint action) depends upon sensorimotor cognitive processes that modulate the ability to adapt in time and space. We attempted to detect individuals' behavioral/kinematic change resulting in a global amelioration of performance for both subjects when a common representation of the action is built using a repetitive joint action. We asked pairs of subjects to carry out a simple task where one puts a base in the middle of a table and the other places a parallelepiped fitting into the base, the crucial manipulation being that participants switched roles during the experiment. We aimed to show that a full comprehension of a joint action is not an automatic process. We found that, before switching the interactional role, the participant initially placing the base orientated it in a way that led to an uncomfortable action for participants placing the parallelepiped. However, after switching roles, the action's kinematics by the participant who places the base changed in order to facilitate the action of the other. More precisely, our data shows significant modulation of the base angle in order to ease the completion of the joint action, highlighting the fact that a shared knowledge of the complete action facilitates the generation of a common representation. This evidence suggests the ability to establish an efficient shared representation of a joint action benefits from physically taking our

  17. Prolonged modification of action potential shape by synaptic inputs in molluscan neurones.

    PubMed

    Winlow, W

    1985-01-01

    1. Somatic action potentials of Lymnaea neurons are modified by excitatory or inhibitory synaptic inputs and have been studied using phase-plane techniques and an action potential duration monitor. 2. Excitatory synaptic inputs increase the rate of neuronal discharge, cause action potential broadening, a decrease in the maximum rate of depolarization (Vd) and a decrease in the maximum rate of repolarization (Vr). 3. Inhibitory synaptic inputs decrease the discharge rate and cause narrowing of action potentials, an increase in Vd and an increase in Vr. 4. The effects reported above outlast the original synaptic inputs by many seconds and, if the somatic action potentials are similar to those in the axon terminals, they may have far-reaching effects on transmitter release.

  18. Action potentials of isolated single muscle fibers recorded by potential-sensitive dyes

    PubMed Central

    Nakajima, S.; Gilai, A.

    1980-01-01

    Light transmission changes upon massive stimulation of single muscle fibers of Xenopus were studied with the potential-sensitive nonpermeant dyes, merocyanine rhodanine (WW375) and merocyanine oxazolone (NK2367). Upon stimulation an absorption change (wave a) occurred, which probably represents the sum of action potentials in the transverse tubules and surface membrane. In WW375-stained fibers wave a is a decrease in transmission over the range of 630 to 730 nm (with NK2367, over the range of 590 to 700 nm) but becomes an increase outside this range, thus showing a triphasic spectral pattern. This spectrum differs from that of the squid axon, in which depolarization produces only an increase in transmission over the whole range of wavelengths (Ross et al. 1977. J. Membr. Biol. 33:141-183). When wave a was measured at the edge of the fiber to obtain more signal from the surface membrane, the spectrum did not seem to differ markedly from that obtained from the entire width of the fiber. Thus, the difference in the spectrum between the squid axon and the vertebrate muscle cannot be attributed to the presence of the tubular system. PMID:10822501

  19. Dynamics of Social Interaction: Kinematic Analysis of a Joint Action

    PubMed Central

    Moreau, Quentin; Galvan, Lucie; Nazir, Tatjana A.; Paulignan, Yves

    2016-01-01

    Non-verbal social interaction between humans requires accurate understanding of the others’ actions. The cognitivist approach suggests that successful interaction depends on the creation of a shared representation of the task, where the pairing of perceptive and motor systems of partners allows inclusion of the other’s goal into the overarching representation. Activity of the Mirror Neurons System (MNS) is thought to be a crucial mechanism linking two individuals during a joint action through action observation. The construction of a shared representation of an interaction (i.e., joint action) depends upon sensorimotor cognitive processes that modulate the ability to adapt in time and space. We attempted to detect individuals’ behavioral/kinematic change resulting in a global amelioration of performance for both subjects when a common representation of the action is built using a repetitive joint action. We asked pairs of subjects to carry out a simple task where one puts a base in the middle of a table and the other places a parallelepiped fitting into the base, the crucial manipulation being that participants switched roles during the experiment. We aimed to show that a full comprehension of a joint action is not an automatic process. We found that, before switching the interactional role, the participant initially placing the base orientated it in a way that led to an uncomfortable action for participants placing the parallelepiped. However, after switching roles, the action’s kinematics by the participant who places the base changed in order to facilitate the action of the other. More precisely, our data shows significant modulation of the base angle in order to ease the completion of the joint action, highlighting the fact that a shared knowledge of the complete action facilitates the generation of a common representation. This evidence suggests the ability to establish an efficient shared representation of a joint action benefits from physically

  20. Specific dynamic action in the sunflower star, Pycnopodia helianthoides.

    PubMed

    McGaw, Iain J; Twitchit, Tabitha A

    2012-03-01

    The effects of meal size and meal type on specific dynamic action (SDA) were investigated in a large, active asteroid, the sunflower star, Pycnopodia helianthoides. When the sunflower stars were fed clam flesh totalling 5%, 10%, or 20% of their body weight there was a step-wise increase in the scope, time to peak oxygen consumption, duration of the response and total SDA. The change in the rate of oxygen consumption was slower than other organisms, and oxygen uptake remained elevated for over 12d following consumption of the largest meal. There were also differences in the characteristics of the SDA if sunflower stars consumed a whole clam versus the shucked flesh of a clam. The time to reach peak oxygen consumption was greater for sunflower stars consuming a whole clam. This occurred because the clam had to be opened before they could digest the flesh; a smaller initial peak comprising 3.5% of the total SDA represented the energy require to open the clam valves. When the sunflower stars were fed different prey items (e.g. butter clam, purple urchin and herring) of similar wet organic mass, there was no difference in the time to peak, peak oxygen uptake or total SDA despite the fact that the prey items differed in protein, lipid and caloric content. There was an increased duration for which oxygen uptake remained elevated for sea stars that consumed the urchin meal. Five of the seven sunflower stars that consumed urchins exhibited a smaller second peak in oxygen uptake, totalling approximately 8.5% of the SDA energy budget. This likely represented the energy required to eject the urchin test from the stomach. Although the sunflower star is much larger and more active than other sea stars, it displayed similar SDA responses to other members of the Asteroidea, indicative of the low metabolic rate of this class.

  1. 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.

  2. Genotoxic potential of glyphosate formulations: mode-of-action investigations.

    PubMed

    Heydens, William F; Healy, Charles E; Hotz, Kathy J; Kier, Larry D; Martens, Mark A; Wilson, Alan G E; Farmer, Donna R

    2008-02-27

    A broad array of in vitro and in vivo assays has consistently demonstrated that glyphosate and glyphosate-containing herbicide formulations (GCHF) are not genotoxic. Occasionally, however, related and contradictory data are reported, including findings of mouse liver and kidney DNA adducts and damage following intraperitoneal (ip) injection. Mode-of-action investigations were therefore undertaken to determine the significance of these contradictory data while concurrently comparing results from ip and oral exposures. Exposure by ip injection indeed produced marked hepatic and renal toxicity, but oral administration did not. The results suggest that ip injection of GCHF may induce secondary effects mediated by local toxicity rather than genotoxicity. Furthermore, these results continue to support the conclusion that glyphosate and GCHF are not genotoxic under exposure conditions that are relevant to animals and humans.

  3. Neuroactive steroids have multiple actions to potentiate GABAA receptors.

    PubMed

    Akk, Gustav; Bracamontes, John R; Covey, Douglas F; Evers, Alex; Dao, Tim; Steinbach, Joe Henry

    2004-07-01

    The effects of neuroactive steroids on the function of GABAA receptors were studied using cell-attached records of single channel activity recorded from HEK293 cells transfected with alpha1 beta2 gamma2L subunits. Activity was elicited with a half-maximal (50 microM) concentration of GABA. Two steroids were studied in detail: ACN ((3alpha,5alpha,17beta)-3-hydroxyandrostane-17-carbonitrile) and B285 ((3alpha,5beta,17beta)-3-hydroxy-18-norandrostane-17-carbonitrile). Four effects on channel activity were seen, two on open time distributions and two on closed times. When clusters of openings were elicited in the absence of steroid, the open time distribution contained three components. ACN produced concentration-dependent alterations in the open time distribution. The prevalence of the longest duration class of open times was increased from about 15% to about 40% (EC50 about 180 nM ACN), while the duration of the longest class increased from 7.4 ms to 27 ms (EC50 about 35 nM ACN). B285 also increased the prevalence of the longest duration open times (EC50 about 18 nM B285) but increased the duration only at concentrations close to 10 microM. The differences in the actions of these two steroids suggest that the effects on proportion and duration of the long duration open time component are produced by independent mechanisms and that there are separate recognition sites for the steroids which are associated with the two functional actions. The closed time distributions also showed three components in the absence of steroid. The rate of occurrence of the two brief duration closed time components decreased with increasing ACN, with an EC50 of about 50 nM ACN. In contrast, B285 did not reduce the rate of occurrence of the brief closings until high concentrations were applied. However, both B285 and ACN reduced the rate of occurrence of the activation-related closed state selectively, with comparable IC50 concentrations (about 40 nM ACN, 20 nM B285). As in the case for

  4. Action potential initiation and propagation in CA3 pyramidal axons.

    PubMed

    Meeks, Julian P; Mennerick, Steven

    2007-05-01

    Thin, unmyelinated axons densely populate the mammalian hippocampus and cortex. However, the location and dynamics of spike initiation in thin axons remain unclear. We investigated basic properties of spike initiation and propagation in CA3 neurons of juvenile rat hippocampus. Sodium channel alpha subunit distribution and local applications of tetrodotoxin demonstrate that the site of first threshold crossing in CA3 neurons is approximately 35 microm distal to the soma, somewhat more proximal than our previous estimates. This discrepancy can be explained by the finding, obtained with simultaneous whole cell somatic and extracellular axonal recordings, that a zone of axon stretching to approximately 100 microm distal to the soma reaches a maximum rate of depolarization nearly synchronously by the influx of sodium from the high-density channels. Models of the proximal axon incorporating observed distributions of sodium channel staining recapitulated salient features of somatic and axonal spike waveforms, including the predicted initiation zone, characteristic spike latencies, and conduction velocity. The preferred initiation zone was unaltered by stimulus strength or repetitive spiking, but repetitive spiking increased threshold and significantly slowed initial segment recruitment time and conduction velocity. Our work defines the dynamics of initiation and propagation in hippocampal principal cell axons and may help reconcile recent controversies over initiation site in other axons.

  5. 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

  6. 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

  7. Calcium-Activated Chloride Channels (CaCCs) Regulate Action Potential and Synaptic Response in Hippocampal Neurons

    PubMed Central

    Huang, Wendy C.; Xiao, Shaohua; Huang, Fen; Harfe, Brian D.; Jan, Yuh Nung; Jan, Lily Yeh

    2012-01-01

    SUMMARY Central neurons respond to synaptic inputs from other neurons by generating synaptic potentials. Once the summated synaptic potentials reach threshold for action potential firing, the signal propagates leading to transmitter release at the synapse. The calcium influx accompanying such signaling opens calcium-activated ion channels for feedback regulation. Here we report a novel mechanism for modulating hippocampal neuronal signaling that involves calcium-activated chloride channels (CaCCs). We present the first evidence that CaCCs reside in hippocampal neurons and are in close proximity of calcium channels and NMDA receptors to shorten action potential duration, dampen excitatory synaptic potentials, impede temporal summation, and raise the threshold for action potential generation by synaptic potential. Having recently identified TMEM16A and TMEM16B as CaCCs, we further show that TMEM16B but not TMEM16A is important for hippocampal CaCC, laying the groundwork for deciphering the dynamic CaCC modulation of neuronal signaling in neurons important for learning and memory. PMID:22500639

  8. Attention and Memory for Faces and Actions in Infancy: The Salience of Actions over Faces in Dynamic Events.

    ERIC Educational Resources Information Center

    Bahrick, Lorraine E.; Gogate, Lakshmi J.; Ruiz, Ivonne

    2002-01-01

    Three experiments investigated discrimination and memory of 5.5-month-olds for videotapes of women performing different activities (blowing bubbles, brushing hair, brushing teeth) or static displays after a 1-minute and a 7-week delay. Findings demonstrate the attentional salience of actions over faces in dynamic events to 5.5-month-olds. Findings…

  9. Sources of Information for Discriminating Dynamic Human Actions

    ERIC Educational Resources Information Center

    Loucks, Jeff; Baldwin, Dare

    2009-01-01

    Despite the importance of action identification and discrimination in action perception and social cognition more broadly, little research has investigated how these processes are achieved. To this end, we sought to identify the extent to which adults capitalize on featural versus configural sources of information when discriminating small-scale…

  10. Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome

    NASA Astrophysics Data System (ADS)

    Kandori, Akihiko; Shimizu, Wataru; Yokokawa, Miki; Kamakura, Shiro; Miyatake, Kunio; Murakami, Masahiro; Miyashita, Tsuyoshi; Ogata, Kuniomi; Tsukada, Keiji

    2004-05-01

    A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution—plotted as a current-arrow map (CAM)—calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter.

  11. Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons

    PubMed Central

    Lee, Philip R.; Cohen, Jonathan E.; Iacobas, Dumitru A.; Iacobas, Sanda; Fields, R. Douglas

    2017-01-01

    Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life. PMID:28256583

  12. Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons.

    PubMed

    Lee, Philip R; Cohen, Jonathan E; Iacobas, Dumitru A; Iacobas, Sanda; Fields, R Douglas

    2017-03-03

    Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life.

  13. Mathematical Distinction in Action Potential between Primo-Vessels and Smooth Muscle

    PubMed Central

    Cho, Seong-Jin; Lee, Sang-Hun; Zhang, Wenji; Lee, Sae-Bhom; Choi, Kwang-Ho; Choi, Sun-Mi; Ryu, Yeon-Hee

    2012-01-01

    We studied the action potential of Primo-vessels in rats to determine the electrophysiological characteristics of these structures. We introduced a mathematical analysis method, a normalized Fourier transform that displays the sine and cosine components separately, to compare the action potentials of Primo-vessels with those for the smooth muscle. We found that Primo-vessels generated two types of action potential pulses that differed from those of smooth muscle: (1) Type I pulse had rapid depolarizing and repolarizing phases, and (2) Type II pulse had a rapid depolarizing phase and a gradually slowing repolarizing phase. PMID:22319544

  14. Evolutionary dynamics of collective action in spatially structured populations.

    PubMed

    Peña, Jorge; Nöldeke, Georg; Lehmann, Laurent

    2015-10-07

    Many models proposed to study the evolution of collective action rely on a formalism that represents social interactions as n-player games between individuals adopting discrete actions such as cooperate and defect. Despite the importance of spatial structure in biological collective action, the analysis of n-player games games in spatially structured populations has so far proved elusive. We address this problem by considering mixed strategies and by integrating discrete-action n-player games into the direct fitness approach of social evolution theory. This allows to conveniently identify convergence stable strategies and to capture the effect of population structure by a single structure coefficient, namely, the pairwise (scaled) relatedness among interacting individuals. As an application, we use our mathematical framework to investigate collective action problems associated with the provision of three different kinds of collective goods, paradigmatic of a vast array of helping traits in nature: "public goods" (both providers and shirkers can use the good, e.g., alarm calls), "club goods" (only providers can use the good, e.g., participation in collective hunting), and "charity goods" (only shirkers can use the good, e.g., altruistic sacrifice). We show that relatedness promotes the evolution of collective action in different ways depending on the kind of collective good and its economies of scale. Our findings highlight the importance of explicitly accounting for relatedness, the kind of collective good, and the economies of scale in theoretical and empirical studies of the evolution of collective action.

  15. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential

    NASA Astrophysics Data System (ADS)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    Objective. The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Approach. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Main results. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. Significance. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  16. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    PubMed

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

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  17. Nonlinear dynamics of skin potentials in the electrosensory paddlefish

    NASA Astrophysics Data System (ADS)

    Hofmann, Michael H.; Wilkens, Lon A.

    2011-12-01

    It is known that steady skin potentials are present in fishes due to chloride pumps in the gills and in the skin. We have found previously that these skin potentials can fluctuate and oscillate in the electrosensory paddlefish. Here we show that larger, discharge like potentials can be triggered by applying external electric fields in the water surrounding the fish. These resemble action potentials in nerve cells, but have a longer time scale. Like action potentials, these discharges travel laterally in the skin. They start at the tip of the rostrum and propagate caudally to the tip of the gill covers. They follow the all-or-nothing rule and need some refractory period before they can be evoked again. This is the first time that such discharges, so strikingly similar to action potentials, have been described at the level of a whole organism.

  18. Inhibition Potentiates the Synchronizing Action of Electrical Synapses

    PubMed Central

    Pfeuty, Benjamin; Golomb, David; Mato, Germán; Hansel, David

    2007-01-01

    In vivo and in vitro experimental studies have found that blocking electrical interactions connecting GABAergic interneurons reduces oscillatory activity in the γ range in cortex. However, recent theoretical works have shown that the ability of electrical synapses to promote or impede synchrony, when alone, depends on their location on the dendritic tree of the neurons, the intrinsic properties of the neurons and the connectivity of the network. The goal of the present paper is to show that this versatility in the synchronizing ability of electrical synapses is greatly reduced when the neurons also interact via inhibition. To this end, we study a model network comprising two-compartment conductance-based neurons interacting with both types of synapses. We investigate the effect of electrical synapses on the dynamical state of the network as a function of the strength of the inhibition. We find that for weak inhibition, electrical synapses reinforce inhibition-generated synchrony only if they promote synchrony when they are alone. In contrast, when inhibition is sufficiently strong, electrical synapses improve synchrony even if when acting alone they would stabilize asynchronous firing. We clarify the mechanism underlying this cooperative interplay between electrical and inhibitory synapses. We show that it is relevant in two physiologically observed regimes: spike-to-spike synchrony, where neurons fire at almost every cycle of the population oscillations, and stochastic synchrony, where neurons fire irregularly and at a rate which is substantially lower than the frequency of the global population rhythm. PMID:18946530

  19. Press to grasp: how action dynamics shape object categorization.

    PubMed

    Triberti, Stefano; Repetto, Claudia; Costantini, Marcello; Riva, Giuseppe; Sinigaglia, Corrado

    2016-03-01

    Action and object are deeply linked to each other. Not only can viewing an object influence an ongoing action, but motor representations of action can also influence visual categorization of objects. It is tempting to assume that this influence is effector-specific. However, there is indirect evidence suggesting that this influence may be related to the action goal and not just to the effector involved in achieving it. This paper aimed, for the first time, to tackle this issue directly. Participants were asked to categorize different objects in terms of the effector (e.g. hand or foot) typically used to act upon them. The task was delivered before and after a training session in which participants were instructed either just to press a pedal with their foot or to perform the same foot action with the goal of guiding an avatar's hand to grasp a small ball. Results showed that pressing a pedal to grasp a ball influenced how participants correctly identified graspable objects as hand-related ones, making their responses more uncertain than before the training. Just pressing a pedal did not have any similar effect. This is evidence that the influence of action on object categorization can be goal-related rather than effector-specific.

  20. Antioxidant properties of melatonin and its potential action in diseases.

    PubMed

    Karaaslan, Cigdem; Suzen, Sibel

    2015-01-01

    In recent years, relationship between free radicals and oxidative stress with aging, cancer, atherosclerosis, neurodegenerative disorders, diabetes, and inflammatory diseases became increasingly clear. Confirming the role of oxidants in numerous pathological conditions such as cancer, the antioxidants developed as therapeutics have been proven ineffective. It is well established that melatonin (MLT) and its metabolites are able to function as endogenous free-radical scavengers and broadspectrum antioxidants. Numerous studies also proved the role of MLT and its derivatives in many physiological processes and therapeutic functions, such as the regulation of circadian rhythm and immune functions. The aim of this review is to arouse attention to MLT as a potentially valuable agent in the prevention and/or treatment of some diseases.

  1. Wheel-running exercise alters rat diaphragm action potentials and their regulation by K+ channels.

    PubMed

    Van Lunteren, Erik; Moyer, Michelle

    2003-08-01

    Endurance exercise modifies regulatory systems that control skeletal muscle Na+ and K+ fluxes, in particular Na+-K+-ATPase-mediated transport of these ions. Na+ and K+ ion channels also play important roles in the regulation of ionic movements, specifically mediating Na+ influx and K+ efflux that occur during contractions resulting from action potential depolarization and repolarization. Whether exercise alters skeletal muscle electrophysiological properties controlled by these ion channels is unclear. The present study tested the hypothesis that endurance exercise modifies diaphragm action potential properties. Exercised rats spent 8 wk with free access to running wheels, and they were compared with sedentary rats living in conventional rodent housing. Diaphragm muscle was subsequently removed under anesthesia and studied in vitro. Resting membrane potential was not affected by endurance exercise. Muscle from exercised rats had a slower rate of action potential repolarization than that of sedentary animals (P = 0.0098), whereas rate of depolarization was similar in the two groups. The K+ channel blocker 3,4-diaminopyridine slowed action potential repolarization and increased action potential area of both exercised and sedentary muscle. However, these effects were significantly smaller in diaphragm from exercised than sedentary rats. These data indicate that voluntary running slows diaphragm action potential repolarization, most likely by modulating K+ channel number or function.

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

    PubMed

    deCharms, R C; Merzenich, M M

    1996-06-13

    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 synchronized, which could be involved in 'binding' together individual firing-rate feature representations into a unified object percept. 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 systemically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.

  3. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy.

    PubMed

    Kole, Maarten H P; Letzkus, Johannes J; Stuart, Greg J

    2007-08-16

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

  4. Pharmacological actions and potential uses of Momordica charantia: a review.

    PubMed

    Grover, J K; Yadav, S P

    2004-07-01

    Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in last few decades has certified several such claims of use of several plants of traditional medicine. Popularity of Momordica charantia (MC) in various systems of traditional medicine for several ailments (antidiabetic, abortifacient, anthelmintic, contraceptive, dysmenorrhea, eczema, emmenagogue, antimalarial, galactagogue, gout, jaundice, abdominal pain, kidney (stone), laxative, leprosy, leucorrhea, piles, pneumonia, psoriasis, purgative, rheumatism, fever and scabies) focused the investigator's attention on this plant. Over 100 studies using modern techniques have authenticated its use in diabetes and its complications (nephropathy, cataract, insulin resistance), as antibacterial as well as antiviral agent (including HIV infection), as anthelmintic and abortifacient. Traditionally it has also been used in treating peptic ulcers, interestingly in a recent experimental studies have exhibited its potential against Helicobacter pylori. Most importantly, the studies have shown its efficacy in various cancers (lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and Hodgkin's disease). There are few reports available on clinical use of MC in diabetes and cancer patients that have shown promising results.

  5. Epidermal Laser Stimulation of Action Potentials in the Frog Sciatic Nerve

    DTIC Science & Technology

    2008-10-01

    Laser Stimulation of Action Potentials in the Frog Sciatic Nerve Nichole M. Jindra Robert J. Thomas Human Effectiveness Directorate Directed...in the Frog Sciatic Nerve 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62202F 6. AUTHOR(S) .Nichole M. Jindra, Robert J. Thomas, Douglas N...Alan Rice 14. ABSTRACT Measurements of laser stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) were made using

  6. Uniform Action Potential Repolarization within the Sarcolemma of In Situ Ventricular Cardiomyocytes

    PubMed Central

    Bu, Guixue; Adams, Heather; Berbari, Edward J.; Rubart, Michael

    2009-01-01

    Previous studies have speculated, based on indirect evidence, that the action potential at the transverse (t)-tubules is longer than at the surface membrane in mammalian ventricular cardiomyocytes. To date, no technique has enabled recording of electrical activity selectively at the t-tubules to directly examine this hypothesis. We used confocal line-scan imaging in conjunction with the fast response voltage-sensitive dyes ANNINE-6 and ANNINE-6plus to resolve action potential-related changes in fractional dye fluorescence (ΔF/F) at the t-tubule and surface membranes of in situ mouse ventricular cardiomyocytes. Peak ΔF/F during action potential phase 0 depolarization averaged −21% for both dyes. The shape and time course of optical action potentials measured with the water-soluble ANNINE-6plus were indistinguishable from those of action potentials recorded with intracellular microelectrodes in the absence of the dye. In contrast, optical action potentials measured with the water-insoluble ANNINE-6 were significantly prolonged compared to the electrical recordings obtained from dye-free hearts, suggesting electrophysiological effects of ANNINE-6 and/or its solvents. With either dye, the kinetics of action potential-dependent changes in ΔF/F during repolarization were found to be similar at the t-tubular and surface membranes. This study provides what to our knowledge are the first direct measurements of t-tubule electrical activity in ventricular cardiomyocytes, which support the concept that action potential duration is uniform throughout the sarcolemma of individual cells. PMID:19289075

  7. Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals.

    PubMed

    Jackson, M B; Konnerth, A; Augustine, G J

    1991-01-15

    Hormone release from nerve terminals in the neurohypophysis is a sensitive function of action potential frequency. We have investigated the cellular mechanisms responsible for this frequency-dependent facilitation by combining patch clamp and fluorimetric Ca2+ measurements in single neurosecretory terminals in thin slices of the rat posterior pituitary. In these terminals both action potential-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) and action potential duration were enhanced by high-frequency stimuli, all with a frequency dependence similar to that of hormone release. Furthermore, brief voltage clamp pulses inactivated a K+ current with a very similar frequency dependence. These results support a model for frequency-dependent facilitation in which the inactivation of a K+ current broadens action potentials, leading to an enhancement of [Ca2+]i signals. Further experiments tested for a causal relationship between action potential broadening and facilitation of [Ca2+]i changes. First, increasing the duration of depolarization, either by broadening action potentials with the K(+)-channel blocker tetraethylammonium or by applying longer depolarizing voltage clamp steps, increased [Ca2+]i changes. Second, eliminating frequency-dependent changes in duration, by voltage clamping the terminal with constant duration pulses, substantially reduced the frequency-dependent enhancement of [Ca2+]i changes. These results indicate that action potential broadening contributes to frequency-dependent facilitation of [Ca2+]i changes. However, the small residual frequency dependence of [Ca2+]i changes seen with constant duration stimulation suggests that a second process, distinct from action potential broadening, also contributes to facilitation. These two frequency-dependent mechanisms may also contribute to activity-dependent plasticity in synaptic terminals.

  8. Modeling of action potential generation in NG108-15 cells.

    PubMed

    Molnar, Peter; Hickman, James J

    2014-01-01

    In order to explore the possibility of identifying toxins based on their effect on the shape of action potentials, we created a computer model of the action potential generation in NG108-15 cells (a neuroblastoma/glioma hybrid cell line). To generate the experimental data for model validation, voltage-dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated using the Hodgkin-Huxley formalism and were fitted to the recorded action potentials. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently, and their respective effects were identified based on the predicted changes in the fitted parameters.

  9. Effects of sparfloxacin, grepafloxacin, moxifloxacin, and ciprofloxacin on cardiac action potential duration.

    PubMed

    Patmore, L; Fraser, S; Mair, D; Templeton, A

    2000-10-20

    Fluoroquinolone antibiotics have been associated with QT prolongation following administration to humans. This study compares the effects of four fluoroquinolones, sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin on action potential duration recorded from canine isolated cardiac Purkinje fibres. Left and right ventricular Purkinje fibres were isolated from canine hearts and continuously superfused with physiological salt solution. Action potential duration at 90% repolarization was recorded via intracellular microelectrodes. Sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin prolonged action potential duration in a concentration dependent manner. Mean concentrations causing a 15% prolongation of action potential duration recorded at a stimulation frequency of 1 Hz were: sparfloxacin 4.2+/-0.7 microg/ml; grepafloxacin 9.3+/-0.9 microg/ml; moxifloxacin 9.9+/-1.6 microg/ml and ciprofloxacin 72.8+/-26.4 microg/ml. Prolongation was inverse frequency dependent with larger increases in action potential duration occurring when the stimulation frequency was reduced to 0.5 Hz. These results indicate that effects on action potential duration vary within this class of compound. Rank order of potency was sparfloxacin > grepafloxacin = moxifloxacin > ciprofloxacin.

  10. 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.

  11. Generalized sigma model with dynamical antisymplectic potential and non-Abelian de Rham's differential

    NASA Astrophysics Data System (ADS)

    Batalin, Igor A.; Lavrov, Peter M.

    2017-04-01

    For topological sigma models, we propose that their local Lagrangian density is allowed to depend non-linearly on the de Rham's "velocities" DZA. Then, by differentiating the Lagrangian density with respect to the latter de Rham's "velocities", we define a "dynamical" anti-symplectic potential, in terms of which a "dynamical" anti-symplectic metric is defined, as well. We define the local and the functional antibracket via the dynamical anti-symplectic metric. Finally, we show that the generalized action of the sigma model satisfies the functional master equation, as required.

  12. The unifying role of dissipative action in the dynamic failure of solids

    SciTech Connect

    Grady, Dennis

    2015-05-19

    Dissipative action, the product of dissipation energy and transport time, is fundamental to the dynamic failure of solids. Invariance of the dissipative action underlies the fourth-power nature of structured shock waves observed in selected solid metals and compounds. Dynamic failure through shock compaction, tensile spall and adiabatic shear are also governed by a constancy of the dissipative action. This commonality underlying the various modes of dynamic failure is described and leads to deeper insights into failure of solids in the intense shock wave event. These insights are in turn leading to a better understanding of the shock deformation processes underlying the fourth-power law. Experimental result and material models encompassing the dynamic failure of solids are explored for the purpose of demonstrating commonalities leading to invariance of the dissipation action. As a result, calculations are extended to aluminum and uranium metals with the intent of predicting micro-scale energetics and spatial scales in the structured shock wave.

  13. Potential Competitive Dynamics of Acoustic Ecology.

    PubMed

    Radford, C A; Montgomery, J C

    2016-01-01

    The top predators in coastal marine ecosystems, such as whales, dolphins, seabirds, and large predatory fishes (including sharks), may compete with each other to exploit food aggregations. Finding these patchy food sources and being first to a food patch could provide a significant competitive advantage. Our hypothesis is that food patches have specific sound signatures that marine predators could detect and that acoustic sources and animal sensory capabilities may contribute to competition dynamics. Preliminary analysis shows that diving gannets have a distinct spectral signature between 80 and 200 Hz, which falls within the hearing sensitivity of large pelagic fishes. Therefore, we suggest that diving birds may contribute to the sound signatures of food aggregations, linking competition dynamics both above and below the water surface.

  14. Dynamic Simulation and Static Matching for Action Prediction: Evidence from Body Part Priming

    ERIC Educational Resources Information Center

    Springer, Anne; Brandstadter, Simone; Prinz, Wolfgang

    2013-01-01

    Accurately predicting other people's actions may involve two processes: internal real-time simulation (dynamic updating) and matching recently perceived action images (static matching). Using a priming of body parts, this study aimed to differentiate the two processes. Specifically, participants played a motion-controlled video game with…

  15. The Adiabatic Invariance of the Action Variable in Classical Dynamics

    ERIC Educational Resources Information Center

    Wells, Clive G.; Siklos, Stephen T. C.

    2007-01-01

    We consider one-dimensional classical time-dependent Hamiltonian systems with quasi-periodic orbits. It is well known that such systems possess an adiabatic invariant which coincides with the action variable of the Hamiltonian formalism. We present a new proof of the adiabatic invariance of this quantity and illustrate our arguments by means of…

  16. Video Game Learning Dynamics: Actionable Measures of Multidimensional Learning Trajectories

    ERIC Educational Resources Information Center

    Reese, Debbie Denise; Tabachnick, Barbara G.; Kosko, Robert E.

    2015-01-01

    Valid, accessible, reusable methods for instructional video game design and embedded assessment can provide actionable information enhancing individual and collective achievement. Cyberlearning through game-based, metaphor-enhanced learning objects (CyGaMEs) design and embedded assessment quantify player behavior to study knowledge discovery and…

  17. Temporal Dynamics of Action Contribution to Object Categorization

    ERIC Educational Resources Information Center

    Gonzalez Perilli, Fernando; Barrada, Juan Ramon; Maiche, Alejandro

    2013-01-01

    The presentation of a hand grasp facilitates the recognition of subsequent objects when the grasp is coherent with the object to be identified. This outcome is usually explained as the integration of two different processes: descriptive visual processes in ventral visual areas and processes in charge of the computations of action metrics in dorsal…

  18. Action principles for hydro- and thermo-dynamics

    NASA Astrophysics Data System (ADS)

    Fronsdal, Christian

    2017-03-01

    For all its brilliant success stories, theoretical physics is actually in a lamentable state. The best way to highlight the situation and at the same time point out that it is not difficult to do better — using action principles — is to present several examples.

  19. Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism.

    PubMed

    Ahmed, Zaghloul; Wieraszko, Andrzej

    2015-07-01

    This paper investigates the influence of pulsed magnetic fields (PMFs) on amplitude of evoked, compound action potential (CAP) recorded from the segments of sciatic nerve in vitro. PMFs were applied for 30 min at frequency of 0.16 Hz and intensity of 15 mT. In confirmation of our previous reports, PMF exposure enhanced amplitude of CAPs. The effect persisted beyond PMF activation period. As expected, CAP amplitude was attenuated by antagonists of sodium channel, lidocaine, and tetrodotoxin. Depression of the potential by sodium channels antagonists was reversed by subsequent exposure to PMFs. The effect of elevated potassium concentration and veratridine on the action potential was modified by exposure to PMFs as well. Neither inhibitors of protein kinase C and protein kinase A, nor known free radicals scavengers had any effects on PMF action. Possible mechanisms of PMF action are discussed.

  20. Direct depolarization and antidromic action potentials transiently suppress dendritic IPSPs in hippocampal CA1 pyramidal cells.

    PubMed

    Morishita, W; Alger, B E

    2001-01-01

    Whole-cell current-clamp recordings were made from distal dendrites of rat hippocampal CA1 pyramidal cells. Following depolarization of the dendritic membrane by direct injection of current pulses or by back-propagating action potentials elicited by antidromic stimulation, evoked gamma-aminobutyric acid-A (GABA(A)) receptor-mediated inhibitory postsynaptic potentials (IPSPs) were transiently suppressed. This suppression had properties similar to depolarization-induced suppression of inhibition (DSI): it was enhanced by carbachol, blocked by dendritic hyperpolarization sufficient to prevent action potential invasion, and reduced by 4-aminopyridine (4-AP) application. Thus DSI or a DSI-like process can be recorded in CA1 distal dendrites. Moreover, localized application of TTX to stratum pyramidale blocked somatic action potentials and somatic IPSPs, but not dendritic IPSPs or DSI induced by direct dendritic depolarization, suggesting DSI is expressed in part in the dendrites. These data extend the potential physiological roles of DSI.

  1. The Flash-Triggering Action Potential of the Luminescent Dinoflagellate Noctiluca

    PubMed Central

    Eckert, Roger; Sibaoka, Takao

    1968-01-01

    The action potential which elicits luminescence in Noctiluca is recorded from the flotation vacuole as a transient all-or-none hyperpolarization in response to either local or general application of inward (bath to vacuole) current. Experiments were performed to determine whether the unorthodox polarities of both the stimulus current and the potential response resulted from uncommon bioelectric mechanisms or from special morphological features of this species. The findings all indicate that the action potential belongs to the familiar class of responses which have their origin in voltage- and time-dependent selective increases in membrane permeability, and that morphological factors account for the observed deviations from normal behavior. Both the stimulus and the response have orthodox polarities provided the vacuole is designated as an "external" extracytoplasmic compartment. Differential recording between vacuole and cytoplasm showed that the action potential occurs across the vacuolar membrane, with the cytoplasmic potential, which at rest is negative with respect to the vacuole, overshooting zero and reversing sign to become transiently electropositive. The rising phase of the action potential therefore depends on active current flow through the vacuolar membrane from the vacuole into the cytoplasm. Propagation of the action potential over the subspherical cell from the locus of stimulation is thought to depend largely on the core conductor properties of the thin perivacuolar shell of cytoplasm which is bounded on its inner surface by the excitable membrane and on its outer surface by inexcitable membranes. PMID:5672004

  2. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    PubMed

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  3. Cellular uncoupling can unmask dispersion of action potential duration in ventricular myocardium. A computer modeling study.

