scholarly journals Effects of Na+Current and Mechanogated Channels in Myofibroblasts on Myocyte Excitability and Repolarization

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Heqing Zhan ◽  
Jingtao Zhang ◽  
Jialun Lin ◽  
Guilai Han
Keyword(s):  
Mathematical Modeling ◽  
Membrane Potential ◽  
Action Potential ◽  
Channel Current ◽  
Voltage Gated Sodium Channels ◽  
Atrial Myocyte ◽  
Experimental Findings ◽  
Human Atrial Myocyte ◽  
Coupling Conductance ◽  
Basic Cycle Length

Fibrotic remodeling, characterized by fibroblast phenotype switching, is often associated with atrial fibrillation and heart failure. This study aimed to investigate the effects on electrotonic myofibroblast-myocyte (Mfb-M) coupling on cardiac myocytes excitability and repolarization of the voltage-gated sodium channels (VGSCs) and single mechanogated channels (MGCs) in human atrial Mfbs. Mathematical modeling was developed from a combination of (1) models of the human atrial myocyte (including the stretch activated ion channel current,ISAC) and Mfb and (2) our formulation of currents through VGSCs (INa_Mfb) and MGCs (IMGC_Mfb) based upon experimental findings. The effects of changes in the intercellular coupling conductance, the number of coupled Mfbs, and the basic cycle length on the myocyte action potential were simulated. The results demonstrated that the integration ofISAC,INa_Mfb, andIMGC_Mfbreduced the amplitude of the myocyte membrane potential(Vmax)and the action potential duration (APD), increased the depolarization of the resting myocyte membrane potential(Vrest), and made it easy to trigger spontaneous excitement in myocytes. For Mfbs, significant electrotonic depolarizations were exhibited with the addition ofINa_MfbandIMGC_Mfb. Our results indicated thatISAC,INa_Mfb, andIMGC_Mfbsignificantly influenced myocytes and Mfbs properties and should be considered in future cardiac pathological mathematical modeling.

scholarly journals K+current changes account for the rate dependence of the action potential in the human atrial myocyte

2009 ◽  
Vol 297 (4) ◽  
pp. H1398-H1410 ◽  
Author(s):  
Mary M. Maleckar ◽  
Joseph L. Greenstein ◽  
Wayne R. Giles ◽  
Natalia A. Trayanova
Keyword(s):  
Action Potential ◽  
Membrane Dynamics ◽  
Rate Dependence ◽  
Accurate Representation ◽  
New Model ◽  
Charge Conservation ◽  
Repolarization Reserve ◽  
Atrial Myocyte ◽  
Kinetics Of ◽  
Human Atrial Myocyte

Ongoing investigation of the electrophysiology and pathophysiology of the human atria requires an accurate representation of the membrane dynamics of the human atrial myocyte. However, existing models of the human atrial myocyte action potential do not accurately reproduce experimental observations with respect to the kinetics of key repolarizing currents or rate dependence of the action potential and fail to properly enforce charge conservation, an essential characteristic in any model of the cardiac membrane. In addition, recent advances in experimental methods have resulted in new data regarding the kinetics of repolarizing currents in the human atria. The goal of this study was to develop a new model of the human atrial action potential, based on the Nygren et al. model of the human atrial myocyte and newly available experimental data, that ensures an accurate representation of repolarization processes and reproduction of action potential rate dependence and enforces charge conservation. Specifically, the transient outward K+current ( It) and ultrarapid rectifier K+current ( IKur) were newly formulated. The inwardly recitifying K+current ( IK1) was also reanalyzed and implemented appropriately. Simulations of the human atrial myocyte action potential with this new model demonstrated that early repolarization is dependent on the relative conductances of Itand IKur, whereas densities of both IKurand IK1underlie later repolarization. In addition, this model reproduces experimental measurements of rate dependence of It, IKur, and action potential duration. This new model constitutes an improved representation of excitability and repolarization reserve in the human atrial myocyte and, therefore, provides a useful computational tool for future studies involving the human atrium in both health and disease.

scholarly journals Stretch-activated current in human atrial myocytes and Na+ current and mechano-gated channels’ current in myofibroblasts alter myocyte mechanical behavior: a computational study

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Heqing Zhan ◽  
Jingtao Zhang ◽  
Anquan Jiao ◽  
Qin Wang
Keyword(s):  
Mathematical Modeling ◽  
Mechanical Behavior ◽  
Cycle Length ◽  
Computational Study ◽  
Mechanical Parameters ◽  
Intercellular Coupling ◽  
Force Relation ◽  
Increased Risk ◽  
Coupling Conductance ◽  
Basic Cycle Length