    PubMed

    Lesh, M D; Pring, M; Spear, J F

    1989-11-01

    Although slow conduction is a requirement for the preparation of sustained reentry, it alone is not sufficient for the initiation of reentry. Additionally, unidirectional block and recovery of excitability distal to the site of block must occur. Thus, a comprehensive description of the electrophysiological determinants of reentry must explain both slow conduction and unidirectional block. Although there is a growing body of research exploring the influence of axial resistivity and anisotropy on slow conduction, somewhat less is known about the relation of axial resistivity to spatial dispersion of action potential duration, a condition favorable to the development of unidirectional block. We hypothesized that when cells are well coupled, local differences in intrinsic action potential duration are not evident and that, as axial resistivity increases, local variation in action potential duration becomes manifest. We tested this hypothesis in a numerical model of electrical propagation in a grid of resistively coupled ionic current sources simulating a sheet of ventricular myocardium. Spatial dispersion of intrinsic action potential duration was simulated by varying the magnitude of the fully activated slow inward conductance in Beeler-Reuter membrane ionic kinetics. By then altering coupling resistance, we showed that dispersion of manifest action potential duration is masked in the setting of normal low-resistance cellular coupling and unmasked by increased axial resistance. When nonuniform anisotropy was simulated, dramatic pacing-site-dependent changes in both the pattern of activation and dispersion of action potential duration were noted. These findings may be important in understanding the mechanism of reentrant tachycardia initiation in the border zone of chronic, healed myocardial infarctions where evidence suggests that abnormal cellular coupling is the predominant electrophysiological derangement. In this study, we have shown, using a detailed ionic

  4. Active action potential propagation but not initiation in thalamic interneuron dendrites

    PubMed Central

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  5. Effect of an educational game on university students' learning about action potentials.

    PubMed

    Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K

    2017-06-01

    The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na(+)-K(+)-ATPase pump. During the game activity, the students arranged the pieces to demonstrate how the ions move through the membrane in a resting state and during an action potential, linking the ion movement with a graph of the action potential. To test the effect of the game activity on student understanding, first-year dental students were given the game to play at different times in a series of classes teaching resting membrane potential and action potentials. In all experiments, students who played the game performed better in assessments. According to 98% of the students, the game supported the learning process. The data confirm the students' perception, indicating that the educational game improved their understanding about action potentials.

  6. Extracellular calcium transients and action potential configuration changes related to post-stimulatory potentiation in rabbit atrium.

    PubMed

    Hilgemann, D W

    1986-05-01

    Extracellular calcium transients were monitored with 2 mM tetramethylmurexide at low calcium (250 microM total, 130 microM free), and action potentials were monitored together with developed tension at normal calcium (1.3 mM) during the production and decay of post-stimulatory potentiation in rabbit left atrial strips. At normal calcium, the contractile potentiation produced by a brief burst of 4 Hz stimulation is lost in three to five post-stimulatory excitations, which correlate with a negative staircase of the late action potential. At low calcium, stimulation at 4 Hz for 3-8 s results in a net extracellular calcium depletion of 5-15 microM. At the subsequent potentiated contraction (1-45 s rest), total extracellular calcium increases by 4-8 microM. The contractile response at a second excitation is greatly suppressed and results in little or no further calcium shift; the sequence can be repeated immediately thereafter. Reducing external sodium to 60 mM (sucrose replacement) enhances post-rest contractions, suppresses the late action potential, nearly eliminates loss of contractility and net calcium efflux at post-rest excitations, and markedly reduces extracellular calcium depletion during rapid stimulation. 4-Aminopyridine (1 mM) markedly suppresses the rapid early repolarization of this preparation at post-rest excitations and the loss of contractility at post-rest stimulation from the rested state; during a post-stimulatory potentiation sequence at low calcium, replenishment of extracellular calcium takes several post-stimulatory excitations. Ryanodine (10 nM to 5 microM) abolishes the post-stimulatory contraction at rest periods of greater than 5 s. If the initial repolarization is rapid, ryanodine suppresses the late action potential, calcium efflux during quiescence is greatly accelerated, and subsequent excitations do not result in an accumulation of extracellular calcium. A positive staircase of the early action potential correlates with the magnitude

  7. Verbal Synchrony and Action Dynamics in Large Groups.

    PubMed

    von Zimmermann, Jorina; Richardson, Daniel C

    2016-01-01

    While synchronized movement has been shown to increase liking and feelings of togetherness between people, we investigated whether collective speaking in time would change the way that larger groups played a video game together. Anthropologists have speculated that the function of interpersonal coordination in dance, chants, and singing is not just to produce warm, affiliative feelings, but also to improve group action. The group that chants and dances together hunts well together. Direct evidence for this is sparse, as research so far has mainly studied pairs, the effects of coordinated physical movement, and measured cooperation and affiliative decisions. In our experiment, large groups of people were given response handsets to play a computer game together, in which only joint coordinative efforts lead to success. Before playing, the synchrony of their verbal behavior was manipulated. After the game, we measured group members' affiliation toward their group, their performance on a memory task, and the way in which they played the group action task. We found that verbal synchrony in large groups produced affiliation, enhanced memory performance, and increased group members' coordinative efforts. Our evidence suggests that the effects of synchrony are stable across modalities, can be generalized to larger groups and have consequences for action coordination.

  8. Verbal Synchrony and Action Dynamics in Large Groups

    PubMed Central

    von Zimmermann, Jorina; Richardson, Daniel C.

    2016-01-01

    While synchronized movement has been shown to increase liking and feelings of togetherness between people, we investigated whether collective speaking in time would change the way that larger groups played a video game together. Anthropologists have speculated that the function of interpersonal coordination in dance, chants, and singing is not just to produce warm, affiliative feelings, but also to improve group action. The group that chants and dances together hunts well together. Direct evidence for this is sparse, as research so far has mainly studied pairs, the effects of coordinated physical movement, and measured cooperation and affiliative decisions. In our experiment, large groups of people were given response handsets to play a computer game together, in which only joint coordinative efforts lead to success. Before playing, the synchrony of their verbal behavior was manipulated. After the game, we measured group members’ affiliation toward their group, their performance on a memory task, and the way in which they played the group action task. We found that verbal synchrony in large groups produced affiliation, enhanced memory performance, and increased group members’ coordinative efforts. Our evidence suggests that the effects of synchrony are stable across modalities, can be generalized to larger groups and have consequences for action coordination. PMID:28082944

  9. Frequency-dependent action potential prolongation in Aplysia pleural sensory neurones.

    PubMed

    Edstrom, J P; Lukowiak, K D

    1985-10-01

    The effects of repetitive activity on action-potential shape in Aplysia californica pleural sensory cells are described. Action potentials were evoked by intracellular current injection at frequencies between 7.41 and 0.2 Hz. In contrast to other molluscan neurons having brief action potentials, it was found that at these firing rates the normally brief action potential develops a prominent shoulder or plateau during the repolarization phase. Higher stimulus rates broaden the action potential more rapidly and to a greater extent than lower stimulus rates. Inactivation is slow relative to activation; effects of 3-s 6-Hz trains are detectable after 1 min rest. The amplitude of the plateau voltage reaches a maximum of 50-70 mV at the highest stimulus rates tested. Frequency-dependent increases in action-potential duration measured at half-amplitude normally range between 6 and 15 ms. Cadmium, at concentrations between 0.05 and 0.5 mM, antagonizes frequency-dependent broadening. The increases in duration induced by repetitive activity are more sensitive to cadmium than are the increases in plateau amplitude. Tetraethylammonium, at concentrations between 0.5 and 10 mM, slightly increases the duration and amplitude of single action potentials. During repetitive activity at high stimulus rates the maximum duration and rate of broadening are both increased but the amplitude of the plateau potential is not affected by these tetraethylammonium concentrations. Above 10 mM, tetraethylammonium greatly increases the duration and amplitude of single action potentials as well as the rates of action-potential duration and amplitude increase during repetitive activity. These high tetraethylammonium concentrations also cause the normally smoothly increasing duration and amplitude to reach a maximum value early in a train and then decline slowly during the remainder of the train. The consequences of frequency-dependent spike broadening in these neurons have not yet been investigated

  10. Geostrophic Scatter Diagrams and Potential Vorticity Dynamics.

    NASA Astrophysics Data System (ADS)

    Read, P. L.; Rhines, P. B.; White, A. A.

    1986-12-01

    where S is the potential vorticity forcing, K the lateral eddy (or viscous) v the horizontal velocity, and the integrals are taken over and around any region enclosed by a mean streamline. Hence dQ/dis often negative. corresponding to two common properties of quasi-geostrophic circulations: that the eddy motion (or viscosity) transport Q down its mean gradient (K > 0) and that the circulation integral have the same sign as the potential vorticity forcing. Two sets of examples, both involving (Q,) scatter diagrams constructed from numerically simulated data, are presented. One relates to steady baroclinic wave motion in a rotating annulus system, and the other to the time-averaged circulation in an ocean basin.

  11. 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

    2015-02-03

    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.

  12. 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.

  13. Low Somatic Sodium Conductance Enhances Action Potential Precision in Time-Coding Auditory Neurons.

    PubMed

    Yang, Yang; Ramamurthy, Bina; Neef, Andreas; Xu-Friedman, Matthew A

    2016-11-23

    Auditory nerve fibers encode sounds in the precise timing of action potentials (APs), which is used for such computations as sound localization. Timing information is relayed through several cell types in the auditory brainstem that share an unusual property: their APs are not overshooting, suggesting that the cells have very low somatic sodium conductance (gNa). However, it is not clear how gNa influences temporal precision. We addressed this by comparing bushy cells (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have normal overshooting APs. BCs play a central role in both relaying and refining precise timing information from the auditory nerve, whereas SCs discard precise timing information and encode the envelope of sound amplitude. Nucleated-patch recording at near-physiological temperature indicated that the Na current density was 62% lower in BCs, and the voltage dependence of gNa inactivation was 13 mV hyperpolarized compared with SCs. We endowed BCs with SC-like gNa using two-electrode dynamic clamp and found that synaptic activity at physiologically relevant rates elicited APs with significantly lower probability, through increased activation of delayed rectifier channels. In addition, for two near-simultaneous synaptic inputs, the window of coincidence detection widened significantly with increasing gNa, indicating that refinement of temporal information by BCs is degraded by gNa Thus, reduced somatic gNa appears to be an adaption for enhancing fidelity and precision in time-coding neurons.

  14. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond

    PubMed Central

    Barry, John F.; Turner, Matthew J.; Schloss, Jennifer M.; Glenn, David R.; Song, Yuyu; Lukin, Mikhail D.; Park, Hongkun; Walsworth, Ronald L.

    2016-01-01

    Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution—e.g., magnetic resonance imaging methods and magnetoencephalography—or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector. PMID:27911765

  15. Multifocal Fluorescence Microscope for Fast Optical Recordings of Neuronal Action Potentials

    PubMed Central

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

    2015-01-01

    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 Ca2+ transients resulting from APs in neurons labeled with the Ca2+ 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

  16. Action potential generation in an anatomically constrained model of medial superior olive axons.

    PubMed

    Lehnert, Simon; Ford, Marc C; Alexandrova, Olga; Hellmundt, Franziska; Felmy, Felix; Grothe, Benedikt; Leibold, Christian

    2014-04-09

    Neurons in the medial superior olive (MSO) encode interaural time differences (ITDs) with sustained firing rates of >100 Hz. They are able to generate such high firing rates for several hundred milliseconds despite their extremely low-input resistances of only few megaohms and high synaptic conductances in vivo. The biophysical mechanisms by which these leaky neurons maintain their excitability are not understood. Since action potentials (APs) are usually assumed to be generated in the axon initial segment (AIS), we analyzed anatomical data of proximal MSO axons in Mongolian gerbils and found that the axon diameter is <1 μm and the internode length is ∼100 μm. Using a morphologically constrained computational model of the MSO axon, we show that these thin axons facilitate the excitability of the AIS. However, for ongoing high rates of synaptic inputs the model generates a substantial fraction of APs in its nodes of Ranvier. These distally initiated APs are mediated by a spatial gradient of sodium channel inactivation and a strong somatic current sink. The model also predicts that distal AP initiation increases the dynamic range of the rate code for ITDs.

  17. Action potential bursts enhance transmitter release at a giant central synapse.

    PubMed

    Zhang, Bo; Sun, Liang; Yang, Yi-Mei; Huang, Hong-Ping; Zhu, Fei-Peng; Wang, Li; Zhang, Xiao-Yu; Guo, Shu; Zuo, Pan-Li; Zhang, Claire X; Ding, Jiu-Ping; Wang, Lu-Yang; Zhou, Zhuan

    2011-05-01

    Patterns of action potentials (APs), often in the form of bursts, are critical for coding and processing information in the brain. However, how AP bursts modulate secretion at synapses remains elusive. Here, using the calyx of Held synapse as a model we compared synaptic release evoked by AP patterns with a different number of bursts while the total number of APs and frequency were fixed. The ratio of total release produced by multiple bursts to that by a single burst was defined as 'burst-effect'.We found that four bursts of 25 stimuli at 100 Hz increased the totalcharge of EPSCs to 1.47 ± 0.04 times that by a single burst of 100 stimuli at the same frequency.Blocking AMPA receptor desensitization and saturation did not alter the burst-effect, indicating that it was mainly determined by presynaptic mechanisms. Simultaneous dual recordings of presynaptic membrane capacitance (Cm) and EPSCs revealed a similar burst-effect, being 1.58±0.13by Cm and 1.49±0.05 by EPSCs. Reducing presynapticCa2+ influx by lowering extracellular Ca2+concentration or buffering residual intracellular Ca2+ with EGTA inhibited the burst-effect. We further developed a computational model largely recapitulating the burst-effect and demonstrated that this effect is highly sensitive to dynamic change in availability of the releasable pool of synaptic vesicles during various patterns of activities. Taken together, we conclude that AP bursts modulate synaptic output mainly through intricate interaction between depletion and replenishment of the large releasable pool. This burst-effect differs from the somatic burst-effect previously described from adrenal chromaffin cells, which substantially depends on activity-induced accumulation of Ca2+ to facilitate release of a limited number of vesicles in the releasable pool. Hence, AP bursts may play an important role in dynamically regulating synaptic strength and fidelity during intense neuronal activity at central synapses.

  18. Encoding of High Frequencies Improves with Maturation of Action Potential Generation in Cultured Neocortical Neurons

    PubMed Central

    Nikitin, Evgeny S.; Bal, Natalia V.; Malyshev, Aleksey; Ierusalimsky, Victor N.; Spivak, Yulia; Balaban, Pavel M.; Volgushev, Maxim

    2017-01-01

    The ability of neocortical neurons to detect and encode rapid changes at their inputs is crucial for basic neuronal computations, such as coincidence detection, precise synchronization of activity and spike-timing dependent plasticity. Indeed, populations of cortical neurons can respond to subtle changes of the input very fast, on a millisecond time scale. Theoretical studies and model simulations linked the encoding abilities of neuronal populations to the fast onset dynamics of action potentials (APs). Experimental results support this idea, however mechanisms of fast onset of APs in cortical neurons remain elusive. Studies in neuronal cultures, that are allowing for accurate control over conditions of growth and microenvironment during the development of neurons and provide better access to the spike initiation zone, may help to shed light on mechanisms of AP generation and encoding. Here we characterize properties of AP encoding in neocortical neurons grown for 11–25 days in culture. We show that encoding of high frequencies improves upon culture maturation, which is accompanied by the development of passive electrophysiological properties and AP generation. The onset of APs becomes faster with culture maturation. Statistical analysis using correlations and linear model approaches identified the onset dynamics of APs as a major predictor of age-dependent changes of encoding. Encoding of high frequencies strongly correlated also with the input resistance of neurons. Finally, we show that maturation of encoding properties of neurons in cultures is similar to the maturation of encoding in neurons studied in slices. These results show that maturation of AP generators and encoding is, to a large extent, determined genetically and takes place even without normal micro-environment and activity of the whole brain in vivo. This establishes neuronal cultures as a valid experimental model for studying mechanisms of AP generation and encoding, and their maturation. PMID

  19. Unmyelinated visceral afferents exhibit frequency dependent action potential broadening while myelinated visceral afferents do not.

    PubMed

    Li, Bai-Yan; Feng, Bin; Tsu, Hwa Y; Schild, John H

    2007-06-21

    Sensory information arising from visceral organ systems is encoded into action potential trains that propagate along afferent fibers to target nuclei in the central nervous system. These information streams range from tight patterns of action potentials that are well synchronized with the sensory transduction event to irregular, patternless discharge with no clear correlation to the sensory input. In general terms these afferent pathways can be divided into unmyelinated and myelinated fiber types. Our laboratory has a long standing interest in the functional differences between these two types of afferents in terms of the preprocessing of sensory information into action potential trains (synchrony, frequency, duration, etc.), the reflexogenic consequences of this sensory input to the central nervous system and the ionic channels that give rise to the electrophysiological properties of these unique cell types. The aim of this study was to determine whether there were any functional differences in the somatic action potential characteristics of unmyelinated and myelinated vagal afferents in response to different rates of sensory nerve stimulation. Our results showed that activity and frequency-dependent widening of the somatic action potential was quite prominent in unmyelinated but not myelinated vagal afferents. Spike broadening often leads to increased influx of Ca(2+) ions that has been associated with a diverse range of modulatory mechanisms both at the cell body and central synaptic terminations (e.g. increased neurotransmitter release.) We conclude that our observations are indicative of fundamentally different mechanisms for neural integration of sensory information arising from unmyelinated and myelinated vagal afferents.

  20. Axonal actin in action: Imaging actin dynamics in neurons.

    PubMed

    Ladt, Kelsey; Ganguly, Archan; Roy, Subhojit

    2016-01-01

    Actin is a highly conserved, key cytoskeletal protein involved in numerous structural and functional roles. In neurons, actin has been intensively investigated in axon terminals-growth cones-and dendritic spines, but details about actin structure and dynamics in axon shafts have remained obscure for decades. A major barrier in the field has been imaging actin. Actin exists as soluble monomers (G-actin) as well as actin filaments (F-actin), and labeling actin with conventional fluorescent probes like GFP/RFP typically leads to a diffuse haze that makes it difficult to discern kinetic behaviors. In a recent publication, we used F-actin selective probes to visualize actin dynamics in axons, resolving striking actin behaviors that have not been described before. However, using these probes to visualize actin dynamics is challenging as they can cause bundling of actin filaments; thus, experimental parameters need to be strictly optimized. Here we describe some practical methodological details related to using these probes for visualizing F-actin dynamics in axons.

  1. Dynamics of Representational Change: Entropy, Action, and Cognition

    ERIC Educational Resources Information Center

    Stephen, Damian G.; Dixon, James A.; Isenhower, Robert W.

    2009-01-01

    Explaining how the cognitive system can create new structures has been a major challenge for cognitive science. Self-organization from the theory of nonlinear dynamics offers an account of this remarkable phenomenon. Two studies provide an initial test of the hypothesis that the emergence of new cognitive structure follows the same universal…

  2. Frontal Oscillatory Dynamics Predict Feedback Learning and Action Adjustment

    ERIC Educational Resources Information Center

    van de Vijver, Irene; Ridderinkhof, K. Richard; Cohen, Michael X.

    2011-01-01

    Frontal oscillatory dynamics in the theta (4-8 Hz) and beta (20-30 Hz) frequency bands have been implicated in cognitive control processes. Here we investigated the changes in coordinated activity within and between frontal brain areas during feedback-based response learning. In a time estimation task, participants learned to press a button after…

  3. Neural Dynamics Underlying Event-Related Potentials

    NASA Technical Reports Server (NTRS)

    Shah, Ankoor S.; Bressler, Steven L.; Knuth, Kevin H.; Ding, Ming-Zhou; Mehta, Ashesh D.; Ulbert, Istvan; Schroeder, Charles E.

    2003-01-01

    There are two opposing hypotheses about the brain mechanisms underlying sensory event-related potentials (ERPs). One holds that sensory ERPs are generated by phase resetting of ongoing electroencephalographic (EEG) activity, and the other that they result from signal averaging of stimulus-evoked neural responses. We tested several contrasting predictions of these hypotheses by direct intracortical analysis of neural activity in monkeys. Our findings clearly demonstrate evoked response contributions to the sensory ERP in the monkey, and they suggest the likelihood that a mixed (Evoked/Phase Resetting) model may account for the generation of scalp ERPs in humans.

  4. Dynamics of quantum vorticity in a random potential.

    PubMed

    Link, Bennett

    2009-04-03

    I study the dynamics of a superfluid vortex in a random potential, as in the inner crust of a neutron star. Below a critical flow velocity of the ambient superfluid, a vortex is effectively immobilized by lattice forces even in the limit of zero dissipation. Low-velocity, translatory motion is not dynamically possible, a result with important implications for understanding neutron star precession and the dynamical properties of superfluid nuclear matter.

  5. Dynamic Assessment, Potential Giftedness and Mathematics Achievement in Elementary School

    ERIC Educational Resources Information Center

    Popa, Nicoleta Laura; Pauc, Ramona Loredana

    2015-01-01

    Dynamic assessment is currently discussed in educational literature as one of the most promising practices in stimulating learning among various groups of students, including gifted and potentially gifted students. The present study investigates effects of dynamic assessment on mathematics achievement among elementary school students, with…

  6. Hands typing what hands do: Action-semantic integration dynamics throughout written verb production.

    PubMed

    García, Adolfo M; Ibáñez, Agustín

    2016-04-01

    Processing action verbs, in general, and manual action verbs, in particular, involves activations in gross and hand-specific motor networks, respectively. While this is well established for receptive language processes, no study has explored action-semantic integration during written production. Moreover, little is known about how such crosstalk unfolds from motor planning to execution. Here we address both issues through our novel "action semantics in typing" paradigm, which allows to time keystroke operations during word typing. Specifically, we created a primed-verb-copying task involving manual action verbs, non-manual action verbs, and non-action verbs. Motor planning processes were indexed by first-letter lag (the lapse between target onset and first keystroke), whereas execution dynamics were assessed considering whole-word lag (the lapse between first and last keystroke). Each phase was differently delayed by action verbs. When these were processed for over one second, interference was strong and magnified by effector compatibility during programming, but weak and effector-blind during execution. Instead, when they were processed for less than 900ms, interference was reduced by effector compatibility during programming and it faded during execution. Finally, typing was facilitated by prime-target congruency, irrespective of the verbs' motor content. Thus, action-verb semantics seems to extend beyond its embodied foundations, involving conceptual dynamics not tapped by classical reaction-time measures. These findings are compatible with non-radical models of language embodiment and with predictions of event coding theory.

  7. A Neural Dynamic Model Generates Descriptions of Object-Oriented Actions.

    PubMed

    Richter, Mathis; Lins, Jonas; Schöner, Gregor

    2017-01-01

    Describing actions entails that relations between objects are discovered. A pervasively neural account of this process requires that fundamental problems are solved: the neural pointer problem, the binding problem, and the problem of generating discrete processing steps from time-continuous neural processes. We present a prototypical solution to these problems in a neural dynamic model that comprises dynamic neural fields holding representations close to sensorimotor surfaces as well as dynamic neural nodes holding discrete, language-like representations. Making the connection between these two types of representations enables the model to describe actions as well as to perceptually ground movement phrases-all based on real visual input. We demonstrate how the dynamic neural processes autonomously generate the processing steps required to describe or ground object-oriented actions. By solving the fundamental problems of neural pointing, binding, and emergent discrete processing, the model may be a first but critical step toward a systematic neural processing account of higher cognition.

  8. Photodynamic action of chlorin e6 on thymocyte plasmatic and mitochondrial membrane potentials

    NASA Astrophysics Data System (ADS)

    Gyulkhandanyan, Grigor V.

    2005-08-01

    Transmembrane potentials appear to be cell state sensitive characteristics and can give information about cell damage initial stage. Photodynamic action of the photosensitizer chlorin e6 on plasmatic and mitochondrial membrane potentials of the rat thymus lymphocytes was studied using voltage-sensitive dye rhodamine 6G. It has been revealed that mitochondrial membrane potential is more sensitive characteristic of membrane disfunction than plasmatic one at the cell photodamage.

  9. 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.

  10. DBI potential, DBI inflation action and general Lagrangian relative to phantom, K-essence and quintessence

    SciTech Connect

    Zhang, Qing; Huang, Yong-Chang

    2011-11-01

    We derive a Dirac-Born-Infeld (DBI) potential and DBI inflation action by rescaling the metric. The determinant of the induced metric naturally includes the kinetic energy and the potential energy. In particular, the potential energy and kinetic energy can convert into each other in any order, which is in agreement with the limit of classical physics. This is quite different from the usual DBI action. We show that the Taylor expansion of the DBI action can be reduced into the form in the non-linear classical physics. These investigations are the support for the statement that the results of string theory are consistent with quantum mechanics and classical physics. We deduce the Phantom, K-essence, Quintessence and Generalized Klein-Gordon Equation from the DBI model.

  11. Optical coherence tomography for detection of compound action potential in Xenopus Laevis sciatic nerve

    NASA Astrophysics Data System (ADS)

    Troiani, Francesca; Nikolic, Konstantin; Constandinou, Timothy G.

    2016-03-01

    Due to optical coherence tomography (OCT) high spatial and temporal resolution, this technique could be used to observe the quick changes in the refractive index that accompany action potential. In this study we explore the use of time domain Optical Coherence Tomography (TD-OCT) for real time action potential detection in ex vivo Xenopus Laevis sciatic nerve. TD-OCT is the easiest and less expensive OCT technique and, if successful in detecting real time action potential, it could be used for low cost monitoring devices. A theoretical investigation into the order of magnitude of the signals detected by a TD-OCT setup is provided by this work. A linear dependence between the refractive index and the intensity changes is observed and the minimum SNR for which the setup could work is found to be SNR = 2 x 104.

  12. 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.

  13. 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 %.

  14. Incorporated Fish Oil Fatty Acids Prevent Action Potential Shortening Induced by Circulating Fish Oil Fatty Acids

    PubMed Central

    Ruijter, Hester M. Den; Verkerk, Arie O.; Coronel, Ruben

    2010-01-01

    Increased consumption of fatty fish, rich in omega-3-polyunsaturated fatty acids (ω3-PUFAs) reduces the severity and number of arrhythmias. Long-term ω3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating ω3-PUFAs in the bloodstream and incorporated ω3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating ω3-PUFAs in the bloodstream enhance or diminish the effects of incorporated ω3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (ω3) or sunflower oil (ω9, as control) for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch-clamp technique in the absence and presence of acutely administered ω3-PUFAs. Plasma of ω3 fed rabbits contained more free eicosapentaenoic acid (EPA) and isolated myocytes of ω3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA) in their sarcolemma compared to control. In the absence of acutely administered fatty acids, ω3 myocytes had a shorter action potential with a more negative plateau than ω9 myocytes. In the ω9 myocytes, but not in the ω3 myocytes, acute administration of a mixture of EPA + DHA shortened the action potential significantly. From these data we conclude that incorporated ω3-PUFAs into the sarcolemma and acutely administered ω3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac ω3-PUFA status will probably not benefit from short term ω3 supplementation as an antiarrhythmic therapy. PMID:21423389

  15. Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus.

    PubMed

    Meeks, Julian P; Mennerick, Steven

    2004-01-07

    High-frequency synaptic transmission is depressed by moderate rises in the extracellular potassium concentration ([K+]o). Previous reports have indicated that depression of action potential signaling may underlie the synaptic depression. Here, we investigated the specific contribution of K+-induced action potential changes to synaptic depression. We found that glutamatergic transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that slows recovery from inactivation of voltage-gated sodium channels (NaChs), interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly. Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from inactivation. It is unclear from previous studies whether [K+]o-induced action potential depression is caused by changes in initiation, reliability, or waveform. We investigated these possibilities explicitly. [K+]o-induced afferent volley depression was independent of stimulus strength, suggesting that changes in action potential initiation do not explain [K+]o-induced depression. Measurements of action potentials from single axons revealed that 8 mM [K+]o increased conduction failures in a subpopulation of fibers and depressed action potential amplitude in all fibers. Together, these changes quantitatively account for the afferent volley depression. We estimate that conduction failure explains more than half of the synaptic depression observed at 8 mM [K+]o, with the remaining depression likely explained by waveform changes. These mechanisms of selective sensitivity of glutamate release to [K+]o accumulation represent a unique neuromodulatory mechanism and a brake on runaway excitation.

  16. Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

    PubMed

    Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

    2013-06-15

    Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations.

  17. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons.

    PubMed

    Raman, I M; Bean, B P

    1997-06-15

    Voltage-dependent sodium channels were studied in dissociated cerebellar Purkinje neurons from rats. In whole-cell recordings, a tetrodotoxin (TTX)-sensitive inward current was elicited when the membrane was repolarized to voltages between -60 and -20 mV after depolarizations to +30 mV long enough to produce maximal inactivation. At -40 mV, this "resurgent" current peaked in 8 msec and decayed with a time constant of 30 msec. With 50 mM sodium as a charge carrier, the resurgent current was on average approximately 120 pA. CA3 pyramidal neurons had no such current. The current may reflect recovery of inactivated channels through open states, because in Purkinje neurons (but not CA3 neurons) there was partial recovery from inactivation at -40 mV, coinciding with the rise of resurgent current. In single-channel recordings, individual channels gave openings corresponding to resurgent and conventional transient current. Action potentials were recorded from dissociated neurons under current clamp to investigate the role of the resurgent current in action potential formation. Purkinje neurons fired spontaneously at approximately 30 Hz. Hyperpolarization to -85 mV prevented spontaneous firing, and brief depolarization then induced all-or-none firing of conglomerate action potentials comprising three to four spikes. When conglomerate action potentials were used as command voltages in voltage-clamp experiments, TTX-sensitive sodium current was elicited between spikes. The falling phase of an action potential is similar to voltage patterns that activate resurgent sodium current, and thus, resurgent sodium current likely contributes to the formation of conglomerate action potentials in Purkinje neurons.

  18. Action principles for hydro- and thermo-dynamics

    NASA Astrophysics Data System (ADS)

    Fronsdal, Christian

    2017-03-01

    A Hamiltonian formulation of hydrodynamics is well known for the case of purely irrotational flows and it now exists in a more general case as well. The minimal extension of the action principle is obtained from two axioms: 1. That the number of independent degrees of freedom be 4, as in standard hydrodynamics. 2. That the equation of continuity must be one of the Euler-Lagrange equations, and that it allows for vorticity. Applications include: 1. Couette flow with a new criterion for the breakdown of laminar motion. 2. A rotating source for Einstein's equation that respects the Bianchi identity. 3. A new approach to the electromagnetism of fluids. 4. A rigorous virial theorem for fluids. 5. A critique of the current state of the theory of atmospheres.

  19. An integrated model for Jupiter's dynamo action and mean jet dynamics

    NASA Astrophysics Data System (ADS)

    Gastine, Thomas; Wicht, Johannes; Duarte, Lucia; Heimpel, Moritz

    2014-05-01

    Data from various space crafts revealed that Jupiter's large scale interior magnetic field is very Earth-like. This is surprising since numerical simulations have demonstrated that, for example, the radial dependence of density, electrical conductivity and other physical properties, which is only mild in the iron cores of terrestrial planets but very drastic in gas planets, can significantly affect the interior dynamics. Jupiter's dynamo action is thought to take place in the deeper envelope where hydrogen, the main constituent of Jupiter's atmosphere, assumes metallic properties. The potential interaction between the observed zonal jets and the deeper dynamo region is an unresolved problem with important consequences for the magnetic field generation. Here we present the first numerical simulation that is based on recent interior models and covers 99% of the planetary radius (below the 1 bar level). A steep decease in the electrical conductivity over the outer 10% in radius allowed us to model both the deeper metallic region and the outer molecular layer in an integrated approach. The magnetic field very closely reproduces Jupiter's known large scale field. A strong equatorial zonal jet remains constrained to the molecular layer while higher latitude jets are suppressed by Lorentz forces. This suggests that Jupiter's higher latitude jets remain shallow and are driven by an additional effect not captured in our deep convection model. The dynamo action of the equatorial jet produces a band of magnetic field located around the equator. The unprecedented magnetic field resolution expected from the Juno mission will allow to resolve this feature allowing a direct detection of the equatorial jet dynamics at depth. Typical secular variation times scales amount to around 750 yr for the dipole contribution but decrease to about 5 yr at the expected Juno resolution (spherical harmonic degree 20). At a nominal mission duration of one year Juno should therefore be able to

  20. 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.

  1. Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels.

    PubMed

    Jaffe, D B; Wang, B; Brenner, R

    2011-09-29

    The BK channel is a Ca(2+) and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca(2+) was high (>20 μM) and the other where BK-activating Ca(2+) was low (∼0.4-1.2 μM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca(2+) channels due to electrogenic effects on spike duration. We also found that depending on Ca(2+) dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron.

  2. The neuroendocrine action potential. Winner of the 2008 Frank Beach Award in Behavioral Neuroendocrinology.

    PubMed

    Hofmann, Hans A

    2010-09-01

    Animals are remarkably well equipped to respond to changes in their environment across different time scales and levels of biological organization. Here, I introduce a novel perspective that incorporates the three main processes the nervous system uses to integrate and process information: electrophysiological, genomic, and neuroendocrine action potentials. After discussing several examples of neuroendocrine action potentials, I lay out the commonalities of these temporally organized responses and how they might be interrelated with electrophysiological activity and genomic responses. This framework provides a novel outlook on longstanding questions in behavioral neuroendocrinology and suggests exciting new avenues for further research that will integrate across disciplines and levels of biological organization.

  3. Effects of some heavy metals on the action potentials of an identified Helix pomatia photosensitive neuron.

    PubMed

    Kartelija, Gordana; Radenović, Lidija; Todorović, Natasa; Nedeljković, Miodrag

    2005-06-01

    In the photosensitive MB neuron in the left parietal ganglion of Helix pomatia, the onset of light prolongs significantly (by about 40%) the duration of the action potential. The broadening of the action potential after the onset of light was found to be due to its calcium component and could not be induced after blocking Ca(2+) channels by Cd(2+) and Pb(2+) and in absence of Ca(2+) in medium. The blocking effect of both compounds was reversible. It was found that CdCl(2) exhibited a more intense blocking effect than PbCl(2).

  4. Catalysis of dynamical chiral symmetry breaking by chiral chemical potential

    NASA Astrophysics Data System (ADS)

    Braguta, V. V.; Kotov, A. Yu.

    2016-05-01

    In this paper, we study the properties of media with chiral imbalance parametrized by chiral chemical potential. It is shown that depending on the strength of interaction between constituents in the media the chiral chemical potential either creates or enhances dynamical chiral symmetry breaking. Thus, the chiral chemical potential plays the role of the catalyst of dynamical chiral symmetry breaking. Physically, this effect results from the appearance of the Fermi surface and additional fermion states on this surface, which take part in dynamical chiral symmetry breaking. An interesting conclusion which can be drawn is that at sufficiently small temperature chiral plasma is unstable with respect to condensation of Cooper pairs and dynamical chiral symmetry breaking even for vanishingly small interactions between constituents.

  5. Event-related potentials to intact and disrupted actions in children and adults

    PubMed Central

    Pace, Amy; Carver, Leslie J.; Friend, Margaret

    2013-01-01

    The current research used event-related potentials (ERPs) to investigate neurophysiological responses to intact and disrupted actions embedded within an event in children and adults. Responses were recorded as children (24-month-olds) and adults observed a relatively novel event composed of three actions. In one condition pauses were inserted at intact boundaries (i.e., at the endpoint of each action), whereas in the other condition they were inserted at breakpoints that disrupted the action (i.e., in the middle of each action). Evoked responses revealed differences across conditions in both groups; disrupted actions elicited a prolonged negative slow wave from 100 to 700 ms in children, whereas adults demonstrated two distinct negative peaks between 50–150 and 250–350 ms. These findings contribute the first electrophysiological evidence that children readily detect disruptions to ongoing events by the end of the second year, even with limited exposure to the event itself. Furthermore, they suggest that adults rely on two distinct mechanisms when processing novel events. Results are discussed in relation to the role of perceptual and conceptual levels of analysis in the development of action processing. PMID:23374603

  6. 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.

  7. Action potential propagation and propagation block by GABA in rat posterior pituitary nerve terminals.

    PubMed Central

    Jackson, M B; Zhang, S J

    1995-01-01

    1. A theoretical model was developed to investigate action potential propagation in posterior pituitary nerve terminals. This model was then used to evaluate the efficacy of depolarizing and shunting GABA responses on action potential propagation. 2. Experimental data obtained from the posterior pituitary with patch clamp techniques were used to derive empirical expressions for the voltage and time dependence of the nerve terminal Na+ and K+ channels. The essential structure employed here was based on anatomical and cable data from the posterior pituitary, and consisted of a long cylindrical axon (diameter, 0.5 mm) with a large spherical swelling (diameter, 4-21 mm) in the middle. 3. In the absence of an inhibitory conductance, simulated action potentials propagated with high fidelity through the nerve terminal. Swellings could block propagation, but only when sizes exceeded those observed in the posterior pituitary. Adding axonal branches reduced the critical size only slightly. These results suggested that action potentials invade the entire posterior pituitary nerve terminal in the absence of inhibition or depression. 4. The addition of inhibitory conductance to a swelling caused simulated action potentials to fail at the swelling. Depolarizing inhibitory conductances were 1.6 times more effective than shunting inhibitory conductances in blocking propagation. 5. Inhibitory conductances within the range of experimentally observed magnitudes and localized to swellings in the observed range of sizes were too weak to block simulated action potentials. However, twofold enhancement of GABA responses by neurosteroid resulted in currents strong enough to block propagation in realistic swelling sizes. 6. GABA could block simulated propagation without neurosteroid enhancement provided that GABA was present throughout a region in the order of a few hundred micrometres. For this widespread inhibition depolarizing conductance was 2.2 times more effective than shunting

  8. Dynamics of movement patterning in learning a discrete multiarticular action.

    PubMed

    Chow, Jia Yi; Davids, Keith; Button, Chris; Rein, Robert

    2008-07-01

    From a nonlinear dynamics perspective, presence of movement variability before a change in preferred movement patterns is hypothesized to afford the necessary adaptability and flexibility for seeking novel functional behaviors. In this study, four novice participants practiced a discrete multiarticular movement for 12 sessions over 4 weeks. Cluster analysis procedures revealed how changes between preferred movement patterns were affected with and without the presence of variability in movement clusters before a defined change. Performance improved in all participants as a function of practice. Participants typically showed evidence of change between preferred movement clusters and higher variability in the use of movement clusters within a session. However, increasing variability in movement clusters was not always accompanied by transition from one preferred movement cluster to another. In summary, it was observed that intentional and informational constraints play an important role in influencing the specific pathway of change for individual learners as they search for new preferred movement patterns.

  9. 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.

  10. Zinc-dependent action potentials in giant neurons of the snail, Euhadra quaestia.

    PubMed

    Kawa, K

    1979-09-14

    In giant neurons of subesophageal ganglion of the Japanese land snail, Euhadra quaestia Deshayes, permeation of Zn ions through Ca channels were investigated with a conventional current clamp method. All-or-none action potentials of long duration (90 to 120 sec) were evoked in 24 mM Zn containing salines. The overshoots were about +10 mV and the maximum rate of rises (MRRs) was about 2.9 V/sec. The amplitudes and the MRRs of the action potentials depended on external Zn ion concentrations. The action potentials were suppressed by specific Ca-channel inhibitors such as Co2+, La3+ and Verapamil, but they were resistant to Na-channel inhibitor, tetrodotoxin, even at 30 microM. It is concluded that these action potentials are generated by Zn ions permeating Ca channels in snail neuronal membrane. On the basis of Hagiwara and Takahashi's (S. Hagiwara & K. Takahashi, 1967, J. Gen. Physiol. 50:583) model of Ca channels, it is inferred that Zn ions are 5 to 10 times stronger in affinity to Ca channels than Ca ions, but 10 to 20 times less permeable.

  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. Ca2+ involvement in the action potential generation of myenteric neurones in the rat oesophagus.

    PubMed

    De Laet, A; Cornelissen, W; Adriaensen, D; Van Bogaert, P-P; Scheuermann, D W; Timmermans, J-P

    2002-04-01

    Intracellular recordings were used to study the physiological behaviour of rat oesophageal myenteric neurones, which are embedded in striated muscle. Injection of depolarizing pulses evoked action potentials with a clear 'shoulder' in all neurones. This shoulder disappeared under low Ca2+/high Mg2+ conditions. Tetrodotoxin (TTX; 1 micromol L-1) did not impede spike firing, whereas under combined TTX and low Ca2+/high Mg2+ conditions the action potentials were completely abolished, indicating that TTX- resistant action potentials are mediated by a Ca2+ current. Further experiments with omega-conotoxin GVIA (100 nmol L-1) revealed that these Ca2+ currents enter the cell via N-type voltage-activated Ca2+ channels (see also accompanying paper). Tetraethylammonium (10 mmol L-1) caused broadening of the action potentials, which probably resulted from prolonged Ca2+ influx due to blockade of the delayed rectifier K+ channel. Although Ca2+ appears to be involved in the spike generation of all rat oesophageal myenteric neurones, only a minority (14%) shows a slow afterhyperpolarization. Thus, no strict correlation exists between the presence of a shoulder and a slow afterhyperpolarization. Furthermore, morphological identification of 25 of the impaled neurones revealed that there was no strict correlation between morphology and electrophysiological behaviour. Consequently, rat oesophageal myenteric neurones appear to differ in several aspects from myenteric neurones in smooth muscle regions of the gastrointestinal tract.

  13. The Transformative Potential of Action Research and ICT in the Second Language (L2) Classroom

    ERIC Educational Resources Information Center

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

    2015-01-01

    This study shows the transformative potential of action research and information and communications technology (ICT) in the second language (L2) classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT…

  14. 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…

  15. Frontal oscillatory dynamics predict feedback learning and action adjustment.

    PubMed

    van de Vijver, Irene; Ridderinkhof, K Richard; Cohen, Michael X

    2011-12-01

    Frontal oscillatory dynamics in the theta (4-8 Hz) and beta (20-30 Hz) frequency bands have been implicated in cognitive control processes. Here we investigated the changes in coordinated activity within and between frontal brain areas during feedback-based response learning. In a time estimation task, participants learned to press a button after specific, randomly selected time intervals (300-2000 msec) using the feedback after each button press (correct, too fast, too slow). Consistent with previous findings, theta-band activity over medial frontal scalp sites (presumably reflecting medial frontal cortex activity) was stronger after negative feedback, whereas beta-band activity was stronger after positive feedback. Theta-band power predicted learning only after negative feedback, and beta-band power predicted learning after positive and negative feedback. Furthermore, negative feedback increased theta-band intersite phase synchrony (a millisecond resolution measure of functional connectivity) among right lateral prefrontal, medial frontal, and sensorimotor sites. These results demonstrate the importance of frontal theta- and beta-band oscillations and intersite communication in the realization of reinforcement learning.

  16. Ecstasy and methamphetamine elicit action potential bursts via different mechanisms in a central snail neuron.

    PubMed

    Lin, Pei-Lin; Tsai, Ming-Cheng; Lu, Guan-Ling; Lu, Dah-Yuu; Chuang, Chieh-Min; Yang, Han-Yin; Huang, Shiang-Suo; Chen, Yi-Hung

    2010-01-01

    This study sought to determine the effects of (+) methamphetamine (METH) and its ring-substituted analog (+/-)3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on electrophysiological behavior and their relationships to second messenger systems in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. Extracellular application of MDMA at 1mM and METH at 3mM elicited action potential bursts that were not blocked after immersing the neurons in Ca(2+)-free solution. Notably, MDMA- (1mM) elicited action potential bursts were blocked by pretreatment with the protein kinase C (PKC) inhibitors chelerythrine (20 microM) and Ro 31-8220 (20 microM), but not by the PKA inhibitors KT-5720 (10 microM) and H89 (10 microM). The PKC activator phorbol 12,13-dibutyrate (PDBu; 3 microM), but not the PKA activator forskolin (50 microM), facilitated the induction of bursts elicited by MDMA at a lower concentration (0.3mM). In contrast, METH- (3mM) elicited action potential bursts were blocked by pretreatment with KT-5720 (10 microM) and H89 (10 microM), but not by chelerythrine (20 microM) and Ro 31-8220 (20 microM). Forskolin (50 microM), but not PDBu (3 microM) facilitated the induction of bursts elicited by METH at a lower concentration (1mM). Tetraethylammonium chloride (TEA), a blocker of the delayed rectifying K(+) current (I(KD)), did not elicit bursts at a concentration of 5mM but did facilitate the induction of action potential bursts elicited by both METH and MDMA. Voltage clamp studies revealed that both METH and MDMA decreased the TEA-sensitive I(KD) of the RP4 neuron. Forskolin (50 microM) or dibutyryl cAMP (1mM), a membrane-permeable cAMP analog, alone did not elicit action potential bursts. However, co-administration with forskolin (50 microM) and TEA (5mM) or co-administration with dibutyryl cAMP (1mM) and TEA (50mM) elicited action potential bursts in the presence of the PKC inhibitor chelerythrine (20 microM). Similarly, PDBu (10 microM) or phorbol

  17. Beta-adrenergic stimulation reverses the IKr–IKs dominant pattern during cardiac action potential

    PubMed Central

    Banyasz, Tamas; Jian, Zhong; Horvath, Balazs; Khabbaz, Shaden; Izu, Leighton T.; Chen-Izu, Ye

    2014-01-01

    β-adrenergic stimulation differentially modulates different K+ channels and thus fine-tunes cardiac action potential (AP) repolarization. However, it remains unclear how the proportion of IKs, IKr, and IK1 current in the same cell would be altered by β-adrenergic stimulation, which would change the relative contribution of individual K+ current to the total repolarization reserve. In this study we used an innovative AP-clamp Sequential Dissection technique to directly record the dynamic –IKs, IKr, IK1– currents during the AP in guinea pig ventricular myocytes under physiologically relevant conditions. Our data provide quantitative measures of the magnitude and time course of IKs, IKr, IK1 currents in the same cell under its own steady-state AP, in a physiological milieu, and with preserved Ca2+ homeostasis. We found that isoproterenol treatment significantly enhanced IKs, moderately increased IK1, but slightly decreased IKr in a dose-dependent manner. The dominance pattern of the K+ currents was IKr>IK1>IKs at the control condition, but reversed to IKr

  18. The sequential encoding of competing action goals involves dynamic restructuring of motor plans in working memory.

    PubMed

    Gallivan, Jason P; Bowman, Natasha A R; Chapman, Craig S; Wolpert, Daniel M; Flanagan, J Randall

    2016-06-01

    Recent neural and behavioral findings provide support for the influential idea that in situations in which multiple action options are presented simultaneously, we prepare action plans for each competing option before deciding between and executing one of those plans. However, in natural, everyday environments, our available action options frequently change from one moment to the next, and there is often uncertainty as to whether additional options will become available before having to select a particular course of action. Here, with the use of a target-directed reaching task, we show that in this situation, the brain specifies a competing action for each new, sequentially presented potential target and that recently formed action plans can be revisited and updated so as to conform with separate, more newly developed, plans. These findings indicate that the brain forms labile motor plans for sequentially arising target options that can be flexibly restructured to accommodate new motor plans.

  19. Nucleation of carbon nanostructures: Molecular dynamics with reactive potentials

    NASA Astrophysics Data System (ADS)

    Galiullina, G. M.; Orekhov, N. D.; Stegailov, V. V.

    2016-11-01

    In this paper, we present our first results in the study of the details of nucleation in the homogeneous carbon gas phase using computer calculations with molecular dynamics methods. Direct and controlled molecular-dynamics approaches are used and two reactive potentials (ReaxFF and AIREBO) are compared. The calculations have shown that the nucleation process in the AIREBO model is going more actively than in the ReaxFF one.

  20. Sodium-calcium exchange during the action potential in guinea-pig ventricular cells.

    PubMed Central

    Egan, T M; Noble, D; Noble, S J; Powell, T; Spindler, A J; Twist, V W

    1989-01-01

    1. Slow inward tail currents attributable to electrogenic sodium-calcium exchange can be recorded by imposing hyperpolarizing voltage clamp pulses during the normal action potential of isolated guinea-pig ventricular cells. The hyperpolarizations return the membrane to the resting potential (between -65 and -88 m V) allowing an inward current to be recorded. This current usually has peak amplitude when repolarization is imposed during the first 50 ms after the action potential upstroke, but becomes negligible once the final phase of repolarization is reached. The envelope of peak current tail amplitudes strongly resembles that of the intracellular calcium transient recorded in other studies. 2. Repetitive stimulation producing normal action potentials at a frequency of 2 Hz progressively augments the tail current recorded immediately after the stimulus train. Conversely, if each action potential is prematurely terminated at 0.1 Hz, repetitive stimulation produces a tail current much smaller than the control value. The control amplitude of inward current is only maintained if interrupted action potentials are separated by at least one full 'repriming' action potential. These effects mimic those on cell contraction (Arlock & Wohlfart, 1986) and suggest that progressive changes in tail current are controlled by variations in the amplitude and time course of the intracellular calcium transient. 3. When intracellular calcium is buffered sufficiently to abolish contraction, the tail current is abolished. Substitution of calcium with strontium greatly reduces the tail current. 4. The inward tail current can also be recorded at more positive membrane potentials using standard voltage clamp pulse protocols. In this way it was found that temperature has a large effect on the tail current, which can change from net inward at 22 degrees C to net outward at 37 degrees C. The largest inward currents are usually recorded at about 30 degrees C. It is shown that this effect is

  1. 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.

  2. 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.

  3. Phorbol esters broaden the action potential in CA1 hippocampal pyramidal cells.

    PubMed

    Storm, J F

    1987-03-20

    Intracellular recordings were made from CA1 pyramidal cells in rat hippocampal slices. Single action potentials were elicited by injection of brief current pulses. Bath application of phorbol esters (4 beta-phorbol-12,13-diacetate, 0.3-5 microM; or 4 beta-phorbol-12,13-dibutyrate, 5-10 microM) broadened the action potential in each of the cells tested (n = 9). The broadening reflected slowing of the repolarization, whereas the upstroke of the spike was unchanged. This effect may enhance transmitter release from synaptic terminals, and contribute to enhancement of synaptic transmission through activation of protein kinase C, a mechanism which has been associated with long term potentiation.

  4. Potential dynamic impacts of wind turbines on utility systems

    NASA Astrophysics Data System (ADS)

    Zaininger, H. W.; Bell, D. J.

    1981-12-01

    This paper presents the results of an initial assessment of potential wind power generation dynamic impacts on utility systems from a global utility perspective performed for the Electric Power Research Institute. Dynamic study of minute-to-minute ramping, frequency excursions, and short-term transient stability was performed using the isolated Hawaiian Electric Company (HECO) system as an illustrative example. Potential minute-to-minute ramping requirements imposed on conventional generation units of two interconnected utilities, Kansas Gas and Electric (KG&E) and Public Service Company of Colorado (PSCo) were investigated, using interconnected utility operating criteria.

  5. Pseudospectral Gaussian quantum dynamics: Efficient sampling of potential energy surfaces.

    PubMed

    Heaps, Charles W; Mazziotti, David A

    2016-04-28

    Trajectory-based Gaussian basis sets have been tremendously successful in describing high-dimensional quantum molecular dynamics. In this paper, we introduce a pseudospectral Gaussian-based method that achieves accurate quantum dynamics using efficient, real-space sampling of the time-dependent basis set. As in other Gaussian basis methods, we begin with a basis set expansion using time-dependent Gaussian basis functions guided by classical mechanics. Unlike other Gaussian methods but characteristic of the pseudospectral and collocation methods, the basis set is tested with N Dirac delta functions, where N is the number of basis functions, rather than using the basis function as test functions. As a result, the integration for matrix elements is reduced to function evaluation. Pseudospectral Gaussian dynamics only requires O(N) potential energy calculations, in contrast to O(N(2)) evaluations in a variational calculation. The classical trajectories allow small basis sets to sample high-dimensional potentials. Applications are made to diatomic oscillations in a Morse potential and a generalized version of the Henon-Heiles potential in two, four, and six dimensions. Comparisons are drawn to full analytical evaluation of potential energy integrals (variational) and the bra-ket averaged Taylor (BAT) expansion, an O(N) approximation used in Gaussian-based dynamics. In all cases, the pseudospectral Gaussian method is competitive with full variational calculations that require a global, analytical, and integrable potential energy surface. Additionally, the BAT breaks down when quantum mechanical coherence is particularly strong (i.e., barrier reflection in the Morse oscillator). The ability to obtain variational accuracy using only the potential energy at discrete points makes the pseudospectral Gaussian method a promising avenue for on-the-fly dynamics, where electronic structure calculations become computationally significant.

  6. Affordance-based perception-action dynamics: A model of visually guided braking.

    PubMed

    Harrison, Henry S; Turvey, Michael T; Frank, Till D

    2016-04-01

    Behavioral dynamics is a framework for understanding adaptive behavior as arising from the self-organizing interaction between animal and environment. The methods of nonlinear dynamics provide a language for describing behavior that is both stable and flexible. Behavioral dynamics has been criticized for ignoring the animal's sensitivity to its own capabilities, leading to the development of an alternative framework: affordance-based control. Although it is theoretically sound and empirically motivated, affordance-based control has resisted characterization in terms of nonlinear dynamics. Here, we provide a dynamical description of affordance-based control, extending behavioral dynamics to meet its criticisms. We propose a general modeling strategy consistent with both theories. We use visually guided braking as a representative behavior and construct a novel dynamical model. This model demonstrates the possibility of understanding visually guided action as respecting the limits of the actor's capabilities, while still being guided by informational variables associated with desired states of affairs. In addition to such "hard" constraints on behavior, our framework allows for the influence of "soft" constraints such as preference and comfort, opening a new area of inquiry in perception-action dynamics.

  7. The effect of adrenaline on the temperature dependency of cardiac action potentials in pink salmon Oncorhynchus gorbuscha.

    PubMed

    Ballesta, S; Hanson, L M; Farrell, A P

    2012-04-01

    Using sharp electrode impalement, action potentials recorded from atrial and ventricular tissue of pink salmon Oncorhynchus gorbuscha generally decreased in duration with increasing test temperature (6, 10, 16 and 20° C). Stimulation of the tissue using 500 nM adrenaline had no significant effect on the duration of the atrial action potential at any test temperature but lengthened the ventricular action potential by ~17%.

  8. Variations in onset of action potential broadening: effects on calcium current studied in chick ciliary ganglion neurones.

    PubMed

    Pattillo, J M; Artim, D E; Simples, J E; Meriney, S D

    1999-02-01

    1. The voltage dependence and kinetic properties of stage 40 ciliary ganglion calcium currents were determined using short (10 ms) voltage steps. These properties aided the interpretation of the action potential-evoked calcium current described below, and the comparison of our data with those observed in other preparations. 2. Three different natural action potential waveforms were modelled by a series of ramps to generate voltage clamp commands. Calcium currents evoked by these model action potentials were compared before and after alterations in the repolarization phase of each action potential. 3. Abrupt step repolarizations from various time points were used to estimate the time course of calcium current activation during each action potential. Calcium current evoked by fast action potentials (duration at half-amplitude, 0.5 or 1.0 ms) did not reach maximal activation until the action potential had repolarized by 40-50 %. In contrast, calcium current evoked by a slow action potential (duration at half-amplitude, 2.2 ms) was maximally activated near the peak of the action potential. 4. Slowing the rate of repolarization of the action potential (broadening) from different times was used to examine effects on peak and total calcium influx. With all three waveforms tested, broadening consistently increased total calcium influx (integral). However, peak calcium current was either increased or decreased depending on the duration of the control action potential tested and the specific timing of the initiation of broadening the repolarization phase. 5. The opposite effects on peak calcium current observed with action potential broadening beginning at different time points in repolarization may provide a mechanism for the variable effects of potassium channel blockers on transmitter release magnitude.

  9. Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity.

    PubMed

    Chéreau, Ronan; Saraceno, G Ezequiel; Angibaud, Julie; Cattaert, Daniel; Nägerl, U Valentin

    2017-02-07

    Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.

  10. Education for Dynamic Economies: Action Plan To Accelerate Progress towards Education for All (EFA).

    ERIC Educational Resources Information Center

    World Bank, Washington, DC.

    The World Bank's development committee met and reviewed the paper, "Education for Dynamic Economies." The paper assessed progress and identified key issues and challenges in meeting the goals of universal primary education. It concluded that these goals were unlikely to be attained without accelerated action at the country level and a…

  11. The unifying role of dissipative action in the dynamic failure of solids

    DOE PAGES

    Grady, Dennis

    2015-05-19

    Dissipative action, the product of dissipation energy and transport time, is fundamental to the dynamic failure of solids. Invariance of the dissipative action underlies the fourth-power nature of structured shock waves observed in selected solid metals and compounds. Dynamic failure through shock compaction, tensile spall and adiabatic shear are also governed by a constancy of the dissipative action. This commonality underlying the various modes of dynamic failure is described and leads to deeper insights into failure of solids in the intense shock wave event. These insights are in turn leading to a better understanding of the shock deformation processes underlyingmore » the fourth-power law. Experimental result and material models encompassing the dynamic failure of solids are explored for the purpose of demonstrating commonalities leading to invariance of the dissipation action. As a result, calculations are extended to aluminum and uranium metals with the intent of predicting micro-scale energetics and spatial scales in the structured shock wave.« less

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

    PubMed

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

    2013-04-26

    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 IC50 values of 1.2 and 1.5mM, 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; IC50=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.

  13. Simple techniques suitable for student use to record action potentials from the frog heart.

    PubMed

    Yoshida, S

    2001-12-01

    Demonstrating action potentials during class experiments is very educational for science students. It is not easy, however, to obtain a stable intracellular recording of action potentials from the conventionally used skeletal muscle cells, because the tip of a glass microelectrode often comes out or breaks due to muscle contraction. Here, I present a much simpler recording method using a flexible polyethylene electrode with a wide orifice (approximately 1 mm) for a bullfrog heart beating on automaticity. Extracellular recordings of action potentials (electrocardiogram) can be obtained by placing an electrode on the cardiac surface, and transmembrane potentials can be obtained by rupturing the membrane with negative pressure, i.e., whole cell configuration. Once attached to the heart by suction, the polyethylene electrode does not easily come off during contraction of the heart. Perfusion of the heart via the postcaval vein offers us opportunities for observing the effects of either changing ionic compositions of solutions or applying drugs. The techniques shown here provide a simple and convenient way to perform a variety of class experiments.

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

    PubMed

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

    2012-03-09

    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.

  15. Evidence that the compound action potential (CAP) from the auditory nerve is a stationary potential generated across dura mater.

    PubMed

    Brown, Daniel J; Patuzzi, Robert B

    2010-08-01

    We have investigated the generation of the compound action potential (CAP) from the auditory nerve of guinea pigs. Responses to acoustic tone-bursts were recorded from the round window (RW), throughout the cochlear fluids, from the surface of the cochlear nucleus, from the central end of the auditory nerve after removal of the cochlear nucleus, from the scalp vertex, and from the contralateral ear. Responses were compared before, during and after experimental manipulations including pharmacological blockade of the auditory nerve, section of the auditory nerve, section of the efferent nerves, removal of the cochlear nucleus, and focal cooling of the cochlear nerve and/or cochlear nucleus. Regardless of the waveform changes occurring with these manipulations, the responses were similar in waveform but inverted polarity across the internal auditory meatus. The CAP waveforms were very similar before and after removal of the cochlear nucleus, apart from transient changes that could last many minutes. This suggests that the main CAP components are generated entirely by the eighth nerve. Based on previous studies and a clear understanding of the generation of extracellular potentials, we suggest that the early components in the responses recorded from the round window, from the cochlear fluids, from the surface of the cochlear nucleus, or from the scalp are a far-field or stationary potential, generated when the circulating action currents associated with each auditory neurone encounters a high extracellular resistance as it passes through the dura mater.

  16. Dynamic of cold-atom tips in anharmonic potentials.

    PubMed

    Menold, Tobias; Federsel, Peter; Rogulj, Carola; Hölscher, Hendrik; Fortágh, József; Günther, Andreas

    2016-01-01

    Background: Understanding the dynamics of ultracold quantum gases in an anharmonic potential is essential for applications in the new field of cold-atom scanning probe microscopy. Therein, cold atomic ensembles are used as sensitive probe tips to investigate nanostructured surfaces and surface-near potentials, which typically cause anharmonic tip motion. Results: Besides a theoretical description of this anharmonic tip motion, we introduce a novel method for detecting the cold-atom tip dynamics in situ and real time. In agreement with theory, the first measurements show that particle interactions and anharmonic motion have a significant impact on the tip dynamics. Conclusion: Our findings will be crucial for the realization of high-sensitivity force spectroscopy with cold-atom tips and could possibly allow for the development of advanced spectroscopic techniques such as Q-control.

  17. Dynamic of cold-atom tips in anharmonic potentials

    PubMed Central

    Menold, Tobias; Federsel, Peter; Rogulj, Carola; Hölscher, Hendrik; Fortágh, József

    2016-01-01

    Background: Understanding the dynamics of ultracold quantum gases in an anharmonic potential is essential for applications in the new field of cold-atom scanning probe microscopy. Therein, cold atomic ensembles are used as sensitive probe tips to investigate nanostructured surfaces and surface-near potentials, which typically cause anharmonic tip motion. Results: Besides a theoretical description of this anharmonic tip motion, we introduce a novel method for detecting the cold-atom tip dynamics in situ and real time. In agreement with theory, the first measurements show that particle interactions and anharmonic motion have a significant impact on the tip dynamics. Conclusion: Our findings will be crucial for the realization of high-sensitivity force spectroscopy with cold-atom tips and could possibly allow for the development of advanced spectroscopic techniques such as Q-control. PMID:28144505

  18. Muscle fibre conduction and fatigue during dynamic actions on a flywheel exercise device

    NASA Astrophysics Data System (ADS)

    Pozzo, Marco; Alkner, Bjorn; Norrbrand, Lena; Farina, Dario; Tesch, Per A.

    2005-08-01

    Exposure to microgravity has adverse effects on skeletal muscle size and function. Such effects can be counteracted by training using a Flywheel Exercise Device (FWED). Multichannel EMG signals were detected in nine males from vastus medialis and laterialis muscles during 30 coupled concentric (CON) and eccentric (ECC) actions on the FWED. Muscle fiber conduction velocity (CV) was assessed for each action. CV initial values depended on muscle action type (CON/ECC) and were higher in CON than ECC actions. CV decreased (P<0.05) over time during the task. Its slope was greater for VL than VM but was not different between CON and ECC. It was concluded that direct measure of CV is feasible during dynamic exercise, and that this technique may be used for objective assessment of the effect of resistance training in counteracting microgravity-induced muscle atrophy.

  19. Exploring action dynamics as an index of paired-associate learning.

    PubMed

    Dale, Rick; Roche, Jennifer; Snyder, Kristy; McCall, Ryan

    2008-03-05

    Much evidence exists supporting a richer interaction between cognition and action than commonly assumed. Such findings demonstrate that short-timescale processes, such as motor execution, may relate in systematic ways to longer-timescale cognitive processes, such as learning. We further substantiate one direction of this interaction: the flow of cognition into action systems. Two experiments explored match-to-sample paired-associate learning, in which participants learned randomized pairs of unfamiliar symbols. During the experiments, their hand movements were continuously tracked using the Nintendo Wiimote. Across learning, participant arm movements are initiated and completed more quickly, exhibit lower fluctuation, and exert more perturbation on the Wiimote during the button press. A second experiment demonstrated that action dynamics index novel learning scenarios, and not simply acclimatization to the Wiimote interface. Results support a graded and systematic covariation between cognition and action, and recommend ways in which this theoretical perspective may contribute to applied learning contexts.

  20. Potential applications of computational fluid dynamics to biofluid analysis

    NASA Technical Reports Server (NTRS)

    Kwak, D.; Chang, J. L. C.; Rogers, S. E.; Rosenfeld, M.; Kwak, D.

    1988-01-01

    Computational fluid dynamics was developed to the stage where it has become an indispensable part of aerospace research and design. In view of advances made in aerospace applications, the computational approach can be used for biofluid mechanics research. Several flow simulation methods developed for aerospace problems are briefly discussed for potential applications to biofluids, especially to blood flow analysis.

  1. Self-organized complementary joint action: Behavioral dynamics of an interpersonal collision-avoidance task.

    PubMed

    Richardson, Michael J; Harrison, Steven J; Kallen, Rachel W; Walton, Ashley; Eiler, Brian A; Saltzman, Elliot; Schmidt, R C

    2015-06-01

    Understanding stable patterns of interpersonal movement coordination is essential to understanding successful social interaction and activity (i.e., joint action). Previous research investigating such coordination has primarily focused on the synchronization of simple rhythmic movements (e.g., finger/forearm oscillations or pendulum swinging). Very few studies, however, have explored the stable patterns of coordination that emerge during task-directed complementary coordination tasks. Thus, the aim of the current study was to investigate and model the behavioral dynamics of a complementary collision-avoidance task. Participant pairs performed a repetitive targeting task in which they moved computer stimuli back and forth between sets of target locations without colliding into each other. The results revealed that pairs quickly converged onto a stable, asymmetric pattern of movement coordination that reflected differential control across participants, with 1 participant adopting a more straight-line movement trajectory between targets, and the other participant adopting a more elliptical trajectory between targets. This asymmetric movement pattern was also characterized by a phase lag between participants and was essential to task success. Coupling directionality analysis and dynamical modeling revealed that this dynamic regime was due to participant-specific differences in the coupling functions that defined the task-dynamics of participant pairs. Collectively, the current findings provide evidence that the dynamical coordination processes previously identified to underlie simple motor synchronization can also support more complex, goal-directed, joint action behavior, and can participate the spontaneous emergence of complementary joint action roles.

  2. Dynamical Green's function and an exact optical potential for electron-molecule scattering including nuclear dynamics

    NASA Astrophysics Data System (ADS)

    Brand, Joachim; Cederbaum, Lorenz S.; Meyer, Hans-Dieter

    1999-10-01

    We derive a rigorous optical potential for electron-molecule scattering including the effects of nuclear dynamics by extending the common many-body Green's function approach to optical potentials beyond the fixed-nuclei limit for molecular targets. Our formalism treats the projectile electron and the nuclear motion of the target molecule on the same footing whereby the dynamical optical potential rigorously accounts for the complex many-body nature of the scattering target. One central result of the present work is that the common fixed-nuclei optical potential is a valid adiabatic approximation to the dynamical optical potential even when projectile and nuclear motion are (nonadiabatically) coupled as long as the scattering energy is well below the electronic excitation thresholds of the target. For extremely low projectile velocities, however, when the cross sections are most sensitive to the scattering potential, we expect the influences of the nuclear dynamics on the optical potential to become relevant. For these cases, a systematic way to improve the adiabatic approximation to the dynamical optical potential is presented that yields nonlocal operators with respect to the nuclear coordinates.

  3. Modeling the attenuation and failure of action potentials in the dendrites of hippocampal neurons.

    PubMed Central

    Migliore, M

    1996-01-01

    We modeled two different mechanisms, a shunting conductance and a slow sodium inactivation, to test whether they could modulate the active propagation of a train of action potentials in a dendritic tree. Computer simulations, using a compartmental model of a pyramidal neuron, suggest that each of these two mechanisms could account for the activity-dependent attenuation and failure of the action potentials in the dendrites during the train. Each mechanism is shown to be in good qualitative agreement with experimental findings on somatic or dendritic stimulation and on the effects of hyperpolarization. The conditions under which branch point failures can be observed, and a few experimentally testable predictions, are presented and discussed. PMID:8913580

  4. Regulation of cough and action potentials by voltage-gated Na channels.

    PubMed

    Carr, Michael J

    2013-10-01

    The classical role ascribed to voltage-gated Na channels is the conduction of action potentials. Some excitable tissues such as cardiac muscle and skeletal muscle predominantly express a single voltage-gated Na channels isoform. Of the nine voltage-gated Na channels, seven are expressed in neurons, of these Nav 1.7, 1.8 and 1.9 are expressed in sensory neurons including vagal sensory neurons that innervate the airways and initiate cough. Nav 1.7 and Nav 1.9 are of particular interest as they represent two extremes in the functional diversity of voltage-gated Na channels. Voltage-gated Na channel isoforms expressed in airway sensory neurons produce multiple distinct Na currents that underlie distinct aspects of sensory neuron function. The interaction between voltage-gated Na currents underlies the characteristic ability of airway sensory nerves to encode encounters with irritant stimuli into action potential discharge and evoke the cough reflex.

  5. 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

  6. Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites.

    PubMed

    Bakkum, Douglas J; Frey, Urs; Radivojevic, Milos; Russell, Thomas L; Müller, Jan; Fiscella, Michele; Takahashi, Hirokazu; Hierlemann, Andreas

    2013-01-01

    Axons are traditionally considered stable transmission cables, but evidence of the regulation of action potential propagation demonstrates that axons may have more important roles. However, their small diameters render intracellular recordings challenging, and low-magnitude extracellular signals are difficult to detect and assign. Better experimental access to axonal function would help to advance this field. Here we report methods to electrically visualize action potential propagation and network topology in cortical neurons grown over custom arrays, which contain 11,011 microelectrodes and are fabricated using complementary metal oxide semiconductor technology. Any neuron lying on the array can be recorded at high spatio-temporal resolution, and simultaneously precisely stimulated with little artifact. We find substantial velocity differences occurring locally within single axons, suggesting that the temporal control of a neuron's output may contribute to neuronal information processing.

  7. Risperidone prolongs cardiac action potential through reduction of K+ currents in rabbit myocytes.

    PubMed

    Gluais, Pascale; Bastide, Michèle; Caron, Jacques; Adamantidis, Monique

    2002-05-31

    Prolongation of QT interval by antipsychotic drugs is an unwanted side effect that may lead to ventricular arrhythmias. The antipsychotic agent risperidone has been shown to cause QT prolongation, especially in case of overdosage. We investigated risperidone effects on action potentials recorded from rabbit Purkinje fibers and ventricular myocardium and on potassium currents recorded from atrial and ventricular rabbit isolated myocytes. The results showed that (1) risperidone (0.1-3 microM) exerted potent lengthening effects on action potential duration in both tissues with higher potency in Purkinje fibers and caused the development of early afterdepolarizations at low stimulation rate; (2) risperidone (0.03-0.3 microM) reduced significantly the current density of the delayed rectifier current and at 30 microM decreased the transient outward and the inward rectifier currents. This study might explain QT prolongation observed in some patients treated with risperidone and gives enlightenment on the risk of cardiac adverse events.

  8. A mathematical model of action potential in cells of vascular plants.

    PubMed

    Sukhov, Vladimir; Vodeneev, Vladimir

    2009-12-01

    A mathematical model of action potential (AP) in vascular plants cells has been worked out. The model takes into account actions of plasmalemma ion transport systems (K(+), Cl(-) and Ca(2+) channels; H(+)- and Ca(2+)-ATPases; 2H(+)/Cl(-) symporter; and H(+)/K(+) antiporter), changes of ion concentrations in the cell and in the extracellular space, cytoplasmic and apoplastic buffer capacities and the temperature dependence of active transport systems. The model of AP simulates a stationary level of the membrane potential and ion concentrations, generation of AP induced by electrical stimulation and gradual cooling and the impact of external Ca(2+) for AP development. The model supports a hypothesis about participation of H(+)-ATPase in AP generation.

  9. Monophasic action potentials in a patient with multiform ventricular tachycardia without QT prolongation.

    PubMed Central

    Emori, T; Ohe, T; Shimomura, K

    1993-01-01

    A 41 year old woman had multiform ventricular tachycardia without QT prolongation. Monophasic action potentials were recorded from the right ventricle during the attacks of multiform ventricular tachycardia and effective refractory periods were examined at the same sites. There was no abnormal hump to suggest early afterdepolarisation in the monophasic action potentials, but there was dispersion of the effective refractory period in the right ventricle (80 ms). Stimulation from the right ventricular apex, where the effective refractory period was shortest, reproducibly induced multiform ventricular tachycardia. Two weeks after admission, when her condition was stable, multiform ventricular tachycardia could not be induced and the dispersion of the effective refractory period in the right ventricle was 20 ms. PMID:8489870

  10. Antisense suppression of potassium channel expression demonstrates its role in maturation of the action potential.

    PubMed

    Vincent, A; Lautermilch, N J; Spitzer, N C

    2000-08-15

    A developmental increase in delayed rectifier potassium current (I(Kv)) in embryonic Xenopus spinal neurons is critical for the maturation of excitability and action potential waveform. Identifying potassium channel genes that generate I(Kv) is essential to understanding the mechanisms by which they are controlled. Several Kv genes are upregulated during embryogenesis in parallel with increases in I(Kv) and produce delayed rectifier current when heterologously expressed, indicating that they could encode channels underlying this current. We used antisense (AS) cRNA to test the contribution of xKv3.1 to the maturation of I(Kv), because xKv3.1 AS appears to suppress specifically heterologous expression of potassium current by xKv3.1 mRNA. The injection of xKv3.1 AS into embryos reduces endogenous levels of xKv3.1 mRNA in the developing spinal cord and reduces the amplitude and rate of activation of I(Kv) in 40% of cultured neurons, similar to the percentage of neurons in which endogenous xKv3.1 transcripts are detected. The current in these mature neurons resembles that at an earlier stage of differentiation before the appearance of xKv3.1 mRNA. Furthermore, AS expression increases the duration of the action potential in 40% of the neurons. No change in voltage-dependent calcium current is observed, suggesting that the decrease in I(Kv) is sufficient to account for lengthening of the action potential. Computer-simulated action potentials incorporating observed reductions in amplitude and rate of activation of I(Kv) exhibit an increase in duration similar to that observed experimentally. Thus xKv3.1 contributes to the maturation of I(Kv) in a substantial percentage of these developing spinal neurons.

  11. Autonomic control of cardiac action potentials: role of potassium channel kinetics in response to sympathetic stimulation.