Abstract Background The activation of stretch-activated channels (SACs) in cardiac myocytes, which changes the phases of action potential repolarization, is proven to be highly efficient for the conversion of atrial fibrillation. The expression of Na+ current in myofibroblasts (Mfbs) regenerates myocytes’ action potentials, suggesting that Mfbs play an active role in triggering cardiac rhythm disturbances. Moreover, the excitation of mechano-gated channels (MGCs) in Mfbs depolarizes their membrane potential and contributes to the increased risk of post-infarct arrhythmia. Although these electrophysiological mechanisms have been largely known, the roles of these currents in cardiac mechanics are still debated. In this study, we aimed to investigate the mechanical influence of these currents via mathematical modeling. A novel mathematical model was developed by integrating models of human atrial myocyte (including the stretch-activated current, Ca2+–force relation, and mechanical behavior of a single segment) and Mfb (including our formulation of Na+ current and mechano-gated channels’ current). The effects of the changes in basic cycle length, number of coupled Mfbs and intercellular coupling conductance on myocyte mechanical properties were compared. Results Our results indicated that these three currents significantly regulated myocyte mechanical parameters. In isosarcometric contraction, these currents increased segment force by 13.8–36.6% and dropped element length by 12.1–31.5%. In isotonic contraction, there are 2.7–5.9% growth and 0.9–24% reduction. Effects of these currents on the extremum of myocyte mechanical parameters become more significant with the increase of basic cycle length, number of coupled Mfbs and intercellular coupling conductance. Conclusions The results demonstrated that stretch-activated current in myocytes and Na+ current and mechano-gated channels’ current in Mfbs significantly influenced myocyte mechanical behavior and should be considered in future cardiac mechanical mathematical modeling.

scholarly journals Excitation-Contraction Coupling between Human Atrial Myocytes with Fibroblasts and Stretch Activated Channel Current: A Simulation Study

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Heqing Zhan ◽  
Ling Xia
Keyword(s):  
Simulation Study ◽  
Mechanical Model ◽  
Tissue Level ◽  
Resting Membrane Potential ◽  
Cardiac Modeling ◽  
Electrical Excitation ◽  
Channel Current ◽  
Modeling Studies ◽  
Atrial Myocyte ◽  
Human Atrial Myocyte

Myocytes have been regarded as the main objectives in most cardiac modeling studies and attracted a lot of attention. Connective tissue cells, such as fibroblasts (Fbs), also play crucial role in cardiac function. This study proposed an integrated myocyte-Isac-Fb electromechanical model to investigate the effect of Fbs and stretch activated ion channel current (Isac) on cardiac electrical excitation conduction and mechanical contraction. At the cellular level, an active Fb model was coupled with a human atrial myocyte electrophysiological model (includingIsac) and a mechanical model. At the tissue level, electrical excitation conduction was coupled with an elastic mechanical model, in which finite difference method (FDM) was used to solve the electrical excitation equations, while finite element method (FEM) was used for the mechanics equations. The simulation results showed that Fbs andIsaccoupling caused diverse effects on action potential morphology during repolarization, depolarized the resting membrane potential of the human atrial myocyte, slowed down wave propagation, and decreased strains in fibrotic tissue. This preliminary simulation study indicates that Fbs andIsachave important implications for modulating cardiac electromechanical behavior and should be considered in future cardiac modeling studies.

I(to) and action potential notch are smaller in left vs. right canine ventricular epicardium

1996 ◽  
Vol 271 (2) ◽  
pp. H548-H561 ◽  
Author(s):  
J. M. Di Diego ◽  
Z. Q. Sun ◽  
C. Antzelevitch
Keyword(s):  
Action Potential ◽  
Phase 1 ◽  
Outward Current ◽  
Disulfonic Acid ◽  
Transient Outward Current ◽  
Pharmacological Agents ◽  
Whole Cell Patch Clamp ◽  
Chloride Channel Blocker ◽  
The Right ◽  
Basic Cycle Length

Transmural heterogeneities of repolarizing currents underlie prominent differences in the electrophysiology and pharmacology of ventricular epicardial, endocardial, and M cells in a number of species. The degree to which heterogeneities exist between the right and left ventricles is not well appreciated. The present study uses standard microelectrode and whole cell patch-clamp techniques to contrast the electrophysiological characteristics and pharmacological responsiveness of tissues and myocytes isolated from right (RVE) and left canine ventricular epicardium (LVE). RVE and LVE studied under nearly identical conditions displayed major differences in the early repolarizing phases of the action potential. The magnitude of phase 1 in RVE was nearly threefold that in LVE: 28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV (basic cycle length = 2,000 ms). Phase 1 in RVE was also more sensitive to alterations of the stimulation rate and to 4-aminopyridine (4-AP), suggesting a much greater contribution of the transient outward current (I(to) 1) in RVE than in LVE. The combination of 4-AP plus ryanodine, low chloride, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (chloride channel blocker) completely eliminated the notch and all rate dependence of the early phases of the action potential, making RVE and LVE indistinguishable. At +70 mV, RVE myocytes displayed peak I(to) 1 densities between 28 and 37 pA/pF. LVE myocytes included cells with similar I(to) 1 densities (thought to represent subsurface cells) but also cells with much smaller current levels (thought to represent surface cells). Average peak I(to) 1 density was significantly smaller in LVE than in RVE at voltages more than or equal to +10 mV. Our data point to prominent differences in the magnitude of the I(to) 1-mediated action potential notch in cells at the surface of RVE compared with the LVE and suggest that important distinctions may exist in the response of these two tissues to pharmacological agents and pathophysiological states, as previously demonstrated for epicardium and endocardium. Our findings also suggest that a calcium-activated outward current contributes to the early repolarization phase in RVE and LVE and that the influence of this current, although small, is more important in the left ventricle.