    PubMed

    Terrenoire, Cecile; Clancy, Colleen E; Cormier, Joseph W; Sampson, Kevin J; Kass, Robert S

    2005-03-18

    I(Ks), the slowly activating component of the delayed rectifier current, plays a major role in repolarization of the cardiac action potential (AP). Genetic mutations in the alpha- (KCNQ1) and beta- (KCNE1) subunits of I(Ks) underlie Long QT Syndrome type 1 and 5 (LQT-1 and LQT-5), respectively, and predispose carriers to the development of polymorphic ventricular arrhythmias and sudden cardiac death. beta-adrenergic stimulation increases I(Ks) and results in rate dependent AP shortening, a control system that can be disrupted by some mutations linked to LQT-1 and LQT-5. The mechanisms by which I(Ks) regulates action potential duration (APD) during beta-adrenergic stimulation at different heart rates are not known, nor are the consequences of mutation induced disruption of this regulation. Here we develop a complementary experimental and theoretical approach to address these questions. We reconstituted I(Ks) in CHO cells (ie, KCNQ1 coexpressed with KCNE1 and the adaptator protein Yotiao) and quantitatively examined the effects of beta-adrenergic stimulation on channel kinetics. We then developed theoretical models of I(Ks) in the absence and presence of beta-adrenergic stimulation. We simulated the effects of sympathetic stimulation on channel activation (speeding) and deactivation (slowing) kinetics on the whole cell action potential under different pacing conditions. The model suggests these kinetic effects are critically important in rate-dependent control of action potential duration. We also investigate the effects of two LQT-5 mutations that alter kinetics and impair sympathetic stimulation of I(Ks) and show the likely mechanism by which they lead to tachyarrhythmias and indicate a distinct role of I(KS) kinetics in this electrical dysfunction. The full text of this article is available online at http://circres.ahajournals.org.

  12. Activity dependence of action potential duration in rat supraoptic neurosecretory neurones recorded in vitro.

    PubMed

    Bourque, C W; Renaud, L P

    1985-06-01

    Action potential durations, measured at one-third peak amplitude, were examined during intracellular recordings in 134 supraoptic nucleus neurones maintained in vitro in perfused hypothalamic explants. Spike durations ranged between 1.2 and 3.9 ms and were dependent on firing frequency. Shortest measurements (1.74 +/- 0.03 ms; mean +/- S.E. of mean) were obtained during relative quiescence, i.e. less than or equal to 0.5 Hz. A gradual increase in firing frequency through continuous injection of depolarizing current prolonged spike duration, with maximum levels (2.68 +/- 0.05 ms) achieved at 20 Hz. When interspike interval variability was eliminated and firing was more precisely regulated by brief 15-20 ms intracellular current pulses given at pre-determined frequencies, a proportional relationship between increasing spike duration and firing frequency was retained but the change in spike duration at frequencies between 2 and 10 Hz was less pronounced. Once action potentials had achieved the long duration configuration, their return to the shorter duration took place gradually during any succeeding silent interval with a time constant of 4.9 s. Action potential broadening occurred progressively and was most pronounced at the onset of spontaneous or current-induced bursts. In thirty-six phasically active neurones, spike broadening at the onset of a burst was concurrent with the presence of 5-10 consecutive short (less than or equal to 100 ms) interspike intervals; thereafter, despite a greater than 50% reduction in firing frequency, action potential durations remained prolonged throughout the burst. In all of nineteen cells tested, frequency-dependent changes in spike duration were reversibly decreased or blocked by Cd2+, Co2+ and Mn2+, or when CaCl2 was exchanged for equimolar amounts of EGTA in the perfusion medium. These observations indicate that a Ca2+ conductance contributes to frequency- and firing-pattern-dependent changes in spike duration in rat supraoptic

  13. Contributions of HERG K+ current to repolarization of the human ventricular action potential.

    PubMed

    Fink, Martin; Noble, Denis; Virag, Laszlo; Varro, Andras; Giles, Wayne R

    2008-01-01

    Action potential repolarization in the mammalian heart is governed by interactions of a number of time- and voltage-dependent channel-mediated currents, as well as contributions from the Na+/Ca2+ exchanger and the Na+/K+ pump. Recent work has shown that one of the K+ currents (HERG) which contributes to repolarization in mammalian ventricle is a locus at which a number of point mutations can have significant functional consequences. In addition, the remarkable sensitivity of this K+ channel isoform to inhibition by a variety of pharmacological agents and clinical drugs has resulted in HERG being a major focus for Safety Pharmacology requirements. For these reasons we and others have attempted to define the functional role for HERG-mediated K+ currents in repolarization of the action potential in the human ventricle. Here, we describe and evaluate changes in the formulations for two K+ currents, IK1 and HERG (or IK,r), within the framework of ten Tusscher model of the human ventricular action potential. In this computational study, new mathematical formulations for the two nonlinear K+ conductances, IK1 and HERG, have been developed based upon experimental data obtained from electrophysiological studies of excised human ventricular tissue and/or myocytes. The resulting mathematical model provides much improved simulations of the relative sizes and time courses of the K+ currents which modulate repolarization. Our new formulation represents an important first step in defining the mechanism(s) of repolarization of the membrane action potential in the human ventricle. Our overall goal is to understand the genesis of the T-wave of the human electrocardiogram.

  14. Effects of ropinirole on action potential characteristics and the underlying ion currents in canine ventricular myocytes.

    PubMed

    Simkó, József; Szentandrássy, Norbert; Harmati, Gábor; Bárándi, László; Horváth, Balázs; Magyar, János; Bányász, Tamás; Lorincz, István; Nánási, Péter P

    2010-09-01

    In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the dopamine receptor agonist ropinirole. In the present study, therefore, the concentration-dependent effects of ropinirole on action potential morphology and the underlying ion currents were studied in enzymatically dispersed canine ventricular cardiomyocytes using standard microelectrode, conventional whole-cell patch clamp, and action potential voltage clamp techniques. At concentrations > or = 1 microM, ropinirole increased action potential duration (APD(90)) and suppressed the rapid delayed rectifier K(+) current (I (Kr)) with an IC(50) value of 2.7 +/- 0.25 microM and Hill coefficient of 0.92 +/- 0.09. The block increased with increasing depolarizations to more positive voltages, but paradoxically, the activation of I (Kr) was accelerated by 3 muM ropinirole (time constant decreased from 34 +/- 4 to 14 +/- 1 ms). No significant changes in the fast and slow deactivation time constants were observed with ropinirole. At higher concentrations, ropinirole decreased the amplitude of early repolarization (at concentrations > or = 10 microM), reduced the maximum rate of depolarization and caused depression of the plateau (at concentrations > or = 30 microM), and shortened APD measured at 50% repolarization (at 300 microM) indicating a concentration-dependent inhibition of I (to), I (Na), and I (Ca). Suppression of I (Kr), I (to), and I (Ca) has been confirmed under conventional patch clamp and action potential voltage clamp conditions. I (Ks) and I (K1) were not influenced significantly by ropinirole at concentrations less than 300 microM. All these effects of ropinirole were fully reversible upon washout. The results indicate that ropinirole treatment may carry proarrhythmic risk for patients with inherited or acquired long QT syndrome due to inhibition of I (Kr)-especially in cases of accidental overdose or intoxication.

  15. Application of the optical method in experimental cardiology: action potential and intracellular calcium concentration measurement.

    PubMed

    Ronzhina, M; Cmiel, V; Janoušek, O; Kolářová, J; Nováková, M; Babula, P; Provazník, I

    2013-01-01

    It has been shown that, in addition to conventional contact electrode techniques, optical methods using fluorescent dyes can be successfully used for cardiac signal measurement. In this review, the physical and technical fundamentals of the method are described, as well as the properties of the most common systems for measuring action potentials and intracellular calcium concentration. Special attention is paid to summarizing limitations and trends in developing this method.

  16. Effective dynamics of cold atoms flowing in two ring-shaped optical potentials with tunable tunneling

    NASA Astrophysics Data System (ADS)

    Aghamalyan, Davit; Amico, Luigi; Kwek, L. C.

    2013-12-01

    We study the current dynamics of coupled atomic condensates flowing in two ring-shaped optical potentials. We provide a specific setup where the ring-ring coupling can be tuned in an experimentally feasible way. It is demonstrated that the imaginary time effective action of the system in a weak coupling regime provides a two-level-system dynamics for the phase slip across the two rings. Through two-mode Gross- Pitaevskii mean-field equations, the real-time dynamics of the population imbalance and the phase difference between the two condensates is thoroughly analyzed analytically, as a function of the relevant physical parameters of the system. In particular, we find that the macroscopic quantum self-trapping phenomenon is induced in the system if the flowing currents assume a nonvanishing difference.

  17. Dynamical nucleus-nucleus potential at short distances

    SciTech Connect

    Jiang Yongying; Wang Ning; Li Zhuxia; Scheid, Werner

    2010-04-15

    The dynamical nucleus-nucleus potentials for fusion reactions {sup 40}Ca+{sup 40}Ca, {sup 48}Ca+{sup 208}Pb, and {sup 126}Sn+{sup 130}Te are studied with the improved quantum molecular dynamics model together with the extended Thomas-Fermi approximation for the kinetic energies of nuclei. The obtained fusion barrier for {sup 40}Ca+{sup 40}Ca is in good agreement with the extracted fusion barrier from the measured fusion excitation function, and the depths of the fusion pockets are close to the results of time-dependent Hartree-Fock calculations. The energy dependence of the fusion barrier is also investigated. The fusion pocket becomes shallow for a heavy fusion system and almost disappears for heavy nearly symmetric systems, and the obtained potential at short distances is higher than the adiabatic potential.

  18. 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

  19. Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine.

    PubMed

    Targ, E F; Kocsis, J D

    1986-01-15

    The sciatic nerves of rats were demyelinated by microinjection of lysophosphatidylcholine. A variety of abnormalities such as conduction slowing and block were present. Application of the potassium channel blocker 4-aminopyridine (4-AP) to the lesion site, led to an increase in area of the compound action potential recorded across the site of demyelination. Single axon recordings revealed three types of changes that may account for the 4-AP-induced increase in the compound response. One group showed broadening of the action potential. Other axons showed hyperexcitability following 4-AP, as manifest by spontaneous firing and multiple spike discharge following a single stimulus. In some of the axons studied, 4-AP led to overcoming of conduction block. Although many axons showed increased excitability properties in the presence of 4-AP, the frequency-following ability of the axons was reduced, and the absolute refractory period of the axons was increased. These results indicate that pharmacological blockade of potassium channels with 4-AP not only leads to action potential broadening in demyelinated axons, but to a variety of excitability changes. These heterogeneous effects of 4-AP should be considered in the rationale for its clinical use.

  20. Concept of relative variability of cardiac action potential duration and its test under various experimental conditions.

    PubMed

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

    2016-01-01

    Beat-to-beat variability of action potential duration (short-term variability, SV) is an intrinsic property of mammalian myocardium. Since the majority of agents and interventions affecting SV may modify also action potential duration (APD), we propose here the concept of relative SV (RSV), where changes in SV are normalized to changes in APD and these data are compared to the control SV-APD relationship obtained by lengthening or shortening of action potentials by inward and outward current injections. Based on this concept the influence of the several experimental conditions like stimulation frequency, temperature, pH, redox-state and osmolarity were examined on RSV in canine ventricular myocytes using sharp microelectrodes. RSV was increased by high stimulation frequency (cycle lengths <0.7 s), high temperature (above 37ºC), oxidative agents (H2O2), while it was decreased by reductive environment. RSV was not affected by changes in pH (within the range of 6.4-8.4) and osmolarity of the solution (between 250-350 mOsm). The results indicate that changes in beat-to-beat variability of APD must be evaluated exclusively in terms of RSV; furthermore, some experimental conditions, including the stimulation frequency, redox-state and temperature have to be controlled strictly when analyzing alterations in the short-term variability of APD.

  1. TASK-1 Channels May Modulate Action Potential Duration of Human Atrial Cardiomyocytes

    PubMed Central

    Limberg, Sven H.; Netter, Michael F.; Rolfes, Caroline; Rinné, Susanne; Schlichthörl, Günter; Zuzarte, Marylou; Vassiliou, Timon; Moosdorf, Rainer; Wulf, Hinnerk; Daut, Jürgen; Sachse, Frank B.; Decher, Niels

    2011-01-01

    Background/Aims: Atrial fibrillation is the most common arrhythmia in the elderly, and potassium channels with atrium-specific expression have been discussed as targets to treat atrial fibrillation. Our aim was to characterize TASK-1 channels in human heart and to functionally describe the role of the atrial whole cell current ITASK-1. Methods and Results: Using quantitative PCR, we show that TASK-1 is predominantly expressed in the atria, auricles and atrio-ventricular node of the human heart. Single channel recordings show the functional expression of TASK-1 in right human auricles. In addition, we describe for the first time the whole cell current carried by TASK-1 channels (ITASK-1) in human atrial tissue. We show that ITASK-1 contributes to the sustained outward current IKsus and that ITASK-1 is a major component of the background conductance in human atrial cardiomyocytes. Using patch clamp recordings and mathematical modeling of action potentials, we demonstrate that modulation of ITASK-1 can alter human atrial action potential duration. Conclusion: Due to the lack of ventricular expression and the ability to alter human atrial action potential duration, TASK-1 might be a drug target for the treatment of atrial fibrillation. PMID:22178873

  2. Rate Dependence and Regulation of Action Potential and Calcium Transient in a Canine Cardiac Ventricular Cell Model

    PubMed Central

    Hund, Thomas J.; Rudy, Yoram

    2007-01-01

    Background Computational biology is a powerful tool for elucidating arrhythmogenic mechanisms at the cellular level, where complex interactions between ionic processes determine behavior. A novel theoretical model of the canine ventricular epicardial action potential and calcium cycling was developed and used to investigate ionic mechanisms underlying Ca2+ transient (CaT) and action potential duration (APD) rate dependence. Methods and Results The Ca2+/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was integrated into the model, which included a novel Ca2+-release formulation, Ca2+ subspace, dynamic chloride handling, and formulations for major ion currents based on canine ventricular data. Decreasing pacing cycle length from 8000 to 300 ms shortened APD primarily because of ICa(L) reduction, with additional contributions from Ito1, INaK, and late INa. CaT amplitude increased as cycle length decreased from 8000 to 500 ms. This positive rate–dependent property depended on CaMKII activity. Conclusions CaMKII is an important determinant of the rate dependence of CaT but not of APD, which depends on ion-channel kinetics. The model of CaMKII regulation may serve as a paradigm for modeling effects of other regulatory pathways on cell function. PMID:15505083

  3. Neural network potentials for dynamics and thermodynamics of gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Chiriki, Siva; Jindal, Shweta; Bulusu, Satya S.

    2017-02-01

    For understanding the dynamical and thermodynamical properties of metal nanoparticles, one has to go beyond static and structural predictions of a nanoparticle. Accurate description of dynamical properties may be computationally intensive depending on the size of nanoparticle. Herein, we demonstrate the use of atomistic neural network potentials, obtained by fitting quantum mechanical data, for extensive molecular dynamics simulations of gold nanoparticles. The fitted potential was tested by performing global optimizations of size selected gold nanoparticles (Aun, 17 ≤ n ≤ 58). We performed molecular dynamics simulations in canonical (NVT) and microcanonical (NVE) ensembles on Au17, Au34, Au58 for a total simulation time of around 3 ns for each nanoparticle. Our study based on both NVT and NVE ensembles indicate that there is a dynamical coexistence of solid-like and liquid-like phases near melting transition. We estimate the probability at finite temperatures for set of isomers lying below 0.5 eV from the global minimum structure. In the case of Au17 and Au58, the properties can be estimated using global minimum structure at room temperature, while for Au34, global minimum structure is not a dominant structure even at low temperatures.

  4. 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.

  5. T-type calcium channels consolidate tonic action potential output of thalamic neurons to neocortex.

    PubMed

    Deleuze, Charlotte; David, François; Béhuret, Sébastien; Sadoc, Gérard; Shin, Hee-Sup; Uebele, Victor N; Renger, John J; Lambert, Régis C; Leresche, Nathalie; Bal, Thierry

    2012-08-29

    The thalamic output during different behavioral states is strictly controlled by the firing modes of thalamocortical neurons. During sleep, their hyperpolarized membrane potential allows activation of the T-type calcium channels, promoting rhythmic high-frequency burst firing that reduces sensory information transfer. In contrast, in the waking state thalamic neurons mostly exhibit action potentials at low frequency (i.e., tonic firing), enabling the reliable transfer of incoming sensory inputs to cortex. Because of their nearly complete inactivation at the depolarized potentials that are experienced during the wake state, T-channels are not believed to modulate tonic action potential discharges. Here, we demonstrate using mice brain slices that activation of T-channels in thalamocortical neurons maintained in the depolarized/wake-like state is critical for the reliable expression of tonic firing, securing their excitability over changes in membrane potential that occur in the depolarized state. Our results establish a novel mechanism for the integration of sensory information by thalamocortical neurons and point to an unexpected role for T-channels in the early stage of information processing.

  6. Material Discovery and Design with Dynamic Charge Reactive Potentials

    NASA Astrophysics Data System (ADS)

    Sinnott, Susan

    2015-03-01

    Atomic scale computational simulations of multi-phase systems is increasingly important as our ability to simulate nanometer-sized systems becomes routine. The recently developed charge optimized many body potential (COMB) potentials have significantly enhanced our ability to carry out atomic-scale simulations of heterogeneous material systems. The formalism of this potential combines variable charge electrostatic interactions with a classical analytical bond-order potential. It therefore has the capacity to adaptively model metallic, covalent, ionic, and van der Waals bonding within the same simulation cell and dynamically determine the charges on individual atoms according to the local environment. The utility of the COMB potentials is illustrated for materials design and discovery by exploring the structure, stability, mechanical properties, and thermal properties of intermetallic systems and oxide-metal interfaces. They are also used to address key questions associated with corrosion, thin film growth, and heterogeneous catalysis.

  7. Barrel cortex membrane potential dynamics in social touch.

    PubMed

    Lenschow, Constanze; Brecht, Michael

    2015-02-18

    The impact of social stimuli on the membrane potential dynamics of barrel cortex neurons is unknown. We obtained in vivo whole-cell recordings in the barrel cortex of head-restrained rats while they interacted with conspecifics. Social touch was associated with a depolarization and large membrane potential fluctuations locked to the rat's whisking. Both depolarization and membrane potential fluctuations were already observed prior to contact and did not occur during free whisking. This anticipatory pre-contact depolarization was not seen in passive social touch in anesthetized animals. The membrane potential fluctuations locked to the rat's whisking observed in interactions with awake conspecifics were larger than those seen for whisking onto nonconspecific stimuli (stuffed rats, objects, and the experimenter's hand). Responses did not correlate with whisker movement parameters. We conclude that responses to social touch differ from conventional tactile responses in (1) amplitude, (2) locking to whisking, and (3) pre-contact membrane potential changes.

  8. Dynamical nonlocal coherent-potential approximation for itinerant electron magnetism.

    PubMed

    Rowlands, D A; Zhang, Yu-Zhong

    2014-11-26

    A dynamical generalisation of the nonlocal coherent-potential approximation is derived based upon the functional integral approach to the interacting electron problem. The free energy is proven to be variational with respect to the self-energy provided a self-consistency condition on a cluster of sites is satisfied. In the present work, calculations are performed within the static approximation and the effect of the nonlocal physics on the formation of the local moment state in a simple model is investigated. The results reveal the importance of the dynamical correlations.

  9. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

    PubMed

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

    2016-11-01

    Cardiac arrhythmias are associated with raised intracellular [Ca(2+)] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca(2+)-dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca(2+)-dependent phosphatase, calcineurin. Intracellular [Ca(2+)] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca(2)(+)]i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca(2+)]i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca(2+)-independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca(2+)]i. PP2A had no role. Conduction velocity was reduced by raised [Ca(2+)]i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca(2+)] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

  10. 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.

  11. Environmental Asthma Reduction Potential Estimates for Selected Mitigation Actions in Finland Using a Life Table Approach

    PubMed Central

    Rumrich, Isabell Katharina; Hänninen, Otto

    2015-01-01

    Aims: To quantify the reduction potential of asthma in Finland achievable by adjusting exposures to selected environmental factors. Methods: A life table model for the Finnish population for 1986–2040 was developed and Years Lived with Disability caused by asthma and attributable to the following selected exposures were estimated: tobacco smoke (smoking and second hand tobacco smoke), ambient fine particles, indoor dampness and mould, and pets. Results: At baseline (2011) about 25% of the total asthma burden was attributable to the selected exposures. Banning tobacco was the most efficient mitigation action, leading to 6% reduction of the asthma burden. A 50% reduction in exposure to dampness and mould as well as a doubling in exposure to pets lead each to a 2% reduction. Ban of urban small scale wood combustion, chosen as a mitigation action to reduce exposure to fine particles, leads to a reduction of less than 1% of the total asthma burden. Combination of the most efficient mitigation actions reduces the total asthma burden by 10%. A more feasible combination of mitigation actions leads to 6% reduction of the asthma burden. Conclusions: The adjustment of environmental exposures can reduce the asthma burden in Finland by up to 10%. PMID:26067987

  12. 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

  13. Traditional Chinese medicine: potential approaches from modern dynamical complexity theories.

    PubMed

    Ma, Yan; Zhou, Kehua; Fan, Jing; Sun, Shuchen

    2016-03-01

    Despite the widespread use of traditional Chinese medicine (TCM) in clinical settings, proving its effectiveness via scientific trials is still a challenge. TCM views the human body as a complex dynamical system, and focuses on the balance of the human body, both internally and with its external environment. Such fundamental concepts require investigations using system-level quantification approaches, which are beyond conventional reductionism. Only methods that quantify dynamical complexity can bring new insights into the evaluation of TCM. In a previous article, we briefly introduced the potential value of Multiscale Entropy (MSE) analysis in TCM. This article aims to explain the existing challenges in TCM quantification, to introduce the consistency of dynamical complexity theories and TCM theories, and to inspire future system-level research on health and disease.

  14. 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.

  15. A novel anionic conductance affects action potential duration in isolated rat ventricular myocytes.

    PubMed

    Spencer, C I; Uchida, W; Kozlowski, R Z

    2000-01-01

    Effects of extracellular anions were studied in electrophysiological experiments on freshly isolated rat ventricular myocytes. Under current-clamp, action potential duration (APD) was prolonged by reducing the extracellular Cl(-) concentration and shortened by replacement of extracellular Cl(-) with I(-). Under voltage-clamp, membrane potential steps or ramps evoked an anionic background current (I(AB)) carried by either Cl(-), Br(-), I(-) or NO(3)(-). Activation of I(AB) was Ca(2+)- and cyclic AMP-independent, and was unaffected by cell shrinkage. I(AB) was insensitive to stilbene and fenamate anion transport blockers at concentrations that inhibit Ca(2+)-, cyclic AMP- and swelling-activated Cl(-) currents in ventricular cells of other mammals. These results suggest that I(AB) may be carried by a novel class of Cl(-) channel. Correlation of anion substitution experiments on membrane current and action potentials revealed that I(AB) could play a major role in controlling rat ventricular APD. These findings have important implications for those studying cardiac Cl(-) channels as potential targets for novel antiarrythmic agents.

  16. Effects of rosiglitazone on the configuration of action potentials and ion currents in canine ventricular cells

    PubMed Central

    Szentandrássy, N; Harmati, G; Bárándi, L; Simkó, J; Horváth, B; Magyar, J; Bányász, T; Lőrincz, I; Szebeni, A; Kecskeméti, V; Nánási, PP

    2011-01-01

    BACKGROUND AND PURPOSE In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the antidiabetic drug rosiglitazone in larger experimental animals. In the present study therefore concentration-dependent effects of rosiglitazone on action potential morphology and the underlying ion currents were studied in dog hearts. EXPERIMENTAL APPROACH Standard microelectrode techniques, conventional whole cell patch clamp and action potential voltage clamp techniques were applied in enzymatically dispersed ventricular cells from dog hearts. KEY RESULTS At concentrations ≥10 µM rosiglitazone decreased the amplitude of phase-1 repolarization, reduced the maximum velocity of depolarization and caused depression of the plateau potential. These effects developed rapidly and were readily reversible upon washout. Rosiglitazone suppressed several transmembrane ion currents, concentration-dependently, under conventional voltage clamp conditions and altered their kinetic properties. The EC50 value for this inhibition was 25.2 ± 2.7 µM for the transient outward K+ current (Ito), 72.3 ± 9.3 µM for the rapid delayed rectifier K+ current (IKr) and 82.5 ± 9.4 µM for the L-type Ca2+ current (ICa) with Hill coefficients close to unity. The inward rectifier K+ current (IK1) was not affected by rosiglitazone up to concentrations of 100 µM. Suppression of Ito, IKr, and ICa was confirmed also under action potential voltage clamp conditions. CONCLUSIONS AND IMPLICATIONS Alterations in the densities and kinetic properties of ion currents may carry serious pro-arrhythmic risk in case of overdose with rosiglitazone, especially in patients having multiple cardiovascular risk factors, like elderly diabetic patients. LINKED ARTICLE This article is commented on by Hancox, pp. 496–498 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01281.x PMID:21232044

  17. FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels.

    PubMed

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S; Klyachko, Vitaly A

    2013-02-20

    Loss of FMRP causes fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx, and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely rescued in postnatal neurons. These presynaptic actions of FMRP are translation independent and are mediated selectively by BK channels via interaction of FMRP with BK channel's regulatory β4 subunits. Information-theoretical analysis demonstrates that loss of these FMRP functions causes marked dysregulation of synaptic information transmission. FMRP-dependent AP broadening is not limited to the hippocampus, but also occurs in cortical pyramidal neurons. Our results thus suggest major translation-independent presynaptic functions of FMRP that may have important implications for understanding FXS neuropathology.

  18. Quantum dynamics of relativistic bosons through nonminimal vector square potentials

    NASA Astrophysics Data System (ADS)

    de Oliveira, Luiz P.

    2016-09-01

    The dynamics of relativistic bosons (scalar and vectorial) through nonminimal vector square (well and barrier) potentials is studied in the Duffin-Kemmer-Petiau (DKP) formalism. We show that the problem can be mapped in effective Schrödinger equations for a component of the DKP spinor. An oscillatory transmission coefficient is found and there is total reflection. Additionally, the energy spectrum of bound states is obtained and reveals the Schiff-Snyder-Weinberg effect, for specific conditions the potential lodges bound states of particles and antiparticles.

  19. Image, word, action: interpersonal dynamics in a photo-sharing community.

    PubMed

    Suler, John

    2008-10-01

    In online photo-sharing communities, the individual's expression of self and the relationships that evolve among members is determined by the kinds of images that are shared, by the words exchanged among members, and by interpersonal actions that do not specifically rely on images or text. This article examines the dynamics of personal expression via images in Flickr, including a proposed system for identifying the dimensions of imagistic communication and a discussion of the psychological meanings embedded in a sequence of images. It explores how photographers use text descriptors to supplement their images and how different types of comments on photographs influence interpersonal relationships. The "fav"--when members choose an image as one of their favorites--is examined as one type of action that can serve a variety of interpersonal functions. Although images play a powerful role in the expression of self, it is the integration of images, words, and actions that maximize the development of relationships.

  20. Regional differences in action potential characteristics and membrane currents of guinea-pig left ventricular myocytes.

    PubMed

    Main, M C; Bryant, S M; Hart, G

    1998-11-01

    Regional differences in action potential characteristics and membrane currents were investigated in subendocardial, midmyocardial and subepicardial myocytes isolated from the left ventricular free wall of guinea-pig hearts. Action potential duration (APD) was dependent on the region of origin of the myocytes (P < 0.01, ANOVA). Mean action potential duration at 90 % repolarization (APD90) was 237 +/- 8 ms in subendocardial (n = 30 myocytes), 251 +/- 7 ms in midmyocardial (n = 30) and 204 +/- 7 ms in subepicardial myocytes (n = 36). L-type calcium current (ICa) density and background potassium current (IK1) density were similar in the three regions studied. Delayed rectifier current (IK) was measured as deactivating tail current, elicited on repolarization back to -45 mV after 2 s step depolarizations to test potentials ranging from -10 to +80 mV. Mean IK density (after a step to +80 mV) was larger in subepicardial myocytes (1.59 +/- 0.16 pA pF-1, n = 16) than in either subendocardial (1.16 +/- 0.12 pA pF-1, n = 17) or midmyocardial (1. 13 +/- 0.11 pA pF-1, n = 21) myocytes (P < 0.05, ANOVA). The La3+-insensitive current (IKs) elicited on repolarization back to -45 mV after a 250 ms step depolarization to +60 mV was similar in the three regions studied. The La3+-sensitive tail current, (IKr) was greater in subepicardial (0.50 +/- 0.04 pA pF-1, n = 11) than in subendocardial (0.25 +/- 0.05 pA pF-1, n = 9) or in midmyocardial myocytes (0.38 +/- 0.05 pA pF-1, n = 11, P < 0.05, ANOVA). The contribution of a Na+ background current to regional differences in APD was assessed by application of 0.1 microM tetrodotoxin (TTX). TTX-induced shortening of APD90 was greater in subendocardial myocytes (35.7 +/- 7.1 %, n = 11) than in midmyocardial (15.7 +/- 3. 8 %, n = 10) and subepicardial (20.2 +/- 4.3 %, n = 11) myocytes (P < 0.05, ANOVA). Regional differences in action potential characteristics between subendocardial, midmyocardial, and subepicardial myocytes isolated from

  1. Action-derived molecular dynamics in the study of rare events.

    PubMed

    Passerone, D; Parrinello, M

    2001-09-03

    We present a practical method to generate classical trajectories with fixed initial and final boundary conditions. Our method is based on the minimization of a suitably defined discretized action. The method finds its most natural application in the study of rare events. Its capabilities are illustrated by nontrivial examples. The algorithm lends itself to straightforward parallelization, and when combined with ab initio molecular dynamics it promises to offer a powerful tool for the study of chemical reactions.

  2. Dynamic Control of Neurotransmitter Release by Presynaptic Potential

    PubMed Central

    Zbili, Mickael; Rama, Sylvain; Debanne, Dominique

    2016-01-01

    Action potentials (APs) in the mammalian brain are thought to represent the smallest unit of information transmitted by neurons to their postsynaptic targets. According to this view, neuronal signaling is all-or-none or digital. Increasing evidence suggests, however, that subthreshold changes in presynaptic membrane potential before triggering the spike also determines spike-evoked release of neurotransmitter. We discuss here how analog changes in presynaptic voltage may regulate spike-evoked release of neurotransmitter through the modulation of biophysical state of voltage-gated potassium, calcium and sodium channels in the presynaptic compartment. The contribution of this regulation has been greatly underestimated and we discuss the impact for information processing in neuronal circuits. PMID:27994539

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

    PubMed Central

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

    2014-01-01

    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. PMID:24785307

  4. Stretch-induced excitation and action potential changes of single cardiac cells.

    PubMed

    Riemer, Tara L; Tung, Leslie

    2003-01-01

    Mechanoelectric coupling (MEC) has been studied extensively in the heart at the tissue and organ levels, but to only a limited extent in single cells because of the technical challenges. New results are presented in which MEC was studied in 57 single frog ventricular myocytes that were held on both ends by glass holding pipettes. Axial stretch was applied either by displacement of the pipettes, or by a glass fiber around which the cell was wrapped, that was displaced in a pulsatile or sinusoidal fashion. Electrical activity of the cell was monitored either by active contraction, by intracellular action potentials, or by focal extracellular potentials. Of more than 350 stretches applied to 57 cells with amplitudes ranging from 3% to 35%, only 4 cases of mechanically induced stimulation were observed. In 252 stretches applied to 32 cells in which action potential duration (APD) was measured, no change >20% was observed, except in 3 cells in which APD increased by >100%, and in 2 cells with extended triggered activity. Thus, in contrast to studies in intact tissue, single frog ventricular myocytes are generally insensitive to direct axial stretch. However, robust mechanosensitive responses were observed in 7 of 57 ( approximately 12%) cells. The results of other single cell studies are reviewed, and the significance of differences in tissue-level and single cell results is discussed.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. Neuronal Competition for Action Potential Initiation Sites in a Circuit Controlling Simple Learning

    PubMed Central

    Cruz, Georgina E.; Sahley, Christie L.; Muller, Kenneth J.

    2007-01-01

    The spatial and temporal patterns of action potential initiations were studied in a behaving leech preparation to determine the basis of increased firing that accompanies sensitization, a form of non-associative learning requiring the S-interneurons. Little is known at the network level about mechanisms of behavioral sensitization. The S-interneurons, one in each ganglion and linked by electrical synapses with both neighbors to form a chain, are interposed between sensory and motor neurons. In sensitized preparations the strength of shortening is related to S-cell firing, which itself is the result of impulses initiating in several S-cells. Because the S-cells, as independent initiation sites, all contribute to activity in the chain, it was hypothesized that during sensitization, increased multi-site activity increased the chain's firing rate. However, it was found that during sensitization, the single site with the largest initiation rate, the S-cell in the stimulated segment, suppressed initiations in adjacent ganglia. Experiments showed this was both because (1) it received the earliest, greatest input and (2) the delayed synaptic input to the adjacent S-cells coincided with the action potential refractory period. A compartmental model of the S-cell and its inputs showed that a simple, intrinsic mechanism of inexcitability after each action potential may account for suppression of impulse initiations. Thus, a non-synaptic competition between neurons alters synaptic integration in the chain. In one mode, inputs to different sites sum independently, whereas in another, synaptic input to a single site precisely specifies the overall pattern of activity. PMID:17644266

  10. Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation

    PubMed Central

    Collins, Anne L.; Greenfield, Venuz Y.; Bye, Jeffrey K.; Linker, Kay E.; Wang, Alice S.; Wassum, Kate M.

    2016-01-01

    Prolonged mesolimbic dopamine concentration changes have been detected during spatial navigation, but little is known about the conditions that engender this signaling profile or how it develops with learning. To address this, we monitored dopamine concentration changes in the nucleus accumbens core of rats throughout acquisition and performance of an instrumental action sequence task. Prolonged dopamine concentration changes were detected that ramped up as rats executed each action sequence and declined after earned reward collection. With learning, dopamine concentration began to rise increasingly earlier in the execution of the sequence and ultimately backpropagated away from stereotyped sequence actions, becoming only transiently elevated by the most distal and unexpected reward predictor. Action sequence-related dopamine signaling was reactivated in well-trained rats if they became disengaged in the task and in response to an unexpected change in the value, but not identity of the earned reward. Throughout training and test, dopamine signaling correlated with sequence performance. These results suggest that action sequences can engender a prolonged mode of dopamine signaling in the nucleus accumbens core and that such signaling relates to elements of the motivation underlying sequence execution and is dynamic with learning, overtraining and violations in reward expectation. PMID:26869075

  11. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation.

    PubMed

    Yue, L; Feng, J; Gaspo, R; Li, G R; Wang, Z; Nattel, S

    1997-10-01

    Rapid electrical activation, as occurs during atrial fibrillation (AF), is known to cause reductions in atrial refractoriness and in adaptation to heart rate of the atrial refractory period, which promote the maintenance of AF, but the underlying ionic mechanisms are unknown. In order to determine the cellular and ionic changes caused by chronic atrial tachycardia, we studied right atrial myocytes from dogs subjected to 1, 7, or 42 days of atrial pacing at 400/min and compared them with myocytes from sham-operated dogs (pacemaker inserted but not activated). Rapid pacing led to progressive increases in the duration of AF induced by bursts of 10-Hz stimuli (from 3 +/- 2 seconds in sham-operated dogs to 3060 +/- 707 seconds in dogs after 42 days of pacing, P < .001) and reduced atrial refractoriness and adaptation to rate of the atrial refractory period. Voltage-clamp studies showed that chronic rapid pacing did not alter inward rectifier K+ current, rapid or slow components of the delayed rectifier current, the ultrarapid delayed rectifier current, T-type Ca2+ current, or Ca(2+)-dependent Cl- current. In contrast, the densities of transient outward current (Ito) and L-type Ca2+ current (ICa) were progressively reduced as the duration of rapid pacing increased, without concomitant changes in kinetics or voltage dependence. In keeping with in vivo changes in refractoriness, action potential duration (APD) and APD adaptation to rate were decreased by rapid pacing. The response of the action potential and ionic currents flowing during the action potential (as exposed by action-potential voltage clamp) to nifedipine in normal canine cells and in cells from rapidly paced dogs suggested that the APD changes in paced dogs were largely due to reductions in ICa. We conclude that sustained atrial tachycardia reduces Ito and ICa, that the reduced ICa decreases APD and APD adaptation to rate, and that these cellular changes likely account for the alterations in atrial

  12. The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve.

    PubMed

    Li, Yongping; Lao, Jie; Zhao, Xin; Tian, Dong; Zhu, Yi; Wei, Xiaochun

    2014-01-15

    The distance between the two electrode tips can greatly influence the parameters used for recording compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spacings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance between two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential.