Effects of some divalent cations on motoneurones in cats

1979 ◽  
Vol 57 (9) ◽  
pp. 944-956 ◽  
Author(s):  
K. Krnjević ◽  
Y. Lamour ◽  
J. F. MacDonald ◽  
A. Nistri
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Intracellular Recording ◽  
Dorsal Root ◽  
Divalent Cations ◽  
The Other ◽  
Depressant Effect ◽  
Na Inactivation ◽  
Conductance Increase ◽  
Root Stimulation

In cats under Dial, Co, Mn, La, and Sr were injected extracellularly near lumbosacral motoneurones. All tended to improve intracellular recording, but when the membrane potential was initially stable, Mn, and especially Co, had a moderate and reproducible depolarizing action. Both Mn and Co depressed excitatory postsynaptic potentials evoked by dorsal root stimulation. The prominent after-hyperpolarization (a.h.p.), which normally follows the motoneuronal action potential, was consistently and reversibly depressed by Mn and Co (as well as La), the underlying conductance increase being also diminished, but there was no significant reduction in the after-depolarization. By contrast, Sr tended to potentiate the a.h.p., especially when this was depressed by a previous injection of Co or Mn. Unlike the other cations, Co had a marked depressant effect on the action potential, particularly its rate of rise. Since the action potential could be immediately restored by hyperpolarization or by an injection of Sr (in the absence of depolarization), Co may enhance Na inactivation.

Modulation of membrane potential by an acetylcholine-activated potassium current in trout atrial myocytes

2007 ◽  
Vol 292 (1) ◽  
pp. R388-R395 ◽  
Author(s):  
Cristina E. Molina ◽  
Hans Gesser ◽  
Anna Llach ◽  
Lluis Tort ◽  
Leif Hove-Madsen
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Atrial Myocytes ◽  
Atrial Tissue ◽  
Isolated Cardiac Myocytes ◽  
Inwardly Rectifying

Application of the current-clamp technique in rainbow trout atrial myocytes has yielded resting membrane potentials that are incompatible with normal atrial function. To investigate this paradox, we recorded the whole membrane current ( Im) and compared membrane potentials recorded in isolated cardiac myocytes and multicellular preparations. Atrial tissue and ventricular myocytes had stable resting potentials of −87 ± 2 mV and −83.9 ± 0.4 mV, respectively. In contrast, 50 out of 59 atrial myocytes had unstable depolarized membrane potentials that were sensitive to the holding current. We hypothesized that this is at least partly due to a small slope conductance of Im around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of Im was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased Im at −120 mV from 4.3 pA/pF to 27 pA/pF with an EC50 of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of Im fourfold, shifted its reversal potential from −78 ± 3 to −84 ± 3 mV, and stabilized the resting membrane potential at −92 ± 4 mV. ACh also shortened the action potential in both atrial myocytes and tissue, and this effect was antagonized by atropine. When applied alone, atropine prolonged the action potential in atrial tissue but had no effect on membrane potential, action potential, or Im in isolated atrial myocytes. This suggests that ACh-mediated activation of an inwardly rectifying K+ current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential.

Exposure to low temperature prepares the turtle brain to withstand anoxic environments during overwintering

2021 ◽  
Author(s):  
Ebrahim Lari ◽  
Leslie T. Buck
Keyword(s):  
Membrane Potential ◽  
Low Temperature ◽  
Action Potential ◽  
Pyramidal Neurons ◽  
Cellular Damage ◽  
Severe Hypoxia ◽  
Painted Turtle ◽  
Whole Cell ◽  
Voltage Gated ◽  
The Impact