  13. The Healthy Bus project in Denmark: need for an action potential assessment.

    PubMed

    Poulsen, Kjeld B

    2004-06-01

    Research over the last 50 years has repeatedly documented that bus drivers are exposed to several physical and psychological risk factors, which are associated with health problems in the form of heart, musculo-skeletal and stomach disease, and increased coronary mortality. So why has there been little action to improve the situation when it is so obviously indicated by such assessments? This article describes the long and complex process that has made it possible to launch almost 200 interventions among the 3500 municipal bus drivers in Copenhagen. Using a participative action research design, new evidence was gathered by broadening the traditional work environmental scope to lifestyle, health issues and private matters. Comparing this updated needs assessment with a national reference population, it was found that drivers were often still worse off. Again, simply presenting new evidence did not seem to lead to changes and further work is needed to empower the stakeholders so that they can commit to start making effective interventions. It is concluded that every needs assessment has to be supplemented with an evaluation of the action potential.

  14. Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder.

    PubMed

    Takagi, Hiroaki; Hashitani, Hikaru

    2016-10-15

    The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization.

  15. Molecular dynamics simulations of solutions at constant chemical potential

    NASA Astrophysics Data System (ADS)

    Perego, C.; Salvalaglio, M.; Parrinello, M.

    2015-04-01

    Molecular dynamics studies of chemical processes in solution are of great value in a wide spectrum of applications, which range from nano-technology to pharmaceutical chemistry. However, these calculations are affected by severe finite-size effects, such as the solution being depleted as the chemical process proceeds, which influence the outcome of the simulations. To overcome these limitations, one must allow the system to exchange molecules with a macroscopic reservoir, thus sampling a grand-canonical ensemble. Despite the fact that different remedies have been proposed, this still represents a key challenge in molecular simulations. In the present work, we propose the Constant Chemical Potential Molecular Dynamics (CμMD) method, which introduces an external force that controls the environment of the chemical process of interest. This external force, drawing molecules from a finite reservoir, maintains the chemical potential constant in the region where the process takes place. We have applied the CμMD method to the paradigmatic case of urea crystallization in aqueous solution. As a result, we have been able to study crystal growth dynamics under constant supersaturation conditions and to extract growth rates and free-energy barriers.

  16. Effects of auroral potential drops on plasma sheet dynamics

    NASA Astrophysics Data System (ADS)

    Xi, Sheng; Lotko, William; Zhang, Binzheng; Wiltberger, Michael; Lyon, John

    2016-11-01

    The reaction of the magnetosphere-ionosphere system to dynamic auroral potential drops is investigated using the Lyon-Fedder-Mobarry global model including, for the first time in a global simulation, the dissipative load of field-aligned potential drops in the low-altitude boundary condition. This extra load reduces the field-aligned current (j||) supplied by nightside reconnection dynamos. The system adapts by forcing the nightside X line closer to Earth, with a corresponding reduction in current lensing (j||/B = constant) at the ionosphere and additional contraction of the plasma sheet during substorm recovery and steady magnetospheric convection. For steady and moderate solar wind driving and with constant ionospheric conductance, the cross polar cap potential and hemispheric field-aligned current are lower by approximately the ratio of the peak field-aligned potential drop to the cross polar cap potential (10-15%) when potential drops are included. Hemispheric ionospheric Joule dissipation is less by 8%, while the area-integrated, average work done on the fluid by the reconnecting magnetotail field increases by 50% within |y| < 8 RE. Effects on the nightside plasma sheet include (1) an average X line 4 RE closer to Earth; (2) a 12% higher mean reconnection rate; and (3) dawn-dusk asymmetry in reconnection with a 17% higher rate in the premidnight sector.

  17. Ridge-based bias potentials to accelerate molecular dynamics

    NASA Astrophysics Data System (ADS)

    Xiao, Penghao; Duncan, Juliana; Zhang, Liang; Henkelman, Graeme

    2015-12-01

    An effective way to accelerate rare events in molecular dynamics simulations is to apply a bias potential which destabilizes minima without biasing the transitions between stable states. This approach, called hyperdynamics, is limited by our ability to construct general bias potentials without having to understand the reaction mechanisms available to the system, a priori. Current bias potentials are typically constructed in terms of a metric which quantifies the distance that a trajectory deviates from the reactant state minimum. Such metrics include detection of negative curvatures of the potential, an energy increase, or deviations in bond lengths from the minimum. When one of these properties exceeds a critical value, the bias potentials are constructed to approach zero. A problem common to each of these schemes is that their effectiveness decreases rapidly with system size. We attribute this problem to a diminishing volume defined by the metrics around a reactant minimum as compared to the total volume of the reactant state basin. In this work, we mitigate the dimensionality scaling problem by constructing bias potentials that are based upon the distance to the boundary of the reactant basin. This distance is quantified in two ways: (i) by following the minimum mode direction to the reactant boundary and (ii) by training a machine learning algorithm to give an analytic expression for the boundary to which the distance can be calculated. Both of these ridge-based bias potentials are demonstrated to scale qualitatively better with dimensionality than the existing methods. We attribute this improvement to a greater filling fraction of the reactant state using the ridge-based bias potentials as compared to the standard potentials.

  18. Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe.

    PubMed

    Jin, Lei; Han, Zhou; Platisa, Jelena; Wooltorton, Julian R A; Cohen, Lawrence B; Pieribone, Vincent A

    2012-09-06

    Monitoring neuronal electrical activity using fluorescent protein-based voltage sensors has been limited by small response magnitudes and slow kinetics of existing probes. Here we report the development of a fluorescent protein voltage sensor, named ArcLight, and derivative probes that exhibit large changes in fluorescence intensity in response to voltage changes. ArcLight consists of the voltage-sensing domain of Ciona intestinalis voltage-sensitive phosphatase and super ecliptic pHluorin that carries the point mutation A227D. The fluorescence intensity of ArcLight A242 decreases by 35% in response to a 100 mV depolarization when measured in HEK293 cells, which is more than five times larger than the signals from previously reported fluorescent protein voltage sensors. We show that the combination of signal size and response speed of these new probes allows the reliable detection of single action potentials and excitatory potentials in individual neurons and dendrites.

  19. 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

    2016-08-11

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  1. Dynamics of Interacting Fermions in Spin-Dependent Potentials.

    PubMed

    Koller, Andrew P; Wall, Michael L; Mundinger, Josh; Rey, Ana Maria

    2016-11-04

    Recent experiments with dilute trapped Fermi gases observed that weak interactions can drastically modify spin transport dynamics and give rise to robust collective effects including global demagnetization, macroscopic spin waves, spin segregation, and spin self-rephasing. In this Letter, we develop a framework for studying the dynamics of weakly interacting fermionic gases following a spin-dependent change of the trapping potential which illuminates the interplay between spin, motion, Fermi statistics, and interactions. The key idea is the projection of the state of the system onto a set of lattice spin models defined on the single-particle mode space. Collective phenomena, including the global spreading of quantum correlations in real space, arise as a consequence of the long-ranged character of the spin model couplings. This approach achieves good agreement with prior measurements and suggests a number of directions for future experiments.

  2. Dynamics of Interacting Fermions in Spin-Dependent Potentials

    NASA Astrophysics Data System (ADS)

    Koller, Andrew P.; Wall, Michael L.; Mundinger, Josh; Rey, Ana Maria

    2016-11-01

    Recent experiments with dilute trapped Fermi gases observed that weak interactions can drastically modify spin transport dynamics and give rise to robust collective effects including global demagnetization, macroscopic spin waves, spin segregation, and spin self-rephasing. In this Letter, we develop a framework for studying the dynamics of weakly interacting fermionic gases following a spin-dependent change of the trapping potential which illuminates the interplay between spin, motion, Fermi statistics, and interactions. The key idea is the projection of the state of the system onto a set of lattice spin models defined on the single-particle mode space. Collective phenomena, including the global spreading of quantum correlations in real space, arise as a consequence of the long-ranged character of the spin model couplings. This approach achieves good agreement with prior measurements and suggests a number of directions for future experiments.

  3. Dynamical tides in general relativity: Effective action and effective-one-body Hamiltonian

    NASA Astrophysics Data System (ADS)

    Steinhoff, Jan; Hinderer, Tanja; Buonanno, Alessandra; Taracchini, Andrea

    2016-11-01

    Tidal effects have an important impact on the late inspiral of compact binary systems containing neutron stars. Most current models of tidal deformations of neutron stars assume that the tidal bulge is directly related to the tidal field generated by the companion, with a constant response coefficient. However, if the orbital motion approaches a resonance with one of the internal modes of the neutron star, this adiabatic description of tidal effects starts to break down, and the tides become dynamical. In this paper, we consider dynamical tides in general relativity due to the quadrupolar fundamental oscillation mode of a neutron star. We devise a description of the effects of the neutron star's finite size on the orbital dynamics based on an effective point-particle action augmented by dynamical quadrupolar degrees of freedom. We analyze the post-Newtonian and test-particle approximations of this model and incorporate the results into an effective-one-body Hamiltonian. This enables us to extend the description of dynamical tides over the entire inspiral. We demonstrate that dynamical tides give a significant enhancement of matter effects compared to adiabatic tides, at least for neutron stars with large radii and for low mass-ratio systems, and should therefore be included in accurate models for gravitational-wave data analysis.

  4. Epac activator critically regulates action potential duration by decreasing potassium current in rat adult ventricle.

    PubMed

    Brette, Fabien; Blandin, Erick; Simard, Christophe; Guinamard, Romain; Sallé, Laurent

    2013-04-01

    Sympathetic stimulation is an important modulator of cardiac function via the classic cAMP-dependent signaling pathway, PKA. Recently, this paradigm has been challenged by the discovery of a family of guanine nucleotide exchange proteins directly activated by cAMP (Epac), acting in parallel to the classic signaling pathway. In cardiac myocytes, Epac activation is known to modulate Ca(2+) cycling yet their actions on cardiac ionic currents remain poorly characterized. This study attempts to address this paucity of information using the patch clamp technique to record action potential (AP) and ionic currents on rat ventricular myocytes. Epac was selectively activated by 8-CPT-AM (acetoxymethyl ester form of 8-CPT). AP amplitude, maximum depolarization rate and resting membrane amplitude were unaltered by 8-CPT-AM, strongly suggesting that Na(+) current and inward rectifier K(+) current are not regulated by Epac. In contrast, AP duration was significantly increased by 8-CPT-AM (prolongation of duration at 50% and 90% of repolarization by 41±10% and 43±8% respectively, n=11). L-type Ca(2+) current density was unaltered by 8-CPT-AM (n=16) so this cannot explain the action potential lengthening. However, the steady state component of K(+) current was significantly inhibited by 8-CPT-AM (-38±6%, n=15), while the transient outward K(+) current was unaffected by 8-CPT-AM. These effects were PKA-independent since they were observed in the presence of PKA inhibitor KT5720. Isoprenaline (100nM) induced a significant prolongation of AP duration, even in the presence of KT5720. This study provides the first evidence that the cAMP-binding protein Epac critically modulates cardiac AP duration by decreasing steady state K(+) current. These observations may be relevant to diseases in which Epac is upregulated, like cardiac hypertrophy.

  5. The Influence of Glutamate on Axonal Compound Action Potential In Vitro

    PubMed Central

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs. PMID:28077958

  6. Targeting intracellular p-aminobenzoic acid production potentiates the anti-tubercular action of antifolates

    PubMed Central

    Thiede, Joshua M.; Kordus, Shannon L.; Turman, Breanna J.; Buonomo, Joseph A.; Aldrich, Courtney C.; Minato, Yusuke; Baughn, Anthony D.

    2016-01-01

    The ability to revitalize and re-purpose existing drugs offers a powerful approach for novel treatment options against Mycobacterium tuberculosis and other infectious agents. Antifolates are an underutilized drug class in tuberculosis (TB) therapy, capable of disrupting the biosynthesis of tetrahydrofolate, an essential cellular cofactor. Based on the observation that exogenously supplied p-aminobenzoic acid (PABA) can antagonize the action of antifolates that interact with dihydropteroate synthase (DHPS), such as sulfonamides and p-aminosalicylic acid (PAS), we hypothesized that bacterial PABA biosynthesis contributes to intrinsic antifolate resistance. Herein, we demonstrate that disruption of PABA biosynthesis potentiates the anti-tubercular action of DHPS inhibitors and PAS by up to 1000 fold. Disruption of PABA biosynthesis is also demonstrated to lead to loss of viability over time. Further, we demonstrate that this strategy restores the wild type level of PAS susceptibility in a previously characterized PAS resistant strain of M. tuberculosis. Finally, we demonstrate selective inhibition of PABA biosynthesis in M. tuberculosis using the small molecule MAC173979. This study reveals that the M. tuberculosis PABA biosynthetic pathway is responsible for intrinsic resistance to various antifolates and this pathway is a chemically vulnerable target whose disruption could potentiate the tuberculocidal activity of an underutilized class of antimicrobial agents. PMID:27905500

  7. 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

  8. 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

  9. Action-potential-independent GABAergic tone mediated by nicotinic stimulation of immature striatal miniature synaptic transmission.

    PubMed

    Liu, Zhi; Otsu, Yo; Vasuta, Cristina; Nawa, Hiroyuki; Murphy, Timothy H

    2007-08-01

    Stimulation of presynaptic nicotinic acetylcholine receptors (nAChRs) increases the frequency of miniature excitatory synaptic activity (mEPSCs) to a point where they can promote cell firing in hippocampal CA3 neurons. We have evaluated whether nicotine regulation of miniature synaptic activity can be extended to inhibitory transmission onto striatal medium spiny projection neurons (MSNs) in acute brain slices. Bath application of micromolar nicotine typically induced 12-fold increases in the frequency of miniature inhibitory synaptic currents (mIPSCs). Little effect was observed on the amplitude of mIPSCs or mEPSCs under these conditions. Nicotine stimulation of mIPSCs was dependent on entry of extracellular calcium because removal of calcium from perfusate was able to block its action. To assess the potential physiological significance of the nicotine-stimulated increase in mIPSC frequency, we also examined the nicotine effect on evoked IPSCs (eIPSCs). eIPSCs were markedly attenuated by nicotine. This effect could be attributed to two potential mechanisms: transmitter depletion due to extremely high mIPSC rates and/or a reduction in presynaptic excitability associated with nicotinic depolarization. Treatment with low concentrations of K(+) was able to in part mimic nicotine's stimulatory effect on mIPSCs and inhibitory effect on eIPSCs. Current-clamp recordings confirmed a direct depolarizing action of nicotine that could dampen eIPSC activity leading to a switch to striatal inhibitory synaptic transmission mediated by tonic mIPSCs.

  10. Amphetamine augments action potential-dependent dopaminergic signaling in the striatum in vivo.

    PubMed

    Ramsson, Eric S; Covey, Daniel P; Daberkow, David P; Litherland, Melissa T; Juliano, Steven A; Garris, Paul A

    2011-06-01

    Amphetamine (AMPH) is thought to disrupt normal patterns of action potential-dependent dopaminergic signaling by depleting dopamine (DA) vesicular stores and promoting non-exocytotic DA efflux. Voltammetry in brain slices concurrently demonstrates these key drug effects, along with competitive inhibition of neuronal DA uptake. Here, we perform comparable kinetic and voltammetric analyses in vivo to determine whether AMPH acts qualitatively and quantitatively similar in the intact brain. Fast-scan cyclic voltammetry measured extracellular DA in dorsal and ventral striata of urethane-anesthetized rats. Electrically evoked recordings were analyzed to determine K(m) and V(max) for DA uptake and vesicular DA release, while background voltammetric current indexed basal DA concentration. AMPH (0.5, 3, and 10 mg/kg i.p.) robustly increased evoked DA responses in both striatal subregions. The predominant contributor to these elevated levels was competitive uptake inhibition, as exocytotic release was unchanged in the ventral striatum and only modestly decreased in the dorsal striatum. Increases in basal DA levels were not detected. These results are consistent with AMPH augmenting action potential-dependent dopaminergic signaling in vivo across a wide, behaviorally relevant dose range. Future work should be directed at possible causes for the distinct in vitro and in vivo pharmacology of AMPH.

  11. Frequency-dependent inhibition of antidromic hippocampal compound action potentials by anti-convulsants.

    PubMed

    Teriakidis, Adrianna; Brown, Jon T; Randall, Andrew

    2006-01-01

    Using rat hippocampal slices, extracellularly recorded antidromic compound action potentials (cAP) were produced in CA1 pyramidal cell populations by electrical stimulation of the alveus at 0.5 Hz. These responses were additionally examined across a range of stimulus frequencies between 0.5 and 100 Hz. Anticonvulsant drugs in clinical use were applied via perfusion of the recording chamber. Three anticonvulsants produced a concentration-dependent inhibition of the cAP evoked at low frequency (0.5 Hz). The following IC(50) values were observed: lamotrigine, 210 microM (interpolated); carbamazepine, 210 microM (interpolated); phenytoin, 400 microM (extrapolated). The extent of inhibition produced was increased when trains of 30 cAPs were evoked at frequencies > or 30 Hz. This frequency dependence was quantified by measuring a response integral for a range of compound concentrations. Three other compounds valproate (5 mM), topiramate (500 microM) and levetiracetam (500 microM) produced no clear effect at any stimulus frequency tested. Using this simple neurophysiological assay it has been possible to compare the use-dependent inhibition of hippocampal action potentials by a range of anticonvulsants, providing a useful adjunct to patch clamp studies of such molecules at Na(+) channels. There is no clear correlation between the activity in this model and the clinical efficacy of these drugs in different forms of epilepsy.

  12. The use of sensory action potential to evaluate inferior alveolar nerve damage after orthognathic surgery.

    PubMed

    Calabria, Francesca; Sellek, Lucy; Gugole, Fabio; Trevisiol, Lorenzo; Trevisol, Lorenzo; Bertolasi, Laura; D'Agostino, Antonio

    2013-03-01

    To assess and monitor the common event of neurosensory disturbance to the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy, we used clinical sensory tests and neurophysiologic test sensory action potentials. The diagnostic value of these tests was evaluated by comparing them with the degree of nerve damage reported by patients. Fourteen patients undergoing bilateral sagittal split osteotomy were analyzed preoperatively and 2 years postoperatively. Patients were evaluated bilaterally for positive and negative symptoms: light touch sensation, paraesthesia, hyperesthesia, and dysaesthesia; a "sensation score" was then calculated for each patient. Patients were also asked if they would be willing to repeat the procedure knowing the sensation loss they had now. Next, the right and left IAN were evaluated using sensory action potential and correlated with the other results. Before surgery, the medium latency difference between left and right was lower compared with postsurgery, with all patients having some deficit. The reduction in medium amplitude of 67% after the intervention was statistically significant. The frequency of abnormal findings in the electrophysiologic tests indicating IAN injury correlated with subjective sensory alteration. All patients said that they would repeat the surgery. Electrophysiologic testing is recommended for the evaluation of nerve dysfunction and seems a sensitive method for accurately assessing postsurgical nerve conduction.

  13. Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains.

    PubMed

    Nourski, Kirill V; Abbas, Paul J; Miller, Charles A; Robinson, Barbara K; Jeng, Fuh-Cherng

    2005-04-01

    This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

  14. Modulation of action potential and calcium signaling by levetiracetam in rat sensory neurons.

    PubMed

    Ozcan, Mete; Ayar, Ahmet

    2012-06-01

    Levetiracetam (LEV), a new anticonvulsant agent primarily used to treat epilepsy, has been used in pain treatment but the cellular mechanism of this action remains unclear. This study aimed to investigate effects of LEV on the excitability and membrane depolarization-induced calcium signaling in isolated rat sensory neurons using the whole-cell patch clamp and fura 2-based ratiometric Ca(2+)-imaging techniques. Dorsal root ganglia (DRG) were excised from neonatal rats, and cultured following enzymatic and mechanical dissociation. Under current clamp conditions, acute application of LEV (30 µM, 100 µM and 300 µM) significantly increased input resistance and caused the membrane to hyperpolarize from resting membrane potential in a dose-dependent manner. Reversal potentials of action potential (AP) after hyperpolarising amplitudes were shifted to more negative, toward to potassium equilibrium potentials, after application of LEV. It also caused a decrease in number of APs in neurons fired multiple APs in response to prolonged depolarization. Fura-2 fluorescence Ca(2+) imaging protocols revealed that HiK(+) (30 mM)-induced intracellular free Ca(2+) ([Ca(2+)](i)) was inhibited to 97.8 ± 4.6% (n = 17), 92.6 ± 4.8% (n = 17, p < 0.01) and 89.1 ± 5.1% (n = 18, p < 0.01) after application of 30 µM, 100 µM and 300 µM LEV (respectively), without any significant effect on basal levels of [Ca(2+)](i). This is the first evidence for the effect of LEV on the excitability of rat sensory neurons through an effect which might involve activation of potassium channels and inhibition of entry of Ca(2+), providing new insights for cellular mechanism(s) of LEV in pain treatment modalities.

  15. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats.

    PubMed

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens J; Ney, Denise M

    2009-11-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral nutrition (PN)-induced mucosal hypoplasia. The objective was to determine what enteral protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 microg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1-3 and partial PN+GLP-2 plus EN for days 4-7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity and gain of body weight, and improved feed efficiency compared with PN+GLP-2 alone. EN induced greater ileal proglucagon expression, increased plasma concentration of bioactive GLP-2 by 35%, and reduced plasma dipeptidyl peptidase IV (DPP-IV) activity compared with PN+GLP-2 alone, P < 0.05. However, only whey protein, and not casein or soy, potentiated the ability of GLP-2 to reverse PN-induced mucosal hypoplasia and further increase ileal villus height, crypt depth, and mucosa cellularity compared with PN+GLP-2 alone, P < 0.05. The ability of whey protein to induce greater mucosal surface area was associated with decreased DPP-IV activity in ileum and colon compared with casein, soy, or PN+GLP-2 alone, P < 0.05. In conclusion, whey protein potentiates the action of GLP-2 to reverse PN-induced mucosal hypoplasia in association with decreased intestinal DPP-IV activity.

  16. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats

    PubMed Central

    Liu, Xiaowen; Murali, Sangita G.; Holst, Jens J.

    2009-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral nutrition (PN)-induced mucosal hypoplasia. The objective was to determine what enteral protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 μg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1–3 and partial PN+GLP-2 plus EN for days 4–7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity and gain of body weight, and improved feed efficiency compared with PN+GLP-2 alone. EN induced greater ileal proglucagon expression, increased plasma concentration of bioactive GLP-2 by 35%, and reduced plasma dipeptidyl peptidase IV (DPP-IV) activity compared with PN+GLP-2 alone, P < 0.05. However, only whey protein, and not casein or soy, potentiated the ability of GLP-2 to reverse PN-induced mucosal hypoplasia and further increase ileal villus height, crypt depth, and mucosa cellularity compared with PN+GLP-2 alone, P < 0.05. The ability of whey protein to induce greater mucosal surface area was associated with decreased DPP-IV activity in ileum and colon compared with casein, soy, or PN+GLP-2 alone, P < 0.05. In conclusion, whey protein potentiates the action of GLP-2 to reverse PN-induced mucosal hypoplasia in association with decreased intestinal DPP-IV activity. PMID:19776251

  17. Dynamic skeletal muscle stimulation and its potential in bone adaptation

    PubMed Central

    Qin, Y-X.; Lam, H.; Ferreri, S.; Rubin, C.

    2016-01-01

    To identify mechanotransductive signals for combating musculoskeletal deterioration, it is essential to determine the components and mechanisms critical to the anabolic processes of musculoskeletal tissues. It is hypothesized that the interaction between bone and muscle may depend on fluid exchange in these tissues by mechanical loading. It has been shown that intramedullary pressure (ImP) and low-level bone strain induced by muscle stimulation (MS) has the potential to mitigate bone loss induced by disuse osteopenia. Optimized MS signals, i.e., low-intensity and high frequency, may be critical in maintaining bone mass and mitigating muscle atrophy. The objectives for this review are to discuss the potential for MS to induce ImP and strains on bone, to regulate bone adaptation, and to identify optimized stimulation frequency in the loading regimen. The potential for MS to regulate blood and fluid flow will also be discussed. The results suggest that oscillatory MS regulates fluid dynamics with minimal mechanical strain in bone. The response was shown to be dependent on loading frequency, serving as a critical mediator in mitigating bone loss. A specific regimen of dynamic MS may be optimized in vivo to attenuate disuse osteopenia and serve as a biomechanical intervention in the clinical setting. PMID:20190376

  18. The Retarding Potential Analyzer for Dynamics Explorer-B

    NASA Technical Reports Server (NTRS)

    Hanson, W. B.; Heelis, R. A.; Power, R. A.; Lippincott, C. R.; Zuccaro, D. R.; Holt, B. J.; Harmon, L. H.; Sanatani, S.

    1981-01-01

    The Retarding Potential Analyzer for Dynamics Explorer B measures the bulk ion velocity in the direction of the spacecraft motion, the constituent ion concentrations and the ion temperature along the satellite path. These parameters are derived from a least squares fit to the ion number flux versus energy curve obtained by sweeping or stepping the voltage applied to the internal retarding grids of the RPA. In addition, the spectral characteristics of irregularities in the total ion concentration are determined by high time resolution measurements and by use of a comb filter. These data are obtained from a separate wide aperture-sensor.

  19. Back-propagating action potentials in pyramidal neurons: a putative signaling mechanism for the induction of Hebbian synaptic plasticity.

    PubMed

    Colbert, C M

    2001-01-01

    A hallmark of synaptic plasticity is the associative, or Hebbian, nature of its induction. By associative, we mean that the timing relationships between activity of the pre- and postsynaptic elements of a synapse determine whether synaptic strengths are modified. lt is well-established that associativity results, in large part, from the dual requirements for activation of the N-methyl-D-aspartate receptor-ionophore, namely presynaptic neurotransmitter release and postsynaptic depolarization. However, the specific dendritic events that provide the postsynaptic depolarization have been relatively unexplored. Increasing evidence suggests that back-propagating (i.e., antidromic) Na(+) action potentials provide the necessary postsynaptic depolarization to allow induction of associative synaptic plasticities. In hippocampal CAI and neocortical layer V pyramidal neurons, these action potentials provide much greater levels of dendritic depolarization than would be expected from synaptic currents alone. Moreover, they provide a relatively brief and synchronous depolarization throughout the dendritic arbor, allowing timing relationships to more directly reflect pre- and postsynaptic cell firing. Interestingly, certain properties of the back-propagating actions potentials differ from axonal or somatic action potentials in ways that seem to reflect their function. For example, the all-or-none property of action potential amplitude does not hold in the dendrites. In this review we discuss the back-propagating action potential as a dendritic signal that provides information to synapses about the firing state of the postsynaptic neuron. First, we consider the evidence that action potentials propagate back from the axon. Second, we describe the characteristics of the back-propagating action potential in terms of interactions of its underlying ionic currents. Third, we describe how these properties contribute to the timing aspects of the induction of long-term potentiation. Finally

  20. Action Potentials and Ion Conductances in Wild-type and CALHM1-knockout Type II Taste Cells.

    PubMed

    Ma, Zhongming; Saung, Wint Thu; Foskett, J Kevin

    2017-02-15

    Taste bud type II cells fire action potentials in response to tastants, triggering non-vesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. Here, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1-knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1-KO mice, and their associated non-selective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1-KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na(+) currents either estimated from action potentials or recorded from steady-state voltage-pulses, or action potential threshold, overshoot peak, after-hyperpolarization and firing frequency. However, Calhm1-deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials.

  1. Representation Learning of Temporal Dynamics for Skeleton-Based Action Recognition.

    PubMed

    Du, Yong; Fu, Yun; Wang, Liang

    2016-07-01

    Motion characteristics of human actions can be represented by the position variation of skeleton joints. Traditional approaches generally extract the spatial-temporal representation of the skeleton sequences with well-designed hand-crafted features. In this paper, in order to recognize actions according to the relative motion between the limbs and the trunk, we propose an end-to-end hierarchical RNN for skeleton-based action recognition. We divide human skeleton into five main parts in terms of the human physical structure, and then feed them to five independent subnets for local feature extraction. After the following hierarchical feature fusion and extraction from local to global, dimensions of the final temporal dynamics representations are reduced to the same number of action categories in the corresponding data set through a single-layer perceptron. In addition, the output of the perceptron is temporally accumulated as the input of a softmax layer for classification. Random scale and rotation transformations are employed to improve the robustness during training. We compare with five other deep RNN variants derived from our model in order to verify the effectiveness of the proposed network. In addition, we compare with several other methods on motion capture and Kinect data sets. Furthermore, we evaluate the robustness of our model trained with random scale and rotation transformations for a multiview problem. Experimental results demonstrate that our model achieves the state-of-the-art performance with high computational efficiency.

  2. Novel dynamic Bayesian networks for facial action element recognition and understanding

    NASA Astrophysics Data System (ADS)

    Zhao, Wei; Park, Jeong-Seon; Choi, Dong-You; Lee, Sang-Woong

    2011-12-01

    In daily life, language is an important tool of communication between people. Besides language, facial action can also provide a great amount of information. Therefore, facial action recognition has become a popular research topic in the field of human-computer interaction (HCI). However, facial action recognition is quite a challenging task due to its complexity. In a literal sense, there are thousands of facial muscular movements, many of which have very subtle differences. Moreover, muscular movements always occur simultaneously when the pose is changed. To address this problem, we first build a fully automatic facial points detection system based on a local Gabor filter bank and principal component analysis. Then, novel dynamic Bayesian networks are proposed to perform facial action recognition using the junction tree algorithm over a limited number of feature points. In order to evaluate the proposed method, we have used the Korean face database for model training. For testing, we used the CUbiC FacePix, facial expressions and emotion database, Japanese female facial expression database, and our own database. Our experimental results clearly demonstrate the feasibility of the proposed approach.

  3. Resistance to action potential depression of a rat axon terminal in vivo.

    PubMed

    Sierksma, Martijn C; Borst, J Gerard G

    2017-04-03

    The shape of the presynaptic action potential (AP) has a strong impact on neurotransmitter release. Because of the small size of most terminals in the central nervous system, little is known about the regulation of their AP shape during natural firing patterns in vivo. The calyx of Held is a giant axosomatic terminal in the auditory brainstem, whose biophysical properties have been well studied in slices. Here, we made whole-cell recordings from calyceal terminals in newborn rat pups. The calyx showed a characteristic burst firing pattern, which has previously been shown to originate from the cochlea. Surprisingly, even for frequencies over 200 Hz, the AP showed little or no depression. Current injections showed that the rate of rise of the AP depended strongly on its onset potential, and that the membrane potential after the AP (Vafter) was close to the value at which no depression would occur during high-frequency activity. Immunolabeling revealed that Nav1.6 is already present at the calyx shortly after its formation, which was in line with the fast recovery from AP depression that we observed in slice recordings. Our findings thus indicate that fast recovery from depression and an inter-AP membrane potential that minimizes changes on the next AP in vivo, together enable high timing precision of the calyx of Held already shortly after its formation.

  4. 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.

  5. Pattern-dependent Role of NMDA receptors in Action Potential Generation: Consequences on ERK Activation

    PubMed Central

    Zhao, Meilan; Adams, J. Paige

    2005-01-01

    Synaptic long-term potentiation is maintained through gene transcription, but how the nucleus is recruited remains controversial. Activation of extracellular-signal regulated kinases 1 and 2 (ERKs) with synaptic stimulation has been shown to require NMDA receptors (NMDARs), yet stimulation intensities sufficient to recruit action potentials (APs) also appear to be required. This has led us to ask the question whether NMDARs are necessary for AP generation as they relate to ERK activation. To test this, we examined the effects of NMDAR blockade on APs induced with synaptic stimulation using whole-cell current clamp recordings from CA1 pyramidal cells in hippocampal slices. NMDAR antagonists were found to potently inhibit APs generated with 5 and 100 Hz synaptic stimulation. Blockade of APs, and ERK activation, could be overcome with the addition of the GABA-A antagonist bicuculline, indicating that APs are sufficient to activate signals such as ERK in the nucleus and throughout the neuron in the continued presence of NMDAR antagonists. Interestingly, no effects of the NMDAR antagonists were observed when theta-burst stimulation (TBS) was used. This resistance to the antagonists is conferred by temporal summation during the bursts. These results clarify findings from a previous study showing that ERK activation induced with TBS is resistant to APV, in contrast to that induced with 5 Hz or 100 Hz stimulation, which is sensitive. By showing that NMDAR blockade inhibits AP generation, we demonstrate that a major role NMDARs play in cell-wide and nuclear ERK activation is through their contribution to action potential generation. PMID:16049179

  6. Calcium-dependent but action potential-independent BCM-like metaplasticity in the hippocampus.

    PubMed

    Hulme, Sarah R; Jones, Owen D; Ireland, David R; Abraham, Wickliffe C

    2012-05-16

    The Bienenstock, Cooper and Munro (BCM) computational model, which incorporates a metaplastic sliding threshold for LTP induction, accounts well for experience-dependent changes in synaptic plasticity in the visual cortex. BCM-like metaplasticity over a shorter timescale has also been observed in the hippocampus, thus providing a tractable experimental preparation for testing specific predictions of the model. Here, using extracellular and intracellular electrophysiological recordings from acute rat hippocampal slices, we tested the critical BCM predictions (1) that high levels of synaptic activation will induce a metaplastic state that spreads across dendritic compartments, and (2) that postsynaptic cell-firing is the critical trigger for inducing that state. In support of the first premise, high-frequency priming stimulation inhibited subsequent long-term potentiation and facilitated subsequent long-term depression at synapses quiescent during priming, including those located in a dendritic compartment different to that of the primed pathway. These effects were not dependent on changes in synaptic inhibition or NMDA/metabotropic glutamate receptor function. However, in contrast to the BCM prediction, somatic action potentials during priming were neither necessary nor sufficient to induce the metaplasticity effect. Instead, in broad agreement with derivatives of the BCM model, calcium as released from intracellular stores and triggered by M1 muscarinic acetylcholine receptor activation was critical for altering subsequent synaptic plasticity. These results indicate that synaptic plasticity in stratum radiatum of CA1 can be homeostatically regulated by the cell-wide history of synaptic activity through a calcium-dependent but action potential-independent mechanism.

  7. Mutual and asynchronous anticipation and action in sports as globally competitive and locally coordinative dynamics

    PubMed Central

    Fujii, Keisuke; Isaka, Tadao; Kouzaki, Motoki; Yamamoto, Yuji

    2015-01-01

    Humans interact by changing their actions, perceiving other’s actions and executing solutions in conflicting situations. Using oscillator models, nonlinear dynamics have been considered for describing these complex human movements as an emergence of self-organisation. However, these frameworks cannot explain the hierarchical structures of complex behaviours between conflicting inter-agent and adapting intra-agent systems, especially in sport competitions wherein mutually quick decision making and execution are required. Here we adopt a hybrid multiscale approach to model an attack-and-defend game during which both players predict the opponent’s movement and move with a delay. From both simulated and measured data, one synchronous outcome between two-agent (i.e. successful defence) can be described as one attractor. In contrast, the other coordination-breaking outcome (i.e. successful attack) cannot be explained using gradient dynamics because the asymmetric interaction cannot always assume a conserved physical quantity. Instead, we provide the asymmetric and asynchronous hierarchical dynamical models to discuss two-agent competition. Our framework suggests that possessing information about an opponent and oneself in local-coordinative and global-competitive scale enables us to gain a deeper understanding of sports competitions. We anticipate developments in the scientific fields of complex movement adapting to such uncontrolled environments. PMID:26538452

  8. Mutual and asynchronous anticipation and action in sports as globally competitive and locally coordinative dynamics

    NASA Astrophysics Data System (ADS)

    Fujii, Keisuke; Isaka, Tadao; Kouzaki, Motoki; Yamamoto, Yuji

    2015-11-01

    Humans interact by changing their actions, perceiving other’s actions and executing solutions in conflicting situations. Using oscillator models, nonlinear dynamics have been considered for describing these complex human movements as an emergence of self-organisation. However, these frameworks cannot explain the hierarchical structures of complex behaviours between conflicting inter-agent and adapting intra-agent systems, especially in sport competitions wherein mutually quick decision making and execution are required. Here we adopt a hybrid multiscale approach to model an attack-and-defend game during which both players predict the opponent’s movement and move with a delay. From both simulated and measured data, one synchronous outcome between two-agent (i.e. successful defence) can be described as one attractor. In contrast, the other coordination-breaking outcome (i.e. successful attack) cannot be explained using gradient dynamics because the asymmetric interaction cannot always assume a conserved physical quantity. Instead, we provide the asymmetric and asynchronous hierarchical dynamical models to discuss two-agent competition. Our framework suggests that possessing information about an opponent and oneself in local-coordinative and global-competitive scale enables us to gain a deeper understanding of sports competitions. We anticipate developments in the scientific fields of complex movement adapting to such uncontrolled environments.

  9. Toxin detection based on action potential shape analysis using a realistic mathematical model of differentiated NG108-15 cells

    PubMed Central

    Mohan, Dinesh K; Molnar, Peter; Hickman, James J.