In most vertebrates, anoxia drastically reduces the production of the essential adenosine triphosphate (ATP) to power its many necessary functions, and consequently, cell death occurs within minutes. However, some vertebrates, such as the painted turtle (Chrysemys picta bellii), have evolved the ability to survive months without oxygen by simultaneously decreasing ATP supply and demand, surviving the anoxic period without any apparent cellular damage. The impact of anoxia on the metabolic function of painted turtles has received a lot of attention. Still, the impact of low temperature has received less attention and the interactive effect of anoxia and temperature even less. In the present study, we investigated the interactive impacts of reduced temperature and severe hypoxia on the electrophysiological properties of pyramidal neurons in painted turtle cerebral cortex. Our results show that an acute reduction in temperature from 20 to 5°C decreases membrane potential, action potential width and amplitude, and whole-cell conductance. Importantly, acute exposure to 5°C considerably slows membrane repolarization by voltage-gated K+ channels. Exposing pyramidal cells to severe hypoxia in addition to an acute temperature change slightly depolarized membrane potential but did not alter action potential amplitude or width and whole-cell conductance. These results suggest that acclimation to low temperatures, preceding severe environmental hypoxia, induces cellular responses in pyramidal neurons that facilitate survival under low oxygen concentration. In particular, our results show that temperature acclimation invokes a change in voltage-gated K+ channel kinetics that overcomes the acute inhibition of the channel.

Basic electrophysiological properties of spinal cord motoneurons during old age in the cat

1987 ◽  
Vol 58 (1) ◽  
pp. 180-194 ◽  
Author(s):  
F. R. Morales ◽  
P. A. Boxer ◽  
S. J. Fung ◽  
M. H. Chase
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Action Potential ◽  
Old Age ◽  
Conduction Velocity ◽  
Input Resistance ◽  
Action Potential Amplitude ◽  
Electrophysiological Properties ◽  
Potential Amplitude ◽  
Versus Input

1. The electrophysiological properties of alpha-motoneurons in old cats (14–15 yr) were compared with those of adult cats (1–3 yr). These properties were measured utilizing intracellular recording and stimulating techniques. 2. Unaltered in the old cat motoneurons were the membrane potential, action potential amplitude, and slopes of the initial segment (IS) and soma dendritic (SD) spikes, as well as the duration and amplitude of the action potential's afterhyperpolarization. 3. In contrast, the following changes in the electrophysiological properties of lumbar motoneurons were found in the old cats: a decrease in axonal conduction velocity, a shortening of the IS-SD delay, an increase in input resistance, and a decrease in rheobase. 4. In spite of these considerable changes in motoneuron properties in the old cat, normal correlations between different electrophysiological properties were maintained. The following key relationships, among others, were the same in adult and old cat motoneurons: membrane potential polarization versus action potential amplitude, duration of the afterhyperpolarization versus motor axon conduction velocity, and rheobase versus input conductance. 5. A review of the existing literature reveals that neither chronic spinal cord section nor deafferentation (13, 21) in adult animals produce the changes observed in old cats. Thus we consider it unlikely that a loss of synaptic contacts was responsible for the modifications in electrophysiological properties observed in old cat motoneurons. 6. We conclude that during old age there are significant changes in the soma-dendritic portion of cat motoneurons, as indicated by the modifications found in input resistance, rheobase, and IS-SD delay, as well as significant changes in their axons, as indicated by a decrease in conduction velocity.

A model of beta-adrenergic effects on calcium and potassium current in bullfrog atrial myocytes

1991 ◽  
Vol 261 (6) ◽  
pp. H1937-H1944
Author(s):  
J. M. Shumaker ◽  
J. W. Clark ◽  
W. R. Giles
Keyword(s):  
Action Potential ◽  
Potassium Current ◽  
Beta Adrenergic ◽  
Calcium Dependent ◽  
Dependent Inactivation ◽  
Atrial Myocyte ◽  
Muscarinic Cholinergic ◽  
High Doses ◽  
Dose Dependent ◽  
Cholinergic Effects

A model of beta-adrenergic and muscarinic cholinergic effects on the bullfrog atrial myocyte has been developed to simulate the dose-dependent effects of isoprenaline (Iso) on the action potential duration (APD); i.e., low doses of Iso lengthen the APD, whereas high doses shorten the APD. In this model, the reduction in APD is the result of 1) calcium-dependent inactivation of calcium current (ICa) resulting from the enhancement of ICa by Iso and 2) an enhancement of potassium current (IK) due to both an Iso-induced increase in the rate of activation of IK and an increase in peak action potential height. The effect of acetylcholine (ACh) is simulated by a reduction in the Iso-induced increase in ICa and IK through a reduction in relative adenosine 3',5'-cyclic monophosphate concentration ([cAMP]), as well as activation of the ACh-sensitive potassium current. At low [Iso] levels in the presence of a high [ACh], the muscarinic cholinergic effects dominate the beta-adrenergic change. However, for a large [Iso] and a small [ACh], this pattern of changes in transmembrane currents is different; in this case the model predicts that ACh can actually increase APD.

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