    2010-01-01

    The NG108-15 neuroblastoma / glioma hybrid cell line has been frequently used for toxin detection, pharmaceutical screening and as a whole-cell biosensor. However, detailed analysis of its action potentials during toxin or drug administration has not been accomplished previously using patch clamp electrophysiology. In order to explore the possibility of identifying toxins based on their effect on the shape of intracellularly or extracellularly detected action potentials, we created a computer model of the action potential generation of this cell type. To generate the experimental data to validate the model, voltage dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated in the model and were optimized to represent the actual recorded action potentials to establish baseline conditions. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently and their respective effects were identified based on the changes in the fitted parameters. Our results represent one of the first steps to establish a complex model of NG108-15 cells for quantitative toxin detection based on action potential shape analysis of the experimental results. PMID:16460924

  10. Action potential initiation in the peripheral terminals of cold-sensitive neurones innervating the guinea-pig cornea.

    PubMed

    Carr, Richard W; Pianova, Svetlana; McKemy, David D; Brock, James A

    2009-03-15

    The site at which action potentials initiate within the terminal region of unmyelinated sensory axons has not been resolved. Combining recordings of nerve terminal impulses (NTIs) and collision analysis, the site of action potential initiation in guinea-pig corneal cold receptors was determined. For most receptors (77%), initiation mapped to a point in the time domain that was closer to the nerve terminal than to the site of electrical stimulation at the back of the eye. Guinea-pig corneal cold receptors are Adelta-neurones that lose their myelin sheath at the point where they enter the cornea, and therefore their axons conduct more slowly within the cornea. Allowing for this inhomogeneity in conduction speed, the resulting spatial estimates of action potential initiation sites correlated with changes in NTI shape predicted by simulation of action potentials initiating within a nerve terminal. In some receptors, more than one NTI shape was observed. Simulations of NTI shape suggest that the origin of differing NTI shapes result from action potentials initiating at different, spatially discrete, locations within the nerve terminal. Importantly, the relative incidence of NTI shapes resulting from action potential initiation close to the nerve termination increased during warming when nerve activity decreased, indicating that the favoured site of action potential initiation shifts toward the nerve terminal when it hyperpolarizes. This finding can be explained by a hyperpolarization-induced relief of Na(+) channel inactivation in the nerve terminal. The results provide direct evidence that the molecular entities responsible for stimulus transduction and action potential initiation reside in parallel with one another in the unmyelinated nerve terminals of cold receptors.

  11. Unifying role of dissipative action in the dynamic failure of solids

    SciTech Connect

    Grady, Dennis E.

    2015-04-28

    A fourth-power law underlying the steady shock-wave structure and solid viscosity of condensed material has been observed for a wide range of metals and non-metals. The fourth-power law relates the steady-wave Hugoniot pressure to the fourth power of the strain rate during passage of the material through the structured shock wave. Preceding the fourth-power law was the observation in a shock transition that the product of the shock dissipation energy and the shock transition time is a constant independent of the shock pressure amplitude. Invariance of this energy-time product implies the fourth-power law. This property of the shock transition in solids was initially identified as a shock invariant. More recently, it has been referred to as the dissipative action, although no relationship to the accepted definitions of action in mechanics has been demonstrated. This same invariant property has application to a wider range of transient failure phenomena in solids. Invariance of this dissipation action has application to spall fracture, failure through adiabatic shear, shock compaction of granular media, and perhaps others. Through models of the failure processes, a clearer picture of the physics underlying the observed invariance is emerging. These insights in turn are leading to a better understanding of the shock deformation processes underlying the fourth-power law. Experimental result and material models encompassing the dynamic failure of solids are explored for the purpose of demonstrating commonalities leading to invariance of the dissipation action. Calculations are extended to aluminum and uranium metals with the intent of predicting micro-scale dynamics and spatial structure in the steady shock wave.

  12. Neural mechanisms underlying immediate and final action goals in object use reflected by slow wave brain potentials.

    PubMed

    van Schie, Hein T; Bekkering, Harold

    2007-05-07

    Event-related brain potentials were used to study the neural mechanisms underlying goal-directed object use distinguishing between processes supporting immediate and final action goals during action planning and execution. Subjects performed a grasping and transportation task in which actions were cued either with the immediate action goal (the part of the object to grasp) or with the final action goal of the movement (the end position for transportation). Slow wave potentials dissociated between processes supporting immediate and final goals: reaching for the object was accompanied by the development of a parietal-occipital slow wave that peaked in congruency with the grasping event, whereas transport of the object towards the final goal location was found accompanied by slow wave components developing over left frontal regions with a peak towards the movement end. Source localization of cueing differences indicated activation centered around the parieto-occipital sulcus during reaching of the immediate action goal, followed by enhanced activation in the anterior prefrontal cortex during transport to the final action goal. These results suggest the existence of separate neural controllers for immediate and final action goals during the execution of goal-directed actions with objects.

  13. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons

    PubMed Central

    Tan, Y P; Llano, I

    1999-01-01

    Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. α-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; α-dendrotoxin had no effect. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, α-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. α-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening. PMID:10517801

  14. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons.

    PubMed

    Tan, Y P; Llano, I

    1999-10-01

    1. Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. 2. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. alpha-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. 3. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; alpha-dendrotoxin had no effect. 4. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, alpha-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. alpha-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening.

  15. Action versus Result-Oriented Schemes in a Grassland Agroecosystem: A Dynamic Modelling Approach

    PubMed Central

    Sabatier, Rodolphe; Doyen, Luc; Tichit, Muriel

    2012-01-01

    Effects of agri-environment schemes (AES) on biodiversity remain controversial. While most AES are action-oriented, result-oriented and habitat-oriented schemes have recently been proposed as a solution to improve AES efficiency. The objective of this study was to compare action-oriented, habitat-oriented and result-oriented schemes in terms of ecological and productive performance as well as in terms of management flexibility. We developed a dynamic modelling approach based on the viable control framework to carry out a long term assessment of the three schemes in a grassland agroecosystem. The model explicitly links grazed grassland dynamics to bird population dynamics. It is applied to lapwing conservation in wet grasslands in France. We ran the model to assess the three AES scenarios. The model revealed the grazing strategies respecting ecological and productive constraints specific to each scheme. Grazing strategies were assessed by both their ecological and productive performance. The viable control approach made it possible to obtain the whole set of viable grazing strategies and therefore to quantify the management flexibility of the grassland agroecosystem. Our results showed that habitat and result-oriented scenarios led to much higher ecological performance than the action-oriented one. Differences in both ecological and productive performance between the habitat and result-oriented scenarios were limited. Flexibility of the grassland agroecosystem in the result-oriented scenario was much higher than in that of habitat-oriented scenario. Our model confirms the higher flexibility as well as the better ecological and productive performance of result-oriented schemes. A larger use of result-oriented schemes in conservation may also allow farmers to adapt their management to local conditions and to climatic variations. PMID:22496746

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

    NASA Astrophysics Data System (ADS)

    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

  17. 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

  18. FMRP Regulates Neurotransmitter Release and Synaptic Information Transmission by Modulating Action Potential Duration via BK channels

    PubMed Central

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A.; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S.; Klyachko, Vitaly A.

    2013-01-01

    SUMMARY Loss of FMRP causes Fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely rescued in postnatal neurons. These presynaptic actions of FMRP are translation-independent and are mediated selectively by BK channels via interaction of FMRP with BK channel’s regulatory β4 subunits. Information-theoretical analysis demonstrates that loss of these FMRP functions causes marked dysregulation of synaptic information transmission. FMRP-dependent AP broadening is not limited to the hippocampus, but also occurs in cortical pyramidal neurons. Our results thus suggest major translation-independent presynaptic functions of FMRP that may have important implications for understanding FXS neuropathology. PMID:23439122

  19. Enhancers and their dynamics during hematopoietic differentiation and emerging strategies for therapeutic action.

    PubMed

    Cico, Alba; Andrieu-Soler, Charlotte; Soler, Eric

    2016-11-01

    Cellular differentiation requires precisely regulated tissue-specific and developmental stage-specific gene expression patterns. Numerous studies have highlighted the predictive power of enhancers on lineage-specific gene expression programs and have started to unravel their mechanisms of action. We review here the dynamics of the enhancer landscape during hematopoietic differentiation and how enhancers function in the context of the 3D organization of the genome. We further discuss the involvement of aberrant enhancer activity in human diseases and emerging strategies aiming at controlling enhancer activity and chromosome topology for therapeutic purposes.

  20. 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.

  1. 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.

  2. miR-19b Regulates Ventricular Action Potential Duration in Zebrafish

    PubMed Central

    Benz, Alexander; Kossack, Mandy; Auth, Dominik; Seyler, Claudia; Zitron, Edgar; Juergensen, Lonny; Katus, Hugo A.; Hassel, David

    2016-01-01

    Sudden cardiac death due to ventricular arrhythmias often caused by action potential duration (APD) prolongation is a common mode of death in heart failure (HF). microRNAs, noncoding RNAs that fine tune gene expression, are frequently dysregulated during HF, suggesting a potential involvement in the electrical remodeling process accompanying HF progression. Here, we identified miR-19b as an important regulator of heart function. Zebrafish lacking miR-19b developed severe bradycardia and reduced cardiac contractility. miR-19b deficient fish displayed increased sensitivity to AV-block, a characteristic feature of long QT syndrome in zebrafish. Patch clamp experiments from whole hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular APD caused by impaired repolarization. We found that miR-19b directly and indirectly regulates the expression of crucial modulatory subunits of cardiac ion channels, and thereby modulates AP duration and shape. Interestingly, miR-19b knockdown mediated APD prolongation can rescue a genetically induced short QT phenotype. Thus, miR-19b might represent a crucial modifier of the cardiac electrical activity, and our work establishes miR-19b as a potential candidate for human long QT syndrome. PMID:27805004

  3. 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

  4. 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

  5. Na+ current in presynaptic terminals of the crayfish opener cannot initiate action potentials

    PubMed Central

    2015-01-01

    Action potential (AP) propagation in presynaptic axons of the crayfish opener neuromuscular junction (NMJ) was investigated by simultaneously recording from a terminal varicosity and a proximal branch. Although orthodromically conducting APs could be recorded in terminals with amplitudes up to 70 mV, depolarizing steps in terminals to −20 mV or higher failed to fire APs. Patch-clamp recordings did detect Na+ current (INa) in most terminals. The INa exhibited a high threshold and fast activation rate. Local perfusion of Na+-free saline showed that terminal INa contributed to AP waveform by slightly accelerating the rising phase and increasing the peak amplitude. These findings suggest that terminal INa functions to “touch up” but not to generate APs. PMID:26561611

  6. 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.

  7. A Shab potassium channel contributes to action potential broadening in peptidergic neurons.

    PubMed

    Quattrocki, E A; Marshall, J; Kaczmarek, L K

    1994-01-01

    We have cloned the gene for a potassium channel, Aplysia Shab, that is expressed in the bag cell neurons of Aplysia. The voltage dependence and kinetics of the Aplysia Shab current in oocytes match those of IK2, one of the two delayed rectifiers in these neurons. Like IK2, but in contrast with other members of the Shab subfamily, the Aplysia Shab current inactivates within several hundred milliseconds. This inactivation occurs by a process whose properties do not match those previously described for C-type and N-type mechanisms. Neither truncation of the N-terminus nor block by tetraethylammonium alters the time course of inactivation. By incorporating the characteristics of Aplysia Shab into a computational model, we have shown how this current contributes to the normal enhancement of action potentials that occurs in the bag cell neurons at the onset of neuropeptide secretion.

  8. Action potential shape change in an electrically coupled network during propagation: a computer simulation.

    PubMed

    Buckingham, Steven D; Spencer, Andrew N

    2008-06-01

    We applied compartmental computer modeling to test a model of spike shape change in the jellyfish, Polyorchis penicillatus, to determine whether adaptive spike shortening can be attributed to the inactivation properties of a potassium channel. We modeled the jellyfish outer nerve-ring as a continuous linear segment, using ion channel and membrane properties derived in earlier studies. The model supported action potentials that shortened as they propagated away from the site of initiation and this was found to be largely independent of potassium channel inactivation. Spike broadening near the site of initiation was found to be due to a depolarization plateau that collapsed as two spikes spread from the point of initiation. The lifetime of this plateau was found to depend critically on the inward current flux and the space constant of the membrane. These data suggest that the spike shape changes may be due not only to potassium channel inactivation, but also to the passive properties of the membrane.

  9. Neuronal adaptation involves rapid expansion of the action potential initiation site

    PubMed Central

    Scott, Ricardo S.; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P.; Rusakov, Dmitri A.

    2014-01-01

    Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate granule cells adapt their spiking threshold to the kinetics of the ongoing dendrosomatic excitatory input by expanding the AP-initiation area away from the soma while also decelerating local axonal spikes. Dual-patch soma–axon recordings combined with axonal Na+ and Ca2+ imaging and biophysical modelling show that the underlying mechanism involves distance-dependent inactivation of axonal Na+ channels due to somatic depolarization propagating into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP propagation could provide activity-dependent control of cell excitability and spiking on a relatively rapid timescale. PMID:24851940

  10. Inhomogeneity of action potential waveshape assists frequency entrainment of cardiac pacemaker cells.

    PubMed

    Cloherty, S L; Lovell, N H; Celler, B G; Dokos, S

    2001-10-01

    In this paper, we have employed ionic models of sinoatrial node cells to investigate the synchronization of a pair of coupled cardiac pacemaker cells from central and peripheral regions of the sinoatrial node. The free-running cycle length of the cell models was perturbed using two independent techniques and the minimum coupling conductance required to achieve frequency entrainment was used to assess the relative ease with which various cell pairs achieve entrainment. The factors effecting entrainment were further investigated using single-cell models paced with an artificial biphasic coupling current. Our simulation results suggest that dissimilar cell types, those with largely different upstroke velocities entrain more easily, that is, they require less coupling conductance to achieve 1:1 frequency entrainment. We, therefore, propose that regional variation in action-potential waveshape within the sinoatrial node assists frequency synchronization in vivo.

  11. 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.

  12. BDNF mRNA abundance regulated by antidromic action potentials and AP-LTD in hippocampus.

    PubMed

    Bukalo, Olena; Lee, Philip R; Fields, R Douglas

    2016-12-02

    Action-potential-induced LTD (AP-LTD) is a form of synaptic plasticity that reduces synaptic strength in CA1 hippocampal neurons firing antidromically during sharp-wave ripples. This firing occurs during slow-wave sleep and quiet moments of wakefulness, which are periods of offline replay of neural sequences learned during encoding sensory information. Here we report that rapid and persistent down-regulation of different mRNA transcripts of the BDNF gene accompanies AP-LTD, and that AP-LTD is abolished in mice with the BDNF gene knocked out in CA1 hippocampal neurons. These findings increase understanding of the mechanism of AP-LTD and the cellular mechanisms of memory consolidation.

  13. Sequential dissection of multiple ionic currents in single cardiac myocytes under action potential-clamp

    PubMed Central

    Banyasz, Tamas; Horvath, Balazs; Jian, Zhong; Izu, Leighton T.; Chen-Izu, Ye

    2011-01-01

    The cardiac action potential (AP) is shaped by myriad ionic currents. In this study we develop an innovative AP-clamp Sequential Dissection technique to enable recording of multiple ionic currents in the single cell under AP-clamp. This new technique presents a significant step beyond the traditional way of recording only one current in any one cell. The ability to measure many currents in a single cell has revealed two hitherto unknown characteristics of the ionic currents in cardiac cells: coordination of currents within a cell and large variation of currents between cells. Hence, the AP-clamp Sequential Dissection method provides a unique and powerful tool for studying individual cell electrophysiology. PMID:21215755

  14. Sequential dissection of multiple ionic currents in single cardiac myocytes under action potential-clamp.

    PubMed

    Banyasz, Tamas; Horvath, Balazs; Jian, Zhong; Izu, Leighton T; Chen-Izu, Ye

    2011-03-01

    The cardiac action potential (AP) is shaped by myriad ionic currents. In this study, we develop an innovative AP-clamp Sequential Dissection technique to enable the recording of multiple ionic currents in the single cell under AP-clamp. This new technique presents a significant step beyond the traditional way of recording only one current in any one cell. The ability to measure many currents in a single cell has revealed two hitherto unknown characteristics of the ionic currents in cardiac cells: coordination of currents within a cell and large variation of currents between cells. Hence, the AP-clamp Sequential Dissection method provides a unique and powerful tool for studying individual cell electrophysiology.

  15. 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

  16. Effects of 4-aminopyridine on action potentials generation in mouse sinoauricular node strips

    PubMed Central

    Golovko, Vladimir; Gonotkov, Mikhail; Lebedeva, Elena

    2015-01-01

    The physiological role of Ito has yet to be clarified. The goal of this study is to investigate the possible contribution of the transient outward current (Ito) on the generation of transmembrane action potentials (APs) and the sensitivity of mouse sinoauricular node (SAN) cells to a 4-aminopyridine (4AP) as Ito blocker. The electrophysiological identification of cells was performed in the sinoauricular node artery area (nstrips = 38) of the subendocardial surface using microelectrode technique. In this study, for the first time, it was observed that dependence duration of action potential at the level of 20% repolarization (APD20) level under a 4AP concentration in the pacemaker SAN and auricular cells corresponds to a curve predicted by Hill’s equation. APD20 raised by 70% and spike duration of AP increased by 15–25%, when 4AP concentration was increased from 0.1 to 5.0 mmol/L. Auricular cells were found to be more sensitive to 4AP than true pacemaker cells. This was accompanied by a decrease in the upstroke velocity as compared to the control. Our data and previous findings in the literature lead us to hypothesize that the 4AP-sensitive current participates in the repolarization formation of pacemaker and auricular type cells. Thus, study concerning the inhibitory effects of lidocaine and TTX on APD20 can explain the phenomenon of the decrease in upstroke velocity, which, for the first time, was observed after exposure to 4AP. Duration of AP at the level of 20% repolarization (APD20) under a 4-AP concentration 0.5 mmol/L in the true pacemaker cells lengthen by 60–70% with a control. PMID:26156968

  17. Mechanism of alpha-2 adrenergic modulation of canine cardiac Purkinje action potential.

    PubMed

    Lee, H C; Cai, J J; Arnar, D O; Shibata, E F; Martins, J B

    1996-08-01

    We reported recently that stimulation of postjunctional alpha-2 adrenergic receptors prolongs the action potential durations (APD) of isolated canine Purkinje fibers. With standard microelectrode techniques, we examined the ionic mechanism through which alpha-2 adrenergic stimulation prolonged Purkinje APD, by measuring the effects of inhibitors of the various plateau currents on the alpha-2-mediated prolongation of APD. The alpha-2-specific agonist UK 14,304 (0.1 microM) prolonged the Purkinje APD at 50% repolarization and the APD at 90% repolarization, and these effects were inhibited by yohimbine (0.1 microM). The Purkinje APD at 50% repolarization and the APD at 90% repolarization were prolonged significantly with the transient outward potassium current inhibitor 4-aminopyridine (1 mM), the rapid component of delayed rectifier potassium current inhibitor d-sotalol (10 microM), the slow component of delayed rectifier potassium current inhibitor indapamide (0.1 microM) and the chloride current inhibitor mefenamic acid (10 nM) and were shortened significantly with the calcium current inhibitor nifedipine (0.3 microM). Prolongation of Purkinje APD at 50% repolarization and APD at 90% repolarization by UK 14,304 remained intact in the presence of d-sotalol, indapamide, mefenamic acid and nifedipine. All of these UK 14,304 effects were significantly reversed by yohimbine. Only in the presence of 4-aminopyridine did UK 14,304 fail to prolong Purkinje APD. The phase 1 magnitudes of Purkinje action potentials were also significantly inhibited by UK 14,304. This effect was completely abolished only in the presence of 4-aminopyridine. These results suggest that inhibition of the 4-aminopyridine-sensitive transient outward potassium current is the major ionic mechanism by which alpha-2 adrenergic stimulation prolongs Purkinje APD.

  18. 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

  19. Effects of norfluoxetine on the action potential and transmembrane ion currents in canine ventricular cardiomyocytes.

    PubMed

    Magyar, János; Szentandrássy, Norbert; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

    2004-09-01

    Norfluoxetine is the most important active metabolite of the widely used antidepressant compound fluoxetine. Although the cellular electrophysiological actions of fluoxetine are well characterized in cardiac cells, little is known about the effects of its metabolite. In this study, therefore, the effects of norfluoxetine on action potential (AP) configuration and transmembrane ion currents were studied in isolated canine cardiomyocytes using the whole cell configuration of patch clamp techniques. Micromolar concentrations of norfluoxetine (1-10 microM) modified AP configuration: amplitude and duration of the AP and maximum velocity of depolarization were decreased in addition to depression of the plateau and elimination of the incisura of AP. Voltage clamp experiments revealed a concentration-dependent suppression of both L-type Ca(2+) current, I(Ca) (EC(50)=1.13+/-0.08 microM) and transient outward K(+) current, I(to) (EC(50)=1.19+/-0.17 microM) having Hill coefficients close to unity. The midpoint potential of the steady-state inactivation of I(Ca) was shifted from -20.9+/-0.75 mV to -27.7+/-1.35 mV by 3 microM norfluoxetine ( P<0.05, n=7). No such shift in the steady-state inactivation curve was observed in the case of I(to). Similarly, norfluoxetine caused no change in the steady-state current-voltage relationship of the membrane or in the density of the inward rectifier K(+) current, I(K1). All these effects of norfluoxetine developed rapidly and were fully reversible. Comparing present results with those obtained previously with fluoxetine, it can be concluded that norfluoxetine displays stronger suppression of cardiac ion channels than fluoxetine. Consequently, the majority of the cardiac side effects observed during fluoxetine treatment are likely to be attributed to its metabolite norfluoxetine.

  20. Molecular dynamics study on microstructures of diblock copolymer melts with soft potential and potential recovery

    NASA Astrophysics Data System (ADS)

    Ryu, Ji Ho; Wee, Han Sol; Lee, Won Bo

    2016-09-01

    Various microstructures are obtained through the self-assembly of block copolymers on the basis of the compositional fractions and repulsive interactions among different types of beads. The inhomogeneity of block copolymers can be studied by molecular dynamics. However, preparing initial configurations of various self-assembled structures directly by molecular dynamics requires extensive computational time because of topological constraints. Furthermore, manual preparation often becomes a complicated and time-consuming procedure even for the simplest structures, such as a lamellar phase, not to mention three-dimensional bicontinuous cubic phases such as a gyroid phase. In this paper, this difficulty is overcome by using a soft potential, which allows the system to reach a self-assembled state quickly (within 3 τd ). Once a self-assembled microstructure is obtained, the normal potential is restored and equilibration steps are performed to enable the calculation of various properties of the microstructures. Various equilibrated phase structures—including S (spherical), H (hexagonal), G (gyroid), and L (lamellar) phases—are obtained by this approach. To verify our method, static and dynamic properties of the lamellar phase are examined and compared with previous results.

  1. Dynamical exchange-correlation potentials beyond the local density approximation

    NASA Astrophysics Data System (ADS)

    Tao, Jianmin; Vignale, Giovanni

    2006-03-01

    Approximations for the static exchange-correlation (xc) potential of density functional theory (DFT) have reached a high level of sophistication. By contrast, time-dependent xc potentials are still being treated in a local (although velocity-dependent) approximation [G. Vignale, C. A. Ullrich and S. Conti, PRL 79, 4879 (1997)]. Unfortunately, one of the assumptions upon which the dynamical local approximation is based appears to break down in the important case of d.c. transport. Here we propose a new approximation scheme, which should allow a more accurate treatment of molecular transport problems. As a first step, we separate the exact adiabatic xc potential, which has the same form as in the static theory and can be treated by a generalized gradient approximation (GGA) or a meta-GGA. In the second step, we express the high-frequency limit of the xc stress tensor (whose divergence gives the xc force density) in terms of the exact static xc energy functional. Finally, we develop a perturbative scheme for the calculation of the frequency dependence of the xc stress tensor in terms of the ground-state Kohn-Sham orbitals and eigenvalues.

  2. Potential of an outranking multi-criteria approach to support the participatory assessment of land management actions.

    PubMed

    Ocampo-Melgar, Anahí; Bautista, Susana; Edward deSteiguer, J; Orr, Barron J

    2016-12-07

    We evaluated the potential of an outranking Multi-Criteria Decision Analysis approach for assisting in the participatory assessment of dryland management actions implemented in the San Simon watershed, in southeastern Arizona, USA. We compared an outranking-facilitated assessment of actions with a simple and direct (baseline) ranking of the same actions by the participating stakeholders in terms of: 1) internal homogeneity of each assessment approach, (2) similarity of individual assessments between methods, and (3) effects of the use of implicit/explicit assessment criteria. The actions assessed combined various management approaches, including livestock management (rotation, resting), vegetation management (grass seeding, brush control), and hydraulic structures (dams, dykes). The outranking-facilitated assessment discriminated better between actions and reduced the variability of results between individual stakeholders as compared with the direct ranking of actions. In general, the two assessments significantly differed in the relative preference of the five management actions assessed, yet both assessments identified rotational grazing combined with vegetation management (grass seeding and brush control) as the most preferred management action in the study area. The comparative analysis revealed inconsistencies between the use of implicit and explicit assessment criteria. Our findings highlight the opportunities offered by outranking approaches to help capture, structure, and make explicit stakeholder perspectives in the framework of a participatory environmental assessment process, which may facilitate the understanding of the multiple preferences involved. The outranking integration process, which resembles a voting procedure, proved simple and transparent, with potential for contributing to stakeholder engagement and trust in participatory assessment.

  3. Dynamic root exudation of sorgoleone and its in planta mechanism of action

    PubMed Central

    Dayan, Franck E.; Howell, J'Lynn; Weidenhamer, Jeffrey D.

    2009-01-01

    The oily droplets exuded from the root hairs of sorghum are composed of a 1:1 ratio of sorgoleone and its lipid resorcinol analogue. The production of these droplets appears to be suppressed when c. 20 μg of exudate mg−1 root dry weight accumulates at the tip of the root hairs. However, more exudate is produced following gentle washing of the roots with water, suggesting that the biosynthesis of lipid benzoquinones and resorcinols is a dynamic process. Sorgoleone interferes with several molecular target sites, including photosynthetic electron transport, in in vitro assays. However, the in planta mechanism of action of sorgoleone remains controversial because it is not clear whether this lipid benzoquinone exuding from the roots of sorghum is taken up by roots of the receiving plants and translocated to their foliage where it must enter the chloroplast and inhibit PSII in the thylakoid membrane. Experiments designed to test the in planta mode of action of sorgoleone demonstrated that it has no effect on the photosynthesis of older plants, but inhibits photosynthesis in germinating seedlings. Sorgoleone is not translocated acropetally in older plants, but can be absorbed through the hypocotyl and cotyledonary tissues. Therefore, the mode of action of sorgoleone may be the result of inhibition of photosynthesis in young seedlings in concert with inhibition of its other molecular target sites in older plants. PMID:19357432

  4. Dynamic Cascades with Bidirectional Bootstrapping for Action Unit Detection in Spontaneous Facial Behavior

    PubMed Central

    Zhu, Yunfeng; De la Torre, Fernando; Cohn, Jeffrey F.; Zhang, Yu-Jin

    2015-01-01

    Automatic facial action unit detection from video is a long-standing problem in facial expression analysis. Research has focused on registration, choice of features, and classifiers. A relatively neglected problem is the choice of training images. Nearly all previous work uses one or the other of two standard approaches. One approach assigns peak frames to the positive class and frames associated with other actions to the negative class. This approach maximizes differences between positive and negative classes, but results in a large imbalance between them, especially for infrequent AUs. The other approach reduces imbalance in class membership by including all target frames from onsets to offsets in the positive class. However, because frames near onsets and offsets often differ little from those that precede them, this approach can dramatically increase false positives. We propose a novel alternative, dynamic cascades with bidirectional bootstrapping (DCBB), to select training samples. Using an iterative approach, DCBB optimally selects positive and negative samples in the training data. Using Cascade Adaboost as basic classifier, DCBB exploits the advantages of feature selection, efficiency, and robustness of Cascade Adaboost. To provide a real-world test, we used the RU-FACS (a.k.a. M3) database of nonposed behavior recorded during interviews. For most tested action units, DCBB improved AU detection relative to alternative approaches. PMID:26576248

  5. Potential Vorticity and Diabatic Processes in Frontal Dynamics.

    NASA Astrophysics Data System (ADS)

    Montgomery, Michael Thomas

    1990-01-01

    In a two part study I investigate the role of potential vorticity anomalies in surface frontogenesis in both a dry and moist semi-geostrophic Eady model. Dry frontal dynamics is considered in Part one where I demonstrate rapid surface frontal formation for properly configured small disturbances even at zonal wavenumbers for which no exponentially unstable modes exist. While lack of exponential growth does not preclude frontal development the strength of the disturbance must exceed an amplitude threshold for frontal formation. In practice the finite amplitude constraint is not severe as it requires meridional winds of only a few meters per second. Part II explores surface frontogenesis in the presence of latent heat release using a generalization of the 2D Eady model that insures that the heating term gives correct asymptotic behavior at high and low temperatures. A variety of initial conditions are considered in which upper level potential vorticity disturbances induce strong positive potential vorticity anomalies near the lower surface. With uniform interior potential vorticity, baroclinic coupling between the upper disturbance and the induced surface disturbance is weak despite the near neutrality to slantwise convection. On the other hand examples of initial disturbances with interior potential vorticity show greatly enhanced baroclinic coupling between upper and lower disturbances. Comparison with observation suggests these represent a simple phenomenological description of squall line development. I also find that latent heat release destabilizes surface concentrated neutral disturbances that do not intensify in the dry problem. These frontal developments are not primarily baroclinic. Rather, the source of energy is conversion of latent heat into kinetic energy in ascent regions through generation of surface potential vorticity. Development is slow in comparison to baroclinic frontogenesis but is not crucially dependent on the presence of large amplitude

  6. Dynamical Control of Matter-Wave Tunneling in Periodic Potentials

    NASA Astrophysics Data System (ADS)

    Lignier, H.; Sias, C.; Ciampini, D.; Singh, Y.; Zenesini, A.; Morsch, O.; Arimondo, E.

    2007-11-01

    We report on measurements of dynamical suppression of interwell tunneling of a Bose-Einstein condensate (BEC) in a strongly driven optical lattice. The strong driving is a sinusoidal shaking of the lattice corresponding to a time-varying linear potential, and the tunneling is measured by letting the BEC freely expand in the lattice. The measured tunneling rate is reduced and, for certain values of the shaking parameter, completely suppressed. Our results are in excellent agreement with theoretical predictions. Furthermore, we have verified that, in general, the strong shaking does not destroy the phase coherence of the BEC, opening up the possibility of realizing quantum phase transitions by using the shaking strength as the control parameter.

  7. Action potential broadening induced by lithium may cause a presynaptic enhancement of excitatory synaptic transmission in neonatal rat hippocampus.

    PubMed

    Colino, A; García-Seoane, J J; Valentín, A

    1998-07-01

    Lithium enhances excitatory synaptic transmission in CA1 pyramidal cells, but the mechanisms remain unclear. The present study demonstrates that lithium enhances the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA) receptor-mediated components of the excitatory postsynaptic current (EPSC). Lithium decreased the magnitude of paired-pulse facilitation and presented an inverse correlation between the lithium-induced enhancement of synaptic transmission and initial paired-pulse facilitation, which is consistent with a presynaptic mode of action. The enhancement of synaptic strength is likely to act, at least in part, by increasing the amplitude of the presynaptic Ca2+ transient. One mechanism which could account for this change of the presynaptic Ca2+ transient is an increase in the duration of the action potential. We investigated action potential in hippocampal pyramidal neurons and found that lithium (0.5-6 mM) increased the half-amplitude duration and reduced the rate of repolarization, whereas the rate of depolarization remained similar. To find out whether the lithium synaptic effects might be explained by spike broadening, we investigated the field recording of the excitatory postsynaptic potential (EPSP) in hippocampal slices and found three lines of evidence. First, the prolongation of the presynaptic action potential with 4-aminopyridine and tetraethylammonium blocked or reduced the synaptic effects of lithium. Second, the lithium-induced synaptic enhancement was modulated when presynaptic Ca2+ influx was varied by changing the external Ca2+ concentration. Finally, both effects, the synaptic transmission increment and the action potential broadening, were independent of inositol depletion. These results suggest that lithium enhances synaptic transmission in the hippocampus via a presynaptic site of action: the mechanism underlying the potentiating effect may be attributable to an increased Ca2+ influx consequent

  8. Profile of I(Ks) during the action potential questions the therapeutic value of I(Ks) blockade.

    PubMed

    Bányász, Tamás; Koncz, Roland; Fülöp, László; Szentandrássy, Norbert; Magyar, János; Nánási, Péter P

    2004-01-01

    The goal of this paper is two fold. First, we attempt to review the reports available on the role of I(Ks) in myocardial repolarization. Based on theoretical considerations and experimental results, it seems reasonable to assume that I(Ks)blockade will lengthen the action potential. However, results obtained with I(Ks) blockers, like chromanol 293B or L-735,821, are conflicting, since from slight lengthening to marked prolongation of action potentials were equally obtained. Although these contradictory results were explained by interspecies or regional differences, the role of I(Ks) in repolarization is a matter of growing dispute. In the second part of this study, we simulated the performance of I(Ks) during cardiac action potentials. We compared the profile of the predicted current in three mathematical models in order to determine the relative role of the current in repolarization. We studied the effect of the cycle length, action potential duration and height of the plateau on the profile of I(Ks) in epicardiac, endocardiac and midmyocardiac ventricular action potentials. The results indicate that the height of the plateau is the most important parameter to control activation of I(Ks)in cardiac tissues, and accordingly, the interspecies and regional differences observed in the efficacy of I(Ks) blockers are likely due to the known differences in action potential morphology. We conclude also that I(Ks)blockade may have unpredictable effects on the length of the action potential in a diseased heart, questioning the possible therapeutic value of drugs blocking I(Ks).

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

    PubMed

    Brunner, János; Szabadics, János

    2016-10-05

    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.

  10. Role of dendritic spines in action potential backpropagation: a numerical simulation study.

    PubMed

    Tsay, David; Yuste, Rafael

    2002-11-01

    Two remarkable aspects of pyramidal neurons are their complex dendritic morphologies and the abundant presence of spines, small structures that are the sites of excitatory input. Although the channel properties of the dendritic shaft membrane have been experimentally probed, the influence of spine properties in dendritic signaling and action potential propagation remains unclear. To explore this we have performed multi-compartmental numerical simulations investigating the degree of consistency between experimental data on dendritic channel densities and backpropagation behavior, as well as the necessity and degree of influence of excitable spines. Our results indicate that measured densities of Na(+) channels in dendritic shafts cannot support effective backpropagation observed in apical dendrites due to suprathreshold inactivation. We demonstrate as a potential solution that Na(+) channels in spines at higher densities than those measured in the dendritic shaft can support extensive backpropagation. In addition, clustering of Na(+) channels in spines appears to enhance their effect due to their unique morphology. Finally, we show that changes in spine morphology significantly influence backpropagation efficacy. These results suggest that, by clustering sodium channels, spines may serve to control backpropagation.

  11. Seasonal acclimatization of the cardiac action potential in the Arctic navaga cod (Eleginus navaga, Gadidae).

    PubMed

    Hassinen, Minna; Abramochkin, Denis V; Vornanen, Matti

    2014-04-01

    Freshwater fishes of north-temperate latitudes adjust electrical excitability of the heart to seasonal temperature changes by changing expression levels of ion channel isoforms. However, little is known about thermal responses of action potential (AP) in the hearts of marine polar fishes. To this end, we examined cardiac AP in the atrial myocardium of the Arctic navaga cod (Eleginus navaga) from the White Sea (Russia) acclimatized to winter (March) and summer (September) seasons. Acute increases in temperature from 4 to 10 °C were associated with increases in heart rate, maximum velocity of AP upstroke and negative resting membrane potential, while duration of AP was shortened in both winter-acclimatized and summer-acclimatized navaga hearts. In winter, there was a compensatory shortening (41.1%) of atrial AP duration and this was associated with a strong increase in transcript expression of Erg K(+) channels, known to produce the rapid component of the delayed rectifier K(+) current, I(Kr). Smaller increases were found in the expression of Kir2.1 channels that produce the inward rectifier K(+) current, I(K1). These findings indicate that the heart of navaga cod has a good acclimatory capacity in electrical excitation of cardiac myocytes, which enables cardiac function in the cold-eurythermal waters of the subarctic White Sea.

  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. 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.

  14. Zinc-related actions of sublethal levels of benzalkonium chloride: Potentiation of benzalkonium cytotoxicity by zinc.

    PubMed

    Mitani, Tsuyoshi; Elmarhomy, Ahmed Ibrahim Elhossany; Dulamjav, Luvsandorj; Anu, Enkhtumur; Saitoh, Shohei; Ishida, Shiro; Oyama, Yasuo

    2017-04-25

    Benzalkonium chloride (BZK) is a common preservative used in pharmaceutical and personal care products. ZnCl2 was recently reported to significantly potentiate the cytotoxicity of some biocidal compounds. In the present study, therefore, we compared the cytotoxic potency of BZK and then further studied the Zn(2+)-related actions of the most cytotoxic agent among BZK, using flow cytometric techniques with appropriate fluorescent probes in rat thymocytes. Cytotoxicity of benzylcetyldimethylammonium (BZK-C16) was more potent that those of benzyldodecyldimethylammonium and benzyldimethyltetradecylammonium. ZnCl2 (1-10 μM) significantly potentiated the cytotoxicity of BZK-C16 at a sublethal concentration (1 μM). The co-treatment of cells with 3 μM ZnCl2 and 1 μM BZK-C16 increased the population of both living cells with phosphatidylserine exposed on membrane surfaces and dead cells. BZK-C16 at 0.3-1.0 μM elevated intracellular Zn(2+) levels by increasing Zn(2+) influx, and augmented the cytotoxicity of 100 μM H2O2. Zn(2+) is concluded to facilitate the toxicity of BZK. We suggest that the toxicity of BZK is determined after taking extracellular (plasma) and/or environmental Zn(2+) levels into account.

  15. Glutamate induces series of action potentials and a decrease in circumnutation rate in Helianthus annuus.

    PubMed

    Stolarz, Maria; Król, Elzbieta; Dziubińska, Halina; Kurenda, Andrzej

    2010-03-01

    Reports concerning the function of glutamate (Glu) in the electrical and movement phenomena in plants are scarce. Using the method of extracellular measurement, we recorded electrical potential changes in the stem of 3-week-old Helianthus annuus L. plants after injection of Glu solution. Simultaneously, circumnutation movements of the stem were measured with the use of time-lapse images. Injection of Glu solution at millimolar (200, 50, 5 mM) concentrations in the basal part of the stem evoked a series of action potentials (APs). The APs appeared in the site of injection and in different parts of the stem and were propagated acropetally and/or basipetally along the stem. Glu injection also resulted in a transient, approximately 5-h-long decrease in the stem circumnutation rate. The APs initiated and propagating in the sunflower stem after Glu injection testify the existence of a Glu perception system in vascular plants and suggest its involvement in electrical, long-distance signaling. Our experiments also demonstrated that Glu is a factor affecting circumnutation movements.

  16. 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

  17. A fluorescent, genetically-encoded voltage probe capable of resolving action potentials.

    PubMed

    Barnett, Lauren; Platisa, Jelena; Popovic, Marko; Pieribone, Vincent A; Hughes, Thomas

    2012-01-01

    There is a pressing need in neuroscience for genetically-encoded, fluorescent voltage probes that can be targeted to specific neurons and circuits to allow study of neural activity using fluorescent imaging. We created 90 constructs in which the voltage sensing portion (S1-S4) of Ciona intestinalis voltage sensitive phosphatase (CiVSP) was fused to circularly permuted eGFP. This led to ElectricPk, a probe that is an order of magnitude faster (taus ~1-2 ms) than any currently published fluorescent protein-based voltage probe. ElectricPk can follow the rise and fall of neuronal action potentials with a modest decrease in fluorescence intensity (~0.7% ΔF/F). The probe has a nearly linear fluorescence/membrane potential response to both hyperpolarizing and depolarizing steps. This is the first probe based on CiVSP that captures the rapid movements of the voltage sensor, suggesting that voltage probes designed with circularly permuted fluorescent proteins may have some advantages.

  18. Amplitudes of sural and radial sensory nerve action potentials in orthodromic and antidromic studies in children.

    PubMed

    Melendrez, J L; MacMillan, L J; Vajsar, J

    1998-01-01

    Several previous studies of adults have reported that the amplitudes of the sural and superficial radial nerve action potentials (SN and SRN SNAP respectively) are larger with antidromic than with orthodromic recordings. However, this difference has not been documented in children. This study evaluated the amplitudes of SN and SRN SNAPs obtained with antidromic and orthodromic recordings in children with and without neuropathy and compared these data with findings in adults. The SN or SRN or both of 10 neurologically normal children, 6 children with neuropathy and 7 healthy adults were studied with surface stimulation and recording. The position of the stimulating and recording electrodes for the orthodromic recordings was the reverse of that for the antidromic recordings. Peak-to-peak SNAP amplitudes were measured and analyzed. The mean of the SRN SNAP amplitude was significantly higher with the antidromic than the orthodromic technique for the first and third groups (p < 0.05). The mean SN SNAP amplitude was higher in the three groups, but not statistically significant when the data for the children and adult normal groups were combined and reanalyzed (p < 0.05). Consistent responses were obtained with both techniques. However, the antidromic technique was superior to the orthodromic technique because of the greater amplitude of responses. We recommend the use of the antidromic technique because of its greater amplitudes, ease of use and potential reduction of discomfort to the patient.

  19. 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

  20. ζ-potential determination using a ZetaMeter-Dynamic Speckle assembly

    NASA Astrophysics Data System (ADS)

    González-Peña, Rolando J.; Sánchez-Muñoz, Orlando L.; Martínez-Celorio, René A.; Cibrián, Rosa M.; Salvador-Palmer, Rosario; Salgado, Jesús

    2012-10-01

    Electrophoretic mobility and ζ-potential are important physical parameters for the characterization of micro- and nanosystems. In this communication we describe a new method for determining the ζ-potential through the assembly of two well known techniques: free electrophoresis and Dynamic Speckle. When coherent light passes through a fluid having scattering centres, the far field interference originates a speckled image. If the scattering centres are contained within the cylindrical electrophoresis cell of a ZetaMeter and are forced to move in an orderly way under the action of an external electric field, the time variation of the light intensity in the far field speckle images follows a temporal autocorrelation function g(τ). The corresponding correlation time can then be obtained and related with the velocity, from which the electrophoretic mobility and the ζ-potential of the scattering centres can be determined. We have applied this method to microparticles, like natural air-floated silica and two classes of bioceramics, hydroxyapatite and biphasic calcium phosphate. For comparison, we analysed the same samples in parallel using a commercial Zetasizer Nano from Malvern Instruments. The values of ζ-potential determined using the two techniques were the same within ~3% error. These results validate our new method as a useful and efficient alternative for ζ-potential determination of particles, at least within the micrometer scale.

  1. The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF

    PubMed Central

    Schuliga, Michael; Jaffar, Jade; Harris, Trudi; Knight, Darryl A; Westall, Glen; Stewart, Alastair G

    2017-01-01

    The role of urokinase plasminogen activator (uPA) in idiopathic pulmonary fibrosis (IPF) remains unclear. uPA-generated plasmin has potent fibrogenic actions involving protease activated receptor-1 (PAR-1) and interleukin-6 (IL-6). Here we characterize uPA distribution or levels in lung tissue and sera from IPF patients to establish the mechanism of its fibrogenic actions on lung fibroblasts (LFs). uPA immunoreactivity was detected in regions of fibrosis including fibroblasts of lung tissue from IPF patients (n = 7). Serum uPA levels and activity were also higher in IPF patients (n = 18) than controls (n = 18) (P < 0.05), being negatively correlated with lung function as measured by forced vital capacity (FVC) %predicted (P < 0.05). The culture supernatants of LFs from IPF patients, as compared to controls, showed an increase in plasmin activity after plasminogen incubation (5–15 μg/mL), corresponding with increased levels of uPA and IL-6 (n = 5–6, P < 0.05). Plasminogen-induced increases in plasmin activity and IL-6 levels were attenuated by reducing uPA and/or PAR-1 expression by RNAi. Plasmin(ogen)-induced mitogenesis was also attenuated by targeting uPA, PAR-1 or IL-6. Our data shows uPA is formed in active regions of fibrosis in IPF lung and contributes to LF plasmin generation, IL-6 production and proliferation. Urokinase is a potential target for the treatment of lung fibrosis. PMID:28139758

  2. Actions in the Eye: Dynamic Gaze Datasets and Learnt Saliency Models for Visual Recognition.

    PubMed

    Mathe, Stefan; Sminchisescu, Cristian

    2015-07-01

    Systems based on bag-of-words models from image features collected at maxima of sparse interest point operators have been used successfully for both computer visual object and action recognition tasks. While the sparse, interest-point based approach to recognition is not inconsistent with visual processing in biological systems that operate in `saccade and fixate' regimes, the methodology and emphasis in the human and the computer vision communities remains sharply distinct. Here, we make three contributions aiming to bridge this gap. First, we complement existing state-of-the art large scale dynamic computer vision annotated datasets like Hollywood-2 [1] and UCF Sports [2] with human eye movements collected under the ecological constraints of visual action and scene context recognition tasks. To our knowledge these are the first large human eye tracking datasets to be collected and made publicly available for video, vision.imar.ro/eyetracking (497,107 frames, each viewed by 19 subjects), unique in terms of their (a) large scale and computer vision relevance, (b) dynamic, video stimuli, (c) task control, as well as free-viewing. Second, we introduce novel dynamic consistency and alignment measures, which underline the remarkable stability of patterns of visual search among subjects. Third, we leverage the significant amount of collected data in order to pursue studies and build automatic, end-to-end trainable computer vision systems based on human eye movements. Our studies not only shed light on the differences between computer vision spatio-temporal interest point image sampling strategies and the human fixations, as well as their impact for visual recognition performance, but also demonstrate that human fixations can be accurately predicted, and when used in an end-to-end automatic system, leveraging some of the advanced computer vision practice, can lead to state of the art results.

  3. Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation

    PubMed Central

    Goldberg, Jesse H; Tamas, Gabor; Yuste, Rafael

    2003-01-01

    GABAergic interneurones are essential in cortical processing, yet the functional properties of their dendrites are still poorly understood. In this first study, we combined two-photon calcium imaging with whole-cell recording and anatomical reconstructions to examine the calcium dynamics during action potential (AP) backpropagation in three types of V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). Somatically generated APs actively backpropagated into the dendritic tree and evoked instantaneous calcium accumulations. Although voltage-gated calcium channels were expressed throughout the dendritic arbor, calcium signals during backpropagation of both single APs and AP trains were restricted to proximal dendrites. This spatial control of AP backpropagation was mediated by Ia-type potassium currents and could be mitigated by by previous synaptic activity. Further, we observed supralinear summation of calcium signals in synaptically activated dendritic compartments. Together, these findings indicate that in interneurons, dendritic AP propagation is synaptically regulated. We propose that interneurones have a perisomatic and a distal dendritic functional compartment, with different integrative functions. PMID:12844506

  4. Role of the Alternans of Action Potential Duration and Aconitine-Induced Arrhythmias in Isolated Rabbit Hearts

    PubMed Central

    Jung, Byung-Chun; Lee, Sang-Hee; Cho, Yong-Keun; Park, Hyoung-Seob; Kim, Yoon-Nyun; Lee, Young-Soo

    2011-01-01

    Under conditions of Na+ channel hyperactivation with aconitine, the changes in action potential duration (APD) and the restitution characteristics have not been well defined in the context of aconitine-induced arrhythmogenesis. Optical mapping of voltage using RH237 was performed with eight extracted rabbit hearts that were perfused using the Langendorff system. The characteristics of APD restitution were assessed using the steady-state pacing protocol at baseline and 0.1 µM aconitine concentration. In addition, pseudo-ECG was analyzed at baseline, and with 0.1 and 1.0 µM of aconitine infusion respectively. Triggered activity was not shown in dose of 0.1 µM aconitine but overtly presented in 1.0 µM of aconitine. The slopes of the dynamic APD restitution curves were significantly steeper with 0.1 µM of aconitine than at baseline. With aconitine administration, the cycle length of initiation of APD alternans was significantly longer than at baseline (287.5 ± 9.6 vs 247.5 ± 15.0 msec, P = 0.016). The functional reentry following regional conduction block appears with the progression of APD alternans. Ventricular fibrillation is induced reproducibly at pacing cycle length showing a 2:1 conduction block. Low-dose aconitine produces arrhythmogenesis at an increasing restitution slope with APD alternans as well as regional conduction block that proceeds to functional reentry. PMID:22147994

  5. Action potential initiation in a two-compartment model of pyramidal neuron mediated by dendritic Ca(2+) spike.

    PubMed

    Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

    2017-04-03

    Dendritic Ca(2+) spike endows cortical pyramidal cell with powerful ability of synaptic integration, which is critical for neuronal computation. Here we propose a two-compartment conductance-based model to investigate how the Ca(2+) activity of apical dendrite participates in the action potential (AP) initiation to affect the firing properties of pyramidal neurons. We have shown that the apical input with sufficient intensity triggers a dendritic Ca(2+) spike, which significantly boosts dendritic inputs as it propagates to soma. Such event instantaneously shifts the limit cycle attractor of the neuron and results in a burst of APs, which makes its firing rate reach a plateau steady-state level. Delivering current to two chambers simultaneously increases the level of neuronal excitability and decreases the threshold of input-output relation. Here the back-propagating APs facilitate the initiation of dendritic Ca(2+) spike and evoke BAC firing. These findings indicate that the proposed model is capable of reproducing in vitro experimental observations. By determining spike initiating dynamics, we have provided a fundamental link between dendritic Ca(2+) spike and output APs, which could contribute to mechanically interpreting how dendritic Ca(2+) activity participates in the simple computations of pyramidal neuron.

  6. 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.

  7. Toward panoramic in situ mapping of action potential propagation in transgenic hearts to investigate initiation and therapeutic control of arrhythmias

    PubMed Central

    Dura, Miroslav; Schröder-Schetelig, Johannes; Luther, Stefan; Lehnart, Stephan E.

    2014-01-01

    To investigate the dynamics and propensity for arrhythmias in intact transgenic hearts comprehensively, optical strategies for panoramic fluorescence imaging of action potential (AP) propagation are essential. In particular, mechanism-oriented molecular studies usually depend on transgenic mouse hearts of only a few millimeters in size. Furthermore, the temporal scales of the mouse heart remain a challenge for panoramic fluorescence imaging with heart rates ranging from 200 min−1 (e.g., depressed sinus node function) to over 1200 min−1 during fast arrhythmias. To meet these challenging demands, we and others developed physiologically relevant mouse models and characterized their hearts with planar AP mapping. Here, we summarize the progress toward panoramic fluorescence imaging and its prospects for the mouse heart. In general, several high-resolution cameras are synchronized and geometrically arranged for panoramic voltage mapping and the surface and blood vessel anatomy documented through image segmentation and heart surface reconstruction. We expect that panoramic voltage imaging will lead to novel insights about molecular arrhythmia mechanisms through quantitative strategies and organ-representative analysis of intact mouse hearts. PMID:25249982

  8. Action potential initiation in a two-compartment model of pyramidal neuron mediated by dendritic Ca2+ spike

    PubMed Central

    Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

    2017-01-01

    Dendritic Ca2+ spike endows cortical pyramidal cell with powerful ability of synaptic integration, which is critical for neuronal computation. Here we propose a two-compartment conductance-based model to investigate how the Ca2+ activity of apical dendrite participates in the action potential (AP) initiation to affect the firing properties of pyramidal neurons. We have shown that the apical input with sufficient intensity triggers a dendritic Ca2+ spike, which significantly boosts dendritic inputs as it propagates to soma. Such event instantaneously shifts the limit cycle attractor of the neuron and results in a burst of APs, which makes its firing rate reach a plateau steady-state level. Delivering current to two chambers simultaneously increases the level of neuronal excitability and decreases the threshold of input-output relation. Here the back-propagating APs facilitate the initiation of dendritic Ca2+ spike and evoke BAC firing. These findings indicate that the proposed model is capable of reproducing in vitro experimental observations. By determining spike initiating dynamics, we have provided a fundamental link between dendritic Ca2+ spike and output APs, which could contribute to mechanically interpreting how dendritic Ca2+ activity participates in the simple computations of pyramidal neuron. PMID:28367964

  9. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease.

    PubMed

    Williams, Robert J; Spencer, Jeremy P E

    2012-01-01

    There is increasing evidence that the consumption of flavonoid-rich foods can beneficially influence normal cognitive function. In addition, a growing number of flavonoids have been shown to inhibit the development of Alzheimer disease (AD)-like pathology and to reverse deficits in cognition in rodent models, suggestive of potential therapeutic utility in dementia. The actions of flavonoid-rich foods (e.g., green tea, blueberry, and cocoa) seem to be mediated by the direct interactions of absorbed flavonoids and their metabolites with a number of cellular and molecular targets. For example, their specific interactions within the ERK and PI3-kinase/Akt signaling pathways, at the level of receptors or kinases, have been shown to increase the expression of neuroprotective and neuromodulatory proteins and increase the number of, and strength of, connections between neurons. Concurrently, their effects on the vascular system may also lead to enhancements in cognitive performance through increased brain blood flow and an ability to initiate neurogenesis in the hippocampus. Additional mechanisms have been suggested for the ability of flavonoids to delay the initiation of and/or slow the progression of AD-like pathology and related neurodegenerative disorders, including a potential to inhibit neuronal apoptosis triggered by neurotoxic species (e.g., oxidative stress and neuroinflammation) or disrupt amyloid β aggregation and effects on amyloid precursor protein processing through the inhibition of β-secretase (BACE-1) and/or activation of α-secretase (ADAM10). Together, these processes act to maintain the number and quality of synaptic connections in key brain regions and thus flavonoids have the potential to prevent the progression of neurodegenerative pathologies and to promote cognitive performance.

  10. Averaging methods for extracting representative waveforms from motor unit action potential trains.

    PubMed

    Malanda, Armando; Navallas, Javier; Rodriguez-Falces, Javier; Rodriguez-Carreño, Ignacio; Gila, Luis

    2015-08-01

    In the context of quantitative electromyography (EMG), it is of major interest to obtain a waveform that faithfully represents the set of potentials that constitute a motor unit action potential (MUAP) train. From this waveform, various parameters can be determined in order to characterize the MUAP for diagnostic analysis. The aim of this work was to conduct a thorough, in-depth review, evaluation and comparison of state-of-the-art methods for composing waveforms representative of MUAP trains. We evaluated nine averaging methods: Ensemble (EA), Median (MA), Weighted (WA), Five-closest (FCA), MultiMUP (MMA), Split-sweep median (SSMA), Sorted (SA), Trimmed (TA) and Robust (RA) in terms of three general-purpose signal processing figures of merit (SPMF) and seven clinically-used MUAP waveform parameters (MWP). The convergence rate of the methods was assessed as the number of potentials per MUAP train (NPM) required to reach a level of performance that was not significantly improved by increasing this number. Test material comprised 78 MUAP trains obtained from the tibialis anterioris of seven healthy subjects. Error measurements related to all SPMF and MWP parameters except MUAP amplitude descended asymptotically with increasing NPM for all methods. MUAP amplitude showed a consistent bias (around 4% for EA and SA and 1-2% for the rest). MA, TA and SSMA had the lowest SPMF and MWP error figures. Therefore, these methods most accurately preserve and represent MUAP physiological information of utility in clinical medical practice. The other methods, particularly WA, performed noticeably worse. Convergence rate was similar for all methods, with NPM values averaged among the nine methods, which ranged from 10 to 40, depending on the waveform parameter evaluated.

  11. Potential-dependent dynamic fracture of nanoporous gold.

    PubMed

    Sun, Shaofeng; Chen, Xiying; Badwe, Nilesh; Sieradzki, Karl

    2015-09-01

    When metallic alloys are exposed to a corrosive environment, porous nanoscale morphologies spontaneously form that can adversely affect the mechanical integrity of engineered structures. This form of stress-corrosion cracking is responsible for the well-known 'season cracking' of brass and stainless steel components in nuclear power generating stations. One explanation for this is that a high-speed crack is nucleated within the porous layer, which subsequently injects into non-porous parent-phase material. We study the static and dynamic fracture properties of free-standing monolithic nanoporous gold as a function electrochemical potential using high-speed photography and digital image correlation. The experiments reveal that at electrochemical potentials typical of porosity formation these structures are capable of supporting dislocation-mediated plastic fracture at crack velocities of 200 m s(-1). Our results identify the important role of high-speed fracture in stress-corrosion cracking and are directly applicable to the behaviour of monolithic dealloyed materials at present being considered for a variety of applications.

  12. Potential-dependent dynamic fracture of nanoporous gold

    NASA Astrophysics Data System (ADS)

    Sun, Shaofeng; Chen, Xiying; Badwe, Nilesh; Sieradzki, Karl

    2015-09-01

    When metallic alloys are exposed to a corrosive environment, porous nanoscale morphologies spontaneously form that can adversely affect the mechanical integrity of engineered structures. This form of stress-corrosion cracking is responsible for the well-known `season cracking’ of brass and stainless steel components in nuclear power generating stations. One explanation for this is that a high-speed crack is nucleated within the porous layer, which subsequently injects into non-porous parent-phase material. We study the static and dynamic fracture properties of free-standing monolithic nanoporous gold as a function electrochemical potential using high-speed photography and digital image correlation. The experiments reveal that at electrochemical potentials typical of porosity formation these structures are capable of supporting dislocation-mediated plastic fracture at crack velocities of 200 m s-1. Our results identify the important role of high-speed fracture in stress-corrosion cracking and are directly applicable to the behaviour of monolithic dealloyed materials at present being considered for a variety of applications.

  13. Suited Occupant Injury Potential During Dynamic Spacecraft Flight Phases

    NASA Technical Reports Server (NTRS)

    Dub, Mark O.; McFarland, Shane M.

    2010-01-01

    In support of the Constellation Space Suit Element [CSSE], a new space-suit architecture will be created for support of Launch, Entry, Abort, Microgravity Extra- Vehicular Activity [EVA], and post-landing crew operations, safety and, under emergency conditions, survival. The space suit is unique in comparison to previous launch, entry, and abort [LEA] suit architectures in that it utilizes rigid mobility elements in the scye (i.e., shoulder) and the upper arm regions. The suit architecture also utilizes rigid thigh disconnect elements to create a quick disconnect approximately located above the knee. This feature allows commonality of the lower portion of the suit (from the thigh disconnect down), making the lower legs common across two suit configurations. This suit must interface with the Orion vehicle seat subsystem, which includes seat components, lateral supports, and restraints. Due to the unique configuration of spacesuit mobility elements, combined with the need to provide occupant protection during dynamic vehicle events, risks have been identified with potential injury due to the suit characteristics described above. To address the risk concerns, a test series has been developed in coordination with the Injury Biomechanics Research Laboratory [IBRL] to evaluate the likelihood and consequences of these potential issues. Testing includes use of Anthropomorphic Test Devices [ATDs; vernacularly referred to as "crash test dummies"], Post Mortem Human Subjects [PMHS], and representative seat/suit hardware in combination with high linear acceleration events. The ensuing treatment focuses on test purpose and objectives; test hardware, facility, and setup; and preliminary results.

  14. Endocannabinoid dynamics gate spike-timing dependent depression and potentiation

    PubMed Central

    Cui, Yihui; Prokin, Ilya; Xu, Hao; Delord, Bruno; Genet, Stephane; Venance, Laurent; Berry, Hugues

    2016-01-01

    Synaptic plasticity is a cardinal cellular mechanism for learning and memory. The endocannabinoid (eCB) system has emerged as a pivotal pathway for synaptic plasticity because of its widely characterized ability to depress synaptic transmission on short- and long-term scales. Recent reports indicate that eCBs also mediate potentiation of the synapse. However, it is not known how eCB signaling may support bidirectionality. Here, we combined electrophysiology experiments with mathematical modeling to question the mechanisms of eCB bidirectionality in spike-timing dependent plasticity (STDP) at corticostriatal synapses. We demonstrate that STDP outcome is controlled by eCB levels and dynamics: prolonged and moderate levels of eCB lead to eCB-mediated long-term depression (eCB-tLTD) while short and large eCB transients produce eCB-mediated long-term potentiation (eCB-tLTP). Moreover, we show that eCB-tLTD requires active calcineurin whereas eCB-tLTP necessitates the activity of presynaptic PKA. Therefore, just like glutamate or GABA, eCB form a bidirectional system to encode learning and memory. DOI: http://dx.doi.org/10.7554/eLife.13185.001 PMID:26920222

  15. Relationship between force-time and velocity-time characteristics of dynamic and isometric muscle actions.

    PubMed

    Khamoui, Andy V; Brown, Lee E; Nguyen, Diamond; Uribe, Brandon P; Coburn, Jared W; Noffal, Guillermo J; Tran, Tai

    2011-01-01

    Previous research has investigated the force-time curve characteristics of isometric and dynamic muscle actions; however, few studies have addressed their relationship to dynamic exercise velocity-time variables. The purpose of this study was to investigate relationships between velocity-time characteristics (high pull and vertical jump peak velocity and rate of velocity development [HPPV, HPRVD, VJPV, VJRVD]), force-time characteristics (isometric peak force [IsoPF], body mass adjusted isometric peak force [IsoPF/BM], isometric rate of force development at different millisecond windows [IsoRFD50-250], dynamic peak force [HPPF], body mass adjusted dynamic peak force [HPPF/BM]), and vertical jump height (VJHeight). Nineteen recreationally trained men (age 23.89 ± 2.92 yr; height 176.32 ± 7.06 cm; mass 78.76 ± 16.50 kg) completed 2 testing sessions. The first session consisted of 3 isometric mid-thigh pulls on a force plate with each repetition held for 3 seconds. On the second testing session, subjects completed 3 dynamic mid-thigh high pulls with 30% IsoPF followed by 3 vertical jumps on a force plate. The HPRVD correlated with IsoRFD50 (r = 0.52) and IsoRFD100 (r = 0.49). The HPPV correlated with IsoPF/BM (r = -0.60), IsoRFD50 (r = 0.56), and IsoRFD100 (r = 0.56). The VJHeight correlated with IsoPF/BM (r = 0.61), whereas VJPV correlated with IsoPF/BM (r = 0.62). These correlations suggest that explosive isometric force production within 50 to 100 milliseconds may influence the ability to accelerate an implement or body and attain high velocity, albeit in a moderate fashion. In addition, body mass adjusted strength may positively influence vertical jump parameters.

  16. Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons.

    PubMed

    Lien, Cheng-Chang; Jonas, Peter

    2003-03-15

    Kv3 channels are thought to be essential for the fast-spiking (FS) phenotype in GABAergic interneurons, but how these channels confer the ability to generate action potentials (APs) at high frequency is unknown. To address this question, we developed a fast dynamic-clamp system (approximately 50 kHz) that allowed us to add a Kv3 model conductance to CA1 oriens alveus (OA) interneurons in hippocampal slices. Selective pharmacological block of Kv3 channels by 0.3 mm 4-aminopyridine or 1 mm tetraethylammonium ions led to a marked broadening of APs during trains of short stimuli and a reduction in AP frequency during 1 sec stimuli. The addition of artificial Kv3 conductance restored the original AP pattern. Subtraction of Kv3 conductance by dynamic clamp mimicked the effects of the blockers. Application of artificial Kv3 conductance also led to FS in OA interneurons after complete K+ channel block and even induced FS in hippocampal pyramidal neurons in the absence of blockers. Adding artificial Kv3 conductance with altered deactivation kinetics revealed a nonmonotonic relationship between mean AP frequency and deactivation rate, with a maximum slightly above the original value. Insertion of artificial Kv3 conductance with either lowered activation threshold or inactivation also led to a reduction in the mean AP frequency. However, the mechanisms were distinct. Shifting the activation threshold induced adaptation, whereas adding inactivation caused frequency-dependent AP broadening. In conclusion, Kv3 channels are necessary for the FS phenotype of OA interneurons, and several of their gating properties appear to be optimized for high-frequency repetitive activity.

  17. Calcium‐activated chloride current determines action potential morphology during calcium alternans in atrial myocytes

    PubMed Central

    Kanaporis, Giedrius

    2016-01-01

    Key points Cardiac alternans – periodic beat‐to‐beat alternations in contraction, action potential (AP) morphology or cytosolic calcium transient (CaT) amplitude – is a high risk indicator for cardiac arrhythmias and sudden cardiac death. However, it remains an unresolved issue whether beat‐to‐beat alternations in intracellular Ca2+ ([Ca2+]i) or AP morphology are the primary cause of pro‐arrhythmic alternans.Here we show that in atria AP alternans occurs secondary to CaT alternans.CaT alternans leads to complex beat‐to‐beat changes in Ca2+‐regulated ion currents that determine alternans of AP morphology.We report the novel finding that alternans of AP morphology is largely sustained by the activity of Ca2+‐activated Cl− channels (CaCCs). Suppression of the CaCCs significantly reduces AP alternans, while CaT alternans remains unaffected.The demonstration of a major role of CaCCs in the development of AP alternans opens new possibilities for atrial alternans and arrhythmia prevention. Abstract Cardiac alternans, described as periodic beat‐to‐beat alternations in contraction, action potential (AP) morphology or cytosolic Ca transient (CaT) amplitude, is a high risk indicator for cardiac arrhythmias and sudden cardiac death. We investigated mechanisms of cardiac alternans in single rabbit atrial myocytes. CaTs were monitored simultaneously with membrane currents or APs recorded with the patch clamp technique. Beat‐to‐beat alternations of AP morphology and CaT amplitude revealed a strong quantitative correlation. Application of voltage clamp protocols in the form of pre‐recorded APs (AP‐clamp) during pacing‐induced CaT alternans revealed a Ca2+‐dependent current consisting of a large outward component (4.78 ± 0.58 pA pF–1 in amplitude) coinciding with AP phases 1 and 2 that was followed by an inward current (−0.42 ± 0.03 pA pF–1; n = 21) during AP repolarization. Approximately 90% of the initial outward current

  18. Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

    PubMed Central

    Grewe, Benjamin F.; Bonnan, Audrey; Frick, Andreas

    2009-01-01

    Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location. PMID:20508744

  19. Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

    PubMed Central

    Gasser, R N; Vaughan-Jones, R D

    1990-01-01

    1. Ischaemia was simulated in the isolated sheep cardiac Purkinje fibre and guinea-pig papillary muscle by immersing the preparations in paraffin oil. Ion-selective microelectrodes recorded potassium (Ks+) and pH (pHs) in the thin film of Tyrode solution trapped at the fibre surface while other microelectrodes recorded intracellular pH (pHi), membrane potential and action potentials (AP) (evoked by field stimulation), or membrane current (two-microelectrode voltage clamp in shortened Purkinje fibres). Twitch tension was also monitored. The paraffin oil model reproduced the salient characteristics of myocardial ischaemia, i.e. a decrease of twitch tension; a decrease of pHi and pHs; a rise in Ks+ (by 2-3 mM); a depolarization of diastolic membrane potential; considerable shortening of the AP (up to 30% within 4 min). 2. The sulphonylurea compounds, glibenclamide (200 microM) and tolbutamide (1 mM), known inhibitors of the KATP channel, completely blocked the ischaemic rise of Ks+ and prevented AP shortening. Ischaemic tension decline was notably less pronounced in the presence of sulphonylureas. 3. The ischaemic increase of slope conductance (Purkinje fibre) was prevented by 1 mM-tolbutamide and 200 microM-glibenclamide. 4. Sulphonylureas did not affect resting membrane potential, the AP or the current-voltage relationship under non-ischaemic conditions (this also indicates that ischaemic Ks+ accumulation is not fuelled by the background K+ current [iK1] which was shown, as expected, to be Ba2+ sensitive). 5. In a normally perfused preparation, reducing intracellular ATP by inhibiting glycolysis with 2-deoxyglucose (DOG) produced a similar AP shortening plus a membrane hyperpolarization, both of which were inhibited by tolbutamide or glibenclamide. The AP shortening was not related uniquely to the fall of pHi observed under these conditions since experimentally reducing pHi (by reducing pHo in the absence of DOG) lengthened rather than shortened the AP. 6. The

  20. Characterization of action potential-evoked calcium transients in mouse postganglionic sympathetic axon bundles.

    PubMed

    Jackson, V M; Trout, S J; Brain, K L; Cunnane, T C

    2001-11-15

    1. Action potential-evoked Ca(2+) transients in postganglionic sympathetic axon bundles in mouse vas deferens have been characterized using confocal microscopy and Ca(2+) imaging. 2. Axonal Ca(2+) transients were tetrodotoxin sensitive. The amplitude depended on both the frequency of stimulation and the number of stimuli in a train. 3. Removal of extracellular Ca(2+) abolished the Ca(2+) transient. Cd(2+)(100 microM) inhibited the Ca(2+) transient by 78 +/- 10 %. The N-type Ca(2+) channel blocker omega-conotoxin GVIA (0.1 microM) reduced the amplitude by -35 +/-4 %, whereas nifedipine (10 microM; L-type) and omega-conotoxin MVIIC (0.1 microM; P/Q type) were ineffective. 4. Caffeine (10 mM), ryanodine (10 microM), cyclopiazonic acid (30 microM) or CCCP (10 microM) had no detectable effects. 5. Blockade of large and small conductance Ca(2+)-dependent K+ channels with iberiotoxin (0.1 microM) and apamin (1 microM), respectively, or Ca(2+)-dependent Cl(-) channels by niflumic acid (100 microM) did not alter Ca(2+) transients. 6. In contrast, the non-specific K+ channel blockers tetraethylammonium (10 mM) and 4-aminopyridine (10 mM) markedly increased the amplitude of the Ca(2+) transient. Blockade of delayed rectifiers and A-like K+ channels, by tityustoxin-K (alpha) (0.1 microM) and pandinustoxin-K (alpha) (10 nM), respectively, also increased the Ca(2+) transient amplitude. 7. Thus, Ca(2+) transients are evoked by Na(+)-dependent action potentials in axons. These transients originate mainly from Ca(2+) entry through voltage-dependent Ca(2+) channels (80 % Cd(2+) sensitive of which 40 % was attributable to N-type). Twenty per cent of the Ca(2+) transient was not due to Ca(2+) entry through voltage-gated Ca(2+) channels. Intracellular stores and mitochondria were not involved in the generation of the transient. Ca(2+) transients are modulated by A-like K+ channels and delayed rectifiers (possibly K(V)1.2) but not by Ca(2+)-activated ion channels.

  1. Actions of the digitalis analogue strophanthidin on action potentials and L-type calcium current in single cells isolated from the rabbit atrioventricular node.

    PubMed Central

    Hancox, J. C.; Levi, A. J.

    1996-01-01

    1. The atrioventricular node (AVN) of the heart is vital to normal cardiac function and is a major site of antiarrhythmic drug action. This study describes the effects of the cardiac glycoside analogue strophanthidin on spontaneous action potentials and L-type calcium current recorded from single AVN cells isolated from the rabbit heart. 2. With a standard KCl-based internal dialysis solution, exposure to 50 microM strophanthidin produced a progressive depolarization of the maximum diastolic potential and a reduction in action potential amplitude and upstroke velocity. Sustained application resulted in the loss of action potentials and occurrence of spontaneous 'bell-shaped' depolarizations. 3. Cells were whole-cell voltage clamped at -40 mV and depolarizing voltage clamps applied. With a standard KCl-based internal dialysis solution, exposure to 50 microM strophanthidin caused a large reduction of ICa,L at all potentials between -30 and +40 mV (n = 4). At + 10 mV, the mean ICa,L amplitude was reduced from -232 +/- 65 pA to -48 +/- 26 pA (P < 0.05; 1 test; n = 5 cells). 4. To record ICa,L more selectively, cells were dialysed with a Cs-based pipette solution. A short strophanthidin exposure reduced ICa,L amplitude from -250 +/- 31 pA to -88 +/- 19 pA (P < 0.001; n = 8 cells). For both KCl and CsCl-based solutions it was observed that sustained exposure to strophanthidin for several minutes caused spontaneous inward fluctuations in the membrane current record similar to the 'ITI' (arrhythmogenic oscillatory transient inward) current shown for other cardiac cells. 5. When the calcium chelator BAPTA was added to the pipette solution (10 mM), the reduction in ICa,L by strophanthidin was largely eliminated (P > 0.1), and no spontaneous inward current fluctuations were observed after sustained exposure to strophanthidin (n = 8 cells). 6. When external Ca in the perfusate was replaced with Ba, strophanthidin did not significantly reduce the Ba current through L

  2. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.

    PubMed

    Storm, J F

    1987-04-01

    1. The repolarization of the action potential, and a fast after-hyperpolarization (a.h.p.) were studied in CA1 pyramidal cells (n = 76) in rat hippocampal slices (28-37 degrees C). Single spikes were elicited by brief (1-3 ms) current pulses, at membrane potentials close to rest (-60 to -70 mV). 2. Each action potential was followed by four after-potentials: (a) the fast a.h.p., lasting 2-5 ms; (b) an after-depolarization; (c) a medium a.h.p., (50-100 ms); and (d) a slow a.h.p. (1-2 s). Both the fast a.h.p. and the slow a.h.p. (but not the medium a.h.p.) were inhibited by Ca2+-free medium or Ca2+-channel blockers (Co2+, Mn2+ or Cd2+); but tetraethylammonium (TEA; 0.5-2 nM) blocked only the fast a.h.p., and noradrenaline (2-5 microM) only the slow a.h.p. This suggests that two Ca2+-activated K+ currents were involved: a fast, TEA-sensitive one (IC) underlying the fast a.h.p., and a slow noradrenaline-sensitive one (IAHP) underlying the slow a.h.p. 3. Like the fast a.h.p., spike repolarization seems to depend on a Ca2+-dependent K+ current of the fast, TEA-sensitive kind (IC). The repolarization was slowed by Ca2+-free medium, Co2+, Mn2+, Cd2+, or TEA, but not by noradrenaline. Charybdotoxin (CTX; 30 nM), a scorpion toxin which blocks the large-conductance Ca2+-activated K+ channel in muscle, had a similar effect to TEA. The effects of TEA and Cd2+ (or Mn2+) showed mutual occlusion. Raising the external K+ concentration reduced the fast a.h.p. and slowed the spike repolarization, whereas Cl- loading of the cell was ineffective. 4. The transient K+ current, IA, seems also to contribute to spike repolarization, because: (a) 4-aminopyridine (4-AP; 0.1 mM), which blocks IA, slowed the spike repolarization; (b) depolarizing pre-pulses, which inactivate IA, had a similar effect; (c) hyperpolarizing pre-pulses speeded up the spike repolarization; (d) the effects of 4-AP and pre-pulses persisted during Ca2+ blockade (like IA); and (e) depolarizing pre-pulses reduced the

  3. Water savings potentials of irrigation systems: dynamic global simulation

    NASA Astrophysics Data System (ADS)

    Jägermeyr, J.; Gerten, D.; Heinke, J.; Schaphoff, S.; Kummu, M.; Lucht, W.

    2015-04-01

    Global agricultural production is heavily sustained by irrigation, but irrigation system efficiencies are often surprisingly low. However, our knowledge of irrigation efficiencies is mostly confined to rough indicative estimates for countries or regions that do not account for spatio-temporal heterogeneity due to climate and other biophysical dependencies. To allow for refined estimates of global agricultural water use, and of water saving and water productivity potentials constrained by biophysical processes and also non-trivial downstream effects, we incorporated a dynamic representation of the three major irrigation systems (surface, sprinkler, and drip) into a process-based bio- and agrosphere model, LPJmL. Based on this enhanced model we provide a gridded worldmap of dynamically retrieved irrigation efficiencies reflecting differences in system types, crop types, climatic and hydrologic conditions, and overall crop management. We find pronounced regional patterns in beneficial irrigation efficiency (a refined irrigation efficiency indicator accounting for crop-productive water consumption only), due to differences in these features, with lowest values (< 30%) in South Asia and Sub-Saharan Africa and highest values (> 60%) in Europe and North America. We arrive at an estimate of global irrigation water withdrawal of 2396 km3 (2004-2009 average); irrigation water consumption is calculated to be 1212 km3, of which 511 km3 are non-beneficially consumed, i.e. lost through evaporation, interception, and conveyance. Replacing surface systems by sprinkler or drip systems could, on average across the world's river basins, reduce the non-beneficial consumption at river basin level by 54 and 76%, respectively, while maintaining the current level of crop yields. Accordingly, crop water productivity would increase by 9 and 15%, respectively, and by much more in specific regions such as in the Indus basin. This study significantly advances the global quantification of

  4. Motor Unit Number Estimation and Motor Unit Action Potential Analysis in Carpal Tunnel Syndrome

    PubMed Central

    Sohn, Min Kyun; Jee, Sung Ju; Kim, Young-Jae; Shin, Hyun-Dae

    2011-01-01

    Objective To evaluate the clinical significance of motor unit number estimation (MUNE) and quantitative analysis of motor unit action potential (MUAP) in carpal tunnel syndrome (CTS) according to electrophysiologic severity, ultrasonographic measurement and clinical symptoms. Method We evaluated 78 wrists of 45 patients, who had been diagnosed with CTS and 42 wrists of 21 healthy controls. Median nerve conduction studies, amplitude and duration of MUAP, and the MUNE of the abductor pollicis brevis were measured. The cross sectional area (CSA) of the median nerve at the pisiform and distal radioulnar joint level was determined by high resolution ultrasonography. Clinical symptom of CTS was assessed using the Boston Carpal Tunnel Questionnaire (BCTQ). Results The MUNE, the amplitude and the duration of MUAP of the CTS group were significantly different from those found in the control group. The area under the ROC curve was 0.944 for MUNE, 0.923 for MUAP amplitude and 0.953 for MUAP duration. MUNE had a negative correlation with electrophysiologic stage of CTS, amplitude and duration of MUAP, CSA at pisiform level, and the score of BCTQ. The amplitude and duration of MUAP had a positive correlation with the score of BCTQ. The electrophysiologic stage was correlated with amplitude but not with the duration of MUAP. Conclusion MUNE, amplitude and duration of MUAP are useful tests for diagnosis of CTS. In addition, the MUNE serves as a good indicator of CTS severity. PMID:22506210

  5. Adhesion to Carbon Nanotube Conductive Scaffolds Forces Action-Potential Appearance in Immature Rat Spinal Neurons

    PubMed Central

    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. PMID:23951361

  6. The central action of salbutamol, a beta-agonist with a potential antidepressant activity.

    PubMed

    Przegalinski, E; Baran, L; Kedrek, G

    1980-01-01

    The pharmacological profile of salbutamol, an agonist of beta-adrenergic receptors and a potential antidepressant drug, and its effect on the central serotonin system were studied. It was found that salbutamol either had no effect, or, at higher doses, inhibited the spontaneous activity of mice and rats; it did not influence significantly either the produced by amphetamine locomotor stimulation (in mice and rats) or amphetamine stereotype (in rats). Salbutamol while not affecting body temperature of normal mice reversed hypothermia but not ptosis induced by reserpine, and counteracted the hypothermic action of apomorphine in mice. It neither affected the spiperone-induced catalepsy nor was active in the behavioural despair test in rats. Salbutamol had no effect either, on the fenfluramine-induced hyperthermia in rabbits, on the 5-hydroxytryptophan-induced head twitch reaction in mice, on the tryptamine-induced clonic convulsions of forepaw in rats on the flexor reflex in spinal rats, or on the quipazine- or fenfluramine-induced stimulation of this reflex. The above findings indicate that the pharmacological profile of salbutamol resembles that of classical imipramine-like antidepressant drugs to a very small extent and it does not affect the central serotonergic transmission.

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

    PubMed

    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.

  8. Effects of stochastic channel gating and distribution on the cardiac action potential.

    PubMed

    Lemay, Mathieu; de Lange, Enno; Kucera, Jan P

    2011-07-21

    Ion channels exhibit stochastic conformational changes determining their gating behavior. In addition, the process of protein turnover leads to a natural variability of the number of membrane and gap junctional channels. Nevertheless, in computational models, these two aspects are scarcely considered and their impacts are largely unknown. We investigated the effects of stochastic current fluctuations and channel distributions on action potential duration (APD), intercellular conduction delays (ICDs) and conduction blocks using a modified ventricular cell model (Rudy et al.) with Markovian formulations of the principal ion currents (to simulate their stochastic open-close gating behavior) and with channel counts drawn from Poisson distributions (to simulate their natural variability). In single cells, APD variability (coefficient of variation: 1.6% at BCL=1000ms) was essentially caused by stochastic channel gating of I(Ks), persistent I(Na) and I(Ca,L). In cell strands, ICD variability induced by stochastic channel gating and Poissonian channel distributions was low under normal conditions. Nonetheless, at low intercellular coupling levels, Poissonian gap junctional channel distribution resulted in a large ICD variability (coefficient of variation >20%), highly heterogeneous conduction patterns and conduction blocks. Therefore, the stochastic behavior of current fluctuations and channel distributions can contribute to the heterogeneity of conduction patterns and to conduction block, as observed previously in experiments in cardiac tissue with altered intercellular coupling.

  9. Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization.

    PubMed

    Labro, Alain J; Priest, Michael F; Lacroix, Jérôme J; Snyders, Dirk J; Bezanilla, Francisco

    2015-12-17

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission.

  10. Direction-Selective Circuitry in Rat Retina Develops Independently of GABAergic, Cholinergic and Action Potential Activity

    PubMed Central

    He, Shigang

    2011-01-01

    The ON-OFF direction selective ganglion cells (DSGCs) in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience. PMID:21573161

  11. Motor unit action potential conduction velocity estimated from surface electromyographic signals using image processing techniques.

    PubMed

    Soares, Fabiano Araujo; Carvalho, João Luiz Azevedo; Miosso, Cristiano Jacques; de Andrade, Marcelino Monteiro; da Rocha, Adson Ferreira

    2015-09-17

    In surface electromyography (surface EMG, or S-EMG), conduction velocity (CV) refers to the velocity at which the motor unit action potentials (MUAPs) propagate along the muscle fibers, during contractions. The CV is related to the type and diameter of the muscle fibers, ion concentration, pH, and firing rate of the motor units (MUs). The CV can be used in the evaluation of contractile properties of MUs, and of muscle fatigue. The most popular methods for CV estimation are those based on maximum likelihood estimation (MLE). This work proposes an algorithm for estimating CV from S-EMG signals, using digital image processing techniques. The proposed approach is demonstrated and evaluated, using both simulated and experimentally-acquired multichannel S-EMG signals. We show that the proposed algorithm is as precise and accurate as the MLE method in typical conditions of noise and CV. The proposed method is not susceptible to errors associated with MUAP propagation direction or inadequate initialization parameters, which are common with the MLE algorithm. Image processing -based approaches may be useful in S-EMG analysis to extract different physiological parameters from multichannel S-EMG signals. Other new methods based on image processing could also be developed to help solving other tasks in EMG analysis, such as estimation of the CV for individual MUs, localization and tracking of innervation zones, and study of MU recruitment strategies.

  12. 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

  13. 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.

  14. Telemetry system for reliable recording of action potentials from freely moving rats.

    PubMed

    Hawley, Emerson S; Hargreaves, Eric L; Kubie, John L; Rivard, Bruno; Muller, Robert U

    2002-01-01

    Recording single cells from alert rats currently requires a cable to connect brain electrodes to the acquisition system. If no cable were necessary, a variety of interesting experiments would become possible, and the design of other experiments would be simplified. To eliminate the need for a cable we have developed a one-channel radiotelemetry system that is easily carried by a rat. This system transmits a signal that is reliable, highly accurate and can be detected over distances of > or = 20 m. The mobile part of the system has three components: (1) a headstage with built-in amplifiers that plugs into the connector for the electrode array on the rat's head; the headstage also incorporates a light-emitting diode (LED) used to track the rat's position; (2) a backpack that contains the transmitter and batteries (2 N cells); the backpack also provides additional amplification of the single cell signals; and (3) a short cable that connects the headstage to the backpack; the cable supplies power to the headstage amplifiers and the LED, and carries the physiological signals from the headstage to the backpack. By using a differential amplifier and recording between two brain microelectrodes the system can transmit action potential activity from two nearly independent sources. In a future improvement, two transmitters with different frequencies would be used telemeter signals from four microelectrodes simultaneously.

  15. Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons

    PubMed Central

    Hamada, Mustafa S.; Popovic, Marko A.; Kole, Maarten H. P.

    2017-01-01

    In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex. PMID:28289377

  16. Sensitivity analysis of potential events affecting the double-shell tank system and fallback actions

    SciTech Connect

    Knutson, B.J.

    1996-09-27

    Sensitivity analyses were performed for fall-back positions (i.e., management actions) to accommodate potential off-normal and programmatic change events overlaid on the waste volume projections and their uncertainties. These sensitivity analyses allowed determining and ranking tank system high-risk parameters and fall- back positions that will accommodate the respective impacts. This quantification of tank system impacts shows periods where tank capacity is sensitive to certain variables that must be carefully managed and/or evaluated. Identifying these sensitive variables and quantifying their impact will allow decision makers to prepare fall-back positions and focus available resources on the highest impact parameters where technical data are needed to reduce waste projection uncertainties. For noncomplexed waste, the period of capacity vulnerability occurs during the years of single-shell tank (SST) retrieval (after approximately 2009) due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate and 200-East SST solids transfer volume. For complexed waste, the period of capacity vulnerability occurs during the period after approximately 2005 due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate. 200-East SST solids transfer volume. complexed waste reduction factor using evaporation, and 200-west saltwell liquid porosity.

  17. A regenerative microchannel device for recording multiple single-unit action potentials in awake, ambulatory animals.

    PubMed

    Srinivasan, Akhil; Tipton, John; Tahilramani, Mayank; Kharbouch, Adel; Gaupp, Eric; Song, Chao; Venkataraman, Poornima; Falcone, Jessica; Lacour, Stéphanie P; Stanley, Garrett B; English, Arthur W; Bellamkonda, Ravi V

    2016-02-01

    Despite significant advances in robotics, commercially advanced prosthetics provide only a small fraction of the functionality of the amputated limb that they are meant to replace. Peripheral nerve interfacing could provide a rich controlling link between the body and these advanced prosthetics in order to increase their overall utility. Here, we report on the development of a fully integrated regenerative microchannel interface with 30 microelectrodes and signal extraction capabilities enabling evaluation in an awake and ambulatory rat animal model. In vitro functional testing validated the capability of the microelectrodes to record neural signals similar in size and nature to those that occur in vivo. In vitro dorsal root ganglia cultures revealed striking cytocompatibility of the microchannel interface. Finally, in vivo, the microchannel interface was successfully used to record a multitude of single-unit action potentials through 63% of the integrated microelectrodes at the early time point of 3 weeks. This marks a significant advance in microchannel interfacing, demonstrating the capability of microchannels to be used for peripheral nerve interfacing.

  18. Effects of aminoglycoside antibiotics on calcium action potentials and calcium channel currents.

    PubMed

    Suarez-Kurtz, G

    1989-01-01

    The author reviews work from his laboratory on the effects of neomycin and streptomycin on the Ca(2+)-dependent electrogenesis of crustacean muscle fibers and on two distinct Ca2+ channel currents of pituitary cells. The data indicate that these aminoglycosides inhibit the graded electrogenesis and the action potentials of crustacean muscle; these effects are accompanied by inhibition of tension development upon membrane depolarization. Increasing the extracellular Ca2+ concentration reverses the aminoglycoside-induced blockade of the Ca(2+)-dependent electrogenesis of the muscle fibers. Neomycin blocked both the transient (T-type) and the slowly-inactivating (L-type) Ca2+ currents of clonal pituitary GH3 cells, studied with the whole cell modality of the patch clamp technique. The blockade of these currents was not modulated by activation or inactivation of the channels. Neomycin inhibited also the currents conveyed by Na+ through the slowly-inactivating Ca2+ in cells equilibrated with Ca(2+)-free media. Interpretation of these data led to the suggestion that the blockade of Ca2+ currents by neomycin (and other aminoglycosides) cannot be explained by competition with Ca2+ ions for binding to high affinity transition sites within the Ca2+ channel path.

  19. Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

    PubMed Central

    Hamada, Mustafa S.; Goethals, Sarah; de Vries, Sharon I.; Brette, Romain

    2016-01-01

    In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies. PMID:27930291

  20. Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model.

    PubMed

    Courtemanche, M; Ramirez, R J; Nattel, S

    1998-07-01

    The mechanisms underlying many important properties of the human atrial action potential (AP) are poorly understood. Using specific formulations of the K+, Na+, and Ca2+ currents based on data recorded from human atrial myocytes, along with representations of pump, exchange, and background currents, we developed a mathematical model of the AP. The model AP resembles APs recorded from human atrial samples and responds to rate changes, L-type Ca2+ current blockade, Na+/Ca2+ exchanger inhibition, and variations in transient outward current amplitude in a fashion similar to experimental recordings. Rate-dependent adaptation of AP duration, an important determinant of susceptibility to atrial fibrillation, was attributable to incomplete L-type Ca2+ current recovery from inactivation and incomplete delayed rectifier current deactivation at rapid rates. Experimental observations of variable AP morphology could be accounted for by changes in transient outward current density, as suggested experimentally. We conclude that this mathematical model of the human atrial AP reproduces a variety of observed AP behaviors and provides insights into the mechanisms of clinically important AP properties.

  1. Quantitative weight of evidence to assess confidence in potential modes of action.

    PubMed

    Becker, Richard A; Dellarco, Vicki; Seed, Jennifer; Kronenberg, Joel M; Meek, Bette; Foreman, Jennifer; Palermo, Christine; Kirman, Chris; Linkov, Igor; Schoeny, Rita; Dourson, Michael; Pottenger, Lynn H; Manibusan, Mary K

    2017-02-20

    The evolved World Health Organization/International Programme on Chemical Safety mode of action (MOA) framework provides a structure for evaluating evidence in pathways of causally linked key events (KE) leading to adverse health effects. Although employed globally, variability in use of the MOA framework has led to different interpretations of the sufficiency of evidence in support of hypothesized MOAs. A proof of concept extension of the MOA framework is proposed for scoring confidence in the supporting data to improve scientific justification for MOA use in characterizing hazards and selecting dose-response extrapolation methods for specific chemicals. This involves selecting hypothesized MOAs, and then, for each MOA, scoring the weight of evidence (WOE) in support of causality for each KE using evolved Bradford Hill causal considerations (biological plausibility, essentiality, dose-response concordance, consistency, and analogy). This early proof of concept method is demonstrated by comparing two potential MOAs (mutagenicity and peroxisome proliferator activated receptor-alpha) for clofibrate, a rodent liver carcinogen. Quantitative confidence scoring of hypothesized MOAs is shown to be useful in characterizing the likely operative MOA. To guide method refinement and future confidence scoring for a spectrum of MOAs, areas warranting further focus and lessons learned, including the need to incorporate a narrative discussion of the weights used in the evaluation and an overall evaluation of the plausibility of the outcome, are presented.

  2. Effects of terpineol on the compound action potential of the rat sciatic nerve.

    PubMed

    Moreira, M R; Cruz, G M; Lopes, M S; Albuquerque, A A; Leal-Cardoso, J H

    2001-10-01

    Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the perfumery industry. It is an important chemical constituent of the essential oil of many plants with widespread applications in folk medicine and in aromatherapy. The effects of terpineol on the compound action potential (CAP) of rat sciatic nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At 100 microM, terpineol had no demonstrable effect. At 300 microM terpineol, peak-to-peak amplitude and conduction velocity of CAP were significantly reduced at the end of 180-min exposure of the nerve to the drug, from 3.28 +/- 0.22 mV and 33.5 +/- 7.05 m/s, respectively, to 1.91 +/- 0.51 mV and 26.2 +/- 4.55 m/s. At 600 microM, terpineol significantly reduced peak-to-peak amplitude and conduction velocity from 2.97 +/- 0.55 mV and 32.8 +/- 3.91 m/s to 0.24 +/- 0.23 mV and 2.72 +/- 2.72 m/s, respectively (N = 5). All these effects developed slowly and were reversible upon 180-min washout.

  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. Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.

    PubMed Central

    van der Velden, V H

    1998-01-01

    GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized. PMID:9792333

  5. The influence of passband limitation on the waveform of extracellular action potential.

    PubMed

    Mizuhiki, Takashi; Inaba, Kiyonori; Setogawa, Tsuyoshi; Toda, Koji; Ozaki, Shigeru; Shidara, Muneteka

    2012-03-01

    The duration of the extracellular action potential (EAP) in single neuronal recording has often been used as a clue to infer biochemical, physiological or functional substrate of the recorded neurons, e.g. neurochemical type. However, when recording a neuronal activity, the high-pass filter is routinely used to achieve higher signal-to-noise ratio. Signal processing theory predicts that passband limitation stretches the waveform of discrete brief impulse. To examine whether the duration of filtered EAP could be the reliable measure, we investigated the influence of high-pass filter both by simulation and unfiltered unit recording data from monkey dorsal raphe. Consistent with the findings in recent theoretical study, the unfiltered EAPs displayed the sharp wave without following bumps. The duration of unfiltered EAP was not correlated with that of filtered EAP. Thus the duration of original EAP cannot be estimated from filtered EAP. It is needed to reexamine the EAP duration measured for classifying the neurons whose activities were recorded under the passband limitation in the related studies.

  6. 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

  7. Modulation of action potential trains in rabbit saphenous nerve unmyelinated fibers.

    PubMed

    Zhu, Zhi-Ru; Liu, Yi-Hui; Ji, Wei-Gang; Duan, Jian-Hong; Hu, San-Jue

    2013-01-01

    Usually, the main axon is assumed to faithfully conduct action potentials (APs). Recent data have indicated that neural processing can occur along the axonal path. However, the patterns and mechanisms of temporal coding are not clear. In the present study, single fiber recording was used to analyze activity-dependent modulation of AP trains in the main axons of C fibers in the rabbit saphenous nerve. Trains of 5 superthreshold electrical pulses at interstimulus intervals of 20 or 50 ms were applied to the nerve trunk for 200 s. The interspike intervals (ISIs) for these trains were compared to the input interstimulus intervals. Three basic types of C fibers were observed in response to repeated stimuli: first, the ISI between the first and second AP (ISI1-2) of type 1 was longer than the interstimulus interval; second, the ISI1-2 of type 2 showed wavelike fluctuations around the interstimulus interval, and third, the ISI1-2 of type 3 exhibited shorter intervals for a long period. Furthermore, both 4-aminopyridine-sensitive potassium and hyperpolarization-activated cation currents were involved in the modulation of ISI1-2 of train pulses. These data provide new evidence that multiple modes of neural conduction can occur along the main axons of C fibers.

  8. Kv3.1 uses a timely resurgent K+ current to secure action potential repolarization

    PubMed Central

    Labro, Alain J.; Priest, Michael F.; Lacroix, Jérôme J.; Snyders, Dirk J.; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K+ currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na+ and K+ currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3–S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  9. 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

    2016-02-08

    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.

  10. 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

  11. Effect of rapid delayed rectifier current on hysteresis in restitution of action potential duration in swine.

    PubMed

    Agarwal, Anuj; Jing, Linyuan; Patwardhan, Abhijit

    2012-01-01

    Electrical stability in the heart depends on two important factors; restitution of action potential duration (APD) and memory. Repolarization currents play an important role in determining APD and also affect memory. We determined the effects of blocking the rapid component of the delayed rectifier (I(Kr)) on a quantifiable measure of memory, i.e. hysteresis in restitution of APD, in swine. Transmembrane potentials were recorded from right ventricular endocardial tissues. Two pacing protocols with explicit control of diastolic interval (DI) were used to change DIs in a sequential and sinusoidal pattern to quantify hysteresis in restitution of APD. E-4031 (5 µM/L) was used to block I(Kr). Measures of memory and restitution were quantified by calculating hysteresis loop thickness, area, overall tilt, and maximum and minimum delays between DIs and APDs. Blocking I(Kr) with E-4031 increased the baseline APD, loop thickness, area, and tilt (p<0.05). However, loop thickness did not increase beyond what could be predicted by the increase in baseline APD after block of I(Kr). The substantial change in APD after blocking I(Kr) suggests that this current plays a major role in repolarization in the swine. Loop thickness is a measure of memory, an increase in which is predicted by theory to reduce instability in activation. In our study, the substantial increase in loop thickness could be accounted for by an equally substantial increase in APD and therefore does not necessarily indicate increased memory after blocking I(Kr). Our results also suggest that factors based on restitution and memory need to be considered in the context of operating point, i.e. baseline APD, when they are used to explore mechanisms that affect electrical stability in the heart.

  12. Effect of thermal acclimation on action potentials and sarcolemmal K+ channels from Pacific bluefin tuna cardiomyocytes.

    PubMed

    Galli, G L J; Lipnick, M S; Block, B A

    2009-08-01

    To sustain cardiac muscle contractility relatively independent of temperature, some fish species are capable of temporarily altering excitation-contraction coupling processes to meet the demands of their environment. The Pacific bluefin tuna, Thunnus orientalis, is a partially endothermic fish that inhabits a wide range of thermal niches. The present study examined the effects of temperature and thermal acclimation on sarcolemmal K(+) currents and their role in action potential (AP) generation in bluefin tuna cardiomyocytes. Atrial and ventricular myocytes were enzymatically isolated from cold (14 degrees C)- and warm (24 degrees C)-acclimated bluefin tuna. APs and current-voltage relations of K(+) channels were measured using the whole cell current and voltage clamp techniques, respectively. Data were collected either at the cardiomyocytes' respective acclimation temperature of 14 or 24 degrees C or at a common test temperature of 19 degrees C (to reveal the effects of acclimation). AP duration (APD) was prolonged in cold-acclimated (CA) cardiomyocytes tested at 14 degrees C compared with 19 degrees C and in warm-acclimated (WA) cardiomyocytes tested at 19 degrees C compared with 24 degrees C. This effect was mirrored by a decrease in the density of the delayed-rectifier current (I(Kr)), whereas the density of the background inward-rectifier current (I(K1)) was unchanged. When CA and WA cardiomyocytes were tested at a common temperature of 19 degrees C, no significant effects of temperature acclimation on AP shape or duration were observed, whereas I(Kr) density was markedly increased in CA cardiomyocytes. I(K1) density was unaffected in CA ventricular myocytes but was significantly reduced in CA atrial myocytes, resulting in a depolarization of atrial resting membrane potential. Our results indicate the bluefin AP is relatively short compared with other teleosts, which may allow the bluefin heart to function at cold temperatures without the necessity for thermal

  13. Acetylcholinesterase antagonist potentiated insulin action in fed but not fasted state.

    PubMed

    Schafer, Joshua; Legare, Dallas J; Lautt, W Wayne

    2010-05-01

    The glucose disposal effect of insulin is doubled in response to a meal. This meal-induced insulin sensitization results from insulin acting on the liver, in the presence of a permissive hepatic parasympathetic feeding signal and elevated hepatic glutathione (GSH), to release hepatic insulin-sensitizing substance (HISS), a hormone that acts selectively on skeletal muscle to stimulate insulin-mediated glucose uptake. Blockade of the parasympathetic feeding signal to the liver, either through surgical denervation or atropine-mediated antagonism of hepatic muscarinic receptors, eliminates the HISS response, resulting in HISS-dependent insulin resistance (HDIR) and decreasing the response to insulin by approximately 55% in the fed state. Insulin action in Sprague-Dawley rats, as determined with a rapidly sampled, transient euglycemic clamp in response to insulin (50 mU/kg), is decreased in a dose-dependent manner by atropine. In this study, we have used the ED75 atropine-induced model of HDIR. After a submaximal dose of atropine, potentiation of the remaining parasympathetic effect with the acetylcholinesterase antagonist neostigmine significantly restored postprandial insulin sensitization in a dose-dependent manner with peak effect at 0.1 microg/kg/min. Neostigmine reversed the insulin resistance induced by partial fasting and partial muscarinic inhibition (hepatic GSH levels are at fed levels), but not that induced by surgical hepatic denervation (GSH normal, no nerve signal) or 24-h fasting (low GSH). No potentiation of the response to insulin by neostigmine occurred in normal, fed rats. The data suggest the use of either direct or indirectly acting cholinergic agonists for the treatment of impaired postprandial insulin sensitization.

  14. 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

  15. 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.

  16. The effects of ventricular end-diastolic and systolic pressures on action potential and duration in anaesthetized dogs.

    PubMed Central

    Coulshed, D S; Cowan, J C; Drinkhill, M J; Hainsworth, R

    1992-01-01

    1. Although it is known that mechanical events in the heart influence the duration of the cardiac action potential, there is no quantitative information on the effects of independent changes in ventricular end-diastolic and systolic pressures. 2. Experiments were carried out on open-chest anaesthetized dogs in which the autonomic nervous influences on the heart were prevented and monophasic action potentials were recorded form the epicardial surface of the left ventricle. The duration of these action potentials was taken as the interval from the upstroke to the point of 90% repolarization. 3. Elevation of left ventricular peak systolic pressure, at constant end-diastolic pressure, significantly shortened the monophasic action potential. 4. Elevation of end-diastolic pressure at constant peak systolic pressure significantly lengthened the monophasic action potential. 5. Responses were not dependent on release of noradrenaline from sympathetic nerve terminals because they persisted after administration of bretylium tosylate. They were also not due to myocardial ischaemia because they persisted when coronary perfusion pressure was maintained at a constant high level. 6. Simultaneous recordings of changes in myocardial segment length showed the expected responses to changes in ventricular pressures: increases in shortening in response to increases in diastolic pressure and no consistent effect from changes in systolic pressure. 7. These investigations demonstrate the independent effects of changes in systolic and end-diastolic pressures on cardiac action potential duration. This effect is likely to be an effect of the mechanical events, i.e. contraction-excitation feedback. This response may be mediated through changes in myocardial fibre tension, the consequent changes in fibre shortening, or both. PMID:1297849

  17. Atria selective prolongation by NIP-142, an antiarrhythmic agent, of refractory period and action potential duration in guinea pig myocardium.

    PubMed

    Matsuda, Tomoyuki; Takeda, Kentaro; Ito, Mie; Yamagishi, Reiko; Tamura, Miku; Nakamura, Hideki; Tsuruoka, Noriko; Saito, Tomoaki; Masumiya, Haruko; Suzuki, Takeshi; Iida-Tanaka, Naoko; Itokawa-Matsuda, Maho; Yamashita, Toru; Tsuruzoe, Nobutomo; Tanaka, Hikaru; Shigenobu, Koki

    2005-05-01

    NIP-142 is a novel benzopyran compound that was shown to prolong the atrial effective refractory period and terminate experimental atrial fibrillation in the dog. In the present study, we examined the effects of NIP-142 on isolated guinea pig myocardium and on the G-protein-coupled inwardly rectifying potassium channel current (acetylcholine-activated potassium current; I(KACh)) expressed in Xenopus oocytes. NIP-142 (10 and 100 microM) concentration-dependently prolonged the refractory period and action potential duration in the atrium but not in the ventricle. E-4031 and 4-aminopyridine prolonged action potential duration in both left atrium and right ventricle. Prolongation by NIP-142 of the atrial action potential duration was observed at stimulation frequencies between 0.5 and 5 Hz. In contrast, the prolongation by E-4031 was not observed at higher frequencies. Tertiapin, a blocker of I(KACh), prolonged action potential duration in the atrium but not in the ventricle. NIP-142 completely reversed the carbachol-induced shortening of atrial action potential duration. NIP-142 (1 to 100 microM), as well as tertiapin (0.1 to 100 nM), concentration-dependently blocked I(KACh) expressed in Xenopus oocytes; the blockade by NIP-142 was not affected by membrane voltage. In conclusion, NIP-142 was shown to prolong atrial refractory period and action potential duration through blockade of I(KACh) which may possibly explain its previously described antiarrhythmic activity. NIP-142 has pharmacological properties that are different from classical class III antiarrhythmic agents such as atria specificity and lack of reverse frequency dependence, and thus appears promising for the treatment of supraventricular arrhythmia.

  18. Resilient RTN fast spiking in Kv3.1 null mice suggests redundancy in the action potential repolarization mechanism.

    PubMed

    Porcello, Darrell M; Ho, Chi Shun; Joho, Rolf H; Huguenard, John R

    2002-03-01

    Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K(+) channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23 degrees C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1(-/-)) compared with their wild-type (Kv3.1(+/+)) counterparts had reduced amplitudes (-6%) and fast after-hyperpolarizations (-16%). At 34 degrees C, action potentials in Kv3.1(-/-) mice had increased duration (21%) due to a reduced rate of repolarization (-30%) when compared with wild-type controls. Action potential trains in Kv3.1(-/-) were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship (F/I) at 34 degrees C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca(2+) bursts in Kv3.1(-/-) RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.

  19. Quantum dynamics via Planck-scale-stepped action-carrying 'Graph Paths'

    SciTech Connect

    Chew, Geoffrey F.

    2003-05-05

    A divergence-free, parameter-free, path-based discrete-time quantum dynamics is designed to not only enlarge the achievements of general relativity and the standard particle model, by approximations at spacetime scales far above Planck scale while far below Hubble scale, but to allow tackling of hitherto inaccessible questions. ''Path space'' is larger than and precursor to Hilbert-space basis. The wave-function-propagating paths are action-carrying structured graphs-cubic and quartic structured vertices connected by structured ''fermionic'' or ''bosonic'' ''particle'' and ''nonparticle'' arcs. A Planck-scale path step determines the gravitational constant while controlling all graph structure. The basis of the theory's (zero-rest-mass) elementary-particle Hilbert space (which includes neither gravitons nor scalar bosons) resides in particle arcs. Nonparticle arcs within a path are responsible for energy and rest mass.

  20. Dynamical back-action at 5.5 GHz in a corrugated optomechanical beam

    SciTech Connect

    Navarro-Urrios, D.; Gomis-Bresco, J.; Alzina, F.; El-Jallal, S.; Oudich, M.; Pennec, Y.; Djafari-Rouhani, B.; Pitanti, A.; Capuj, N.; Tredicucci, A.; Griol, A.; Martínez, A.; Sotomayor Torres, C. M.

    2014-12-15

    We report on the optomechanical properties of a breathing mechanical mode oscillating at 5.5 GHz in a 1D corrugated Si nanobeam. This mode has an experimental single-particle optomechanical coupling rate of |g{sub o,OM}| = 1.8 MHz (|g{sub o,OM}|/2π = 0.3 MHz) and shows strong dynamical back-action effects at room temperature. The geometrical flexibility of the unit-cell would lend itself to further engineering of the cavity region to localize the mode within the full phononic band-gap present at 4 GHz while keeping high g{sub o,OM} values. This would lead to longer lifetimes at cryogenic temperatures, due to the suppression of acoustic leakage.

  1. The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin.

    PubMed

    Rooke, N; Li, D J; Li, J; Keung, W M

    2000-11-02

    Recent studies showed that daidzin suppresses ethanol intake in ethanol-preferring laboratory animals. In vitro, it potently and selectively inhibits the mitochondrial aldehyde dehydrogenase (ALDH-2). Further, it inhibits the conversion of monoamines such as serotonin (5-HT) and dopamine (DA) into their respective acid metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in isolated hamster or rat liver mitochondria. Studies on the suppression of ethanol intake and inhibition of 5-HIAA (or DOPAC) formation by six structural analogues of daidzin suggested a potential link between these two activities. This, together with the finding that daidzin does not affect the rates of mitochondria-catalyzed oxidative deamination of these monoamines, raised the possibility that the ethanol intake-suppressive (antidipsotropic) action of daidzin is not mediated by the monoamines but rather by their reactive biogenic aldehyde intermediates such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or 3,4-dihydroxyphenylacetaldehyde (DOPAL) which accumulate in the presence of daidzin. To further evaluate this possibility, we synthesized more structural analogues of daidzin and tested and compared their antidipsotropic activities in Syrian golden hamsters with their effects on monoamine metabolism in isolated hamster liver mitochondria using 5-HT as the substrate. Effects of daidzin and its structural analogues on the activities of monoamine oxidase (MAO) and ALDH-2, the key enzymes involved in 5-HT metabolism in the mitochondria, were also examined. Results from these studies reveal a positive correlation between the antidipsotropic activities of these analogues and their abilities to increase 5-HIAL accumulation during 5-HT metabolism in isolated hamster liver mitochondria. Daidzin analogues that potently inhibit ALDH-2 but have no or little effect on MAO are most antidipsotropic, whereas those that also potently inhibit MAO exhibit little, if

  2. 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

  3. A Subspace Method for Dynamical Estimation of Evoked Potentials

    PubMed Central

    Georgiadis, Stefanos D.; Ranta-aho, Perttu O.; Tarvainen, Mika P.; Karjalainen, Pasi A.

    2007-01-01

    It is a challenge in evoked potential (EP) analysis to incorporate prior physiological knowledge for estimation. In this paper, we address the problem of single-channel trial-to-trial EP characteristics estimation. Prior information about phase-locked properties of the EPs is assesed by means of estimated signal subspace and eigenvalue decomposition. Then for those situations that dynamic fluctuations from stimulus-to-stimulus could be expected, prior information can be exploited by means of state-space modeling and recursive Bayesian mean square estimation methods (Kalman filtering and smoothing). We demonstrate that a few dominant eigenvectors of the data correlation matrix are able to model trend-like changes of some component of the EPs, and that Kalman smoother algorithm is to be preferred in terms of better tracking capabilities and mean square error reduction. We also demonstrate the effect of strong artifacts, particularly eye blinks, on the quality of the signal subspace and EP estimates by means of independent component analysis applied as a prepossessing step on the multichannel measurements. PMID:18288257

  4. Biology and dynamics of potential malaria vectors in Southern France

    PubMed Central

    Ponçon, Nicolas; Toty, Céline; L'Ambert, Grégory; Le Goff, Gilbert; Brengues, Cécile; Schaffner, Francis; Fontenille, Didier

    2007-01-01

    Background Malaria is a former endemic problem in the Camargue, South East France, an area from where very few recent data concerning Anopheles are available. A study was undertaken in 2005 to establish potential malaria vector biology and dynamics and evaluate the risk of malaria re-emergence. Methods Mosquitoes were collected in two study areas, from March to October 2005, one week every two weeks, using light traps+CO2, horse bait traps, human bait catch, and by collecting females in resting sites. Results Anopheles hyrcanus was the most abundant Anopheles species. Anoph