Calcium‐activated non‐selective cation channel in ventricular cells isolated from adult guinea‐pig hearts.

Ehara, Tsuguhisa; Noma, Akinori; Ono, Koichi

doi:10.1113/jphysiol.1988.sp017242

Cited by 191 publications

(120 citation statements)

References 39 publications

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“…Voltage steps were presented in 10 mV increments at 10 s intervals unless otherwise noted. All experimental par,meters, such as holding potentials, test potentials, etc., were controlled with an IBM-PC, equipped with a Teemar Labmaster analog-digital interface (Scientific Solutions) to the electrophysiological equipment, using the pClamp software package (v 4 (Ehara, Noma & Ono, 1988). Data analyses.…”

Section: Methodsmentioning

confidence: 99%

Interconversion between distinct gating pathways of the high threshold calcium channel in rat ventricular myocytes.

Richard

Charnet

Nerbonne

1993

The Journal of Physiology

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Section: Methodsmentioning

confidence: 99%

Interconversion between distinct gating pathways of the high threshold calcium channel in rat ventricular myocytes.

Richard

Charnet

Nerbonne

1993

The Journal of Physiology

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“…Definitions: I Na , fast sodium current; I Ca(L) , calcium current through L-type calcium channels; I Ca(T) , calcium current through T-type calcium channels (Droogmans & Nilius, 1989;Balke et al 1992;Vassort & Alvarez, 1994); I Kr , rapid delayed rectifier potassium current Silva & Rudy, 2005); I Ks , slow delayed rectifier potassium current (Silva & Rudy, 2005); I K 1 , inward rectifier potassium current (Kurachi, 1985); I Kp , plateau potassium current (Yue & Marban, 1988;Backx & Marban, 1993); I Na,b , sodium background current; I Ca,b , calcium background current; I NaK , sodium-potassium pump current; I NaCa , sodium-calcium exchange current; I p(Ca) calcium pump in the sarcolemma (Caroni et al 1983); I up , calcium uptake from the myoplasm to network sarcoplasmic reticulum (NSR) (Tada et al 1989); I rel , calcium release from junctional sarcoplasmic reticulum ( JSR) (Meissner, 1995); I leak , calcium leakage from NSR to myoplasm; I tr , calcium translocation from NSR to JSR (Yue et al 1985). The following currents (shaded in the figure) are included under pathological conditions: I K(ATP) , ATPsensitive potassium current, activated under conditions of ATP depletion (ischemia) (Kakei et al 1985;Nichols et al 1991;Noma, 1983;Shaw & Rudy, 1997a); I K(Na) , sodium-activated potassium current, activated under conditions of sodium overload (Kameyama et al 1984;Luk & Carmeliet, 1990;Wang et al 1991;Faber & Rudy, 2000); I ns(Ca) , non-specific calciumactivated current, activated under conditions of calcium overload (Ehara et al 1988;Luo & Rudy, 1994b); Calmodulin and troponin represent calcium buffers in the myoplasm. Calsequestrin is a calcium buffer in the JSR.…”

Section: Epiloguementioning

confidence: 99%

Computational biology in the study of cardiac ion channels and cell electrophysiology

Rudy

Silva

2006

Quart. Rev. Biophys.

238

181

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The cardiac cell is a complex biological system where various processes interact to generate electrical excitation (the action potential, AP) and contraction. During AP generation, membrane ion channels interact nonlinearly with dynamically changing ionic concentrations and varying transmembrane voltage, and are subject to regulatory processes. In recent years, a large body of knowledge has accumulated on the molecular structure of cardiac ion channels, their function, and their modification by genetic mutations that are associated with cardiac arrhythmias and sudden death. However, ion channels are typically studied in isolation (in expression systems or isolated membrane patches), away from the physiological environment of the cell where they interact to generate the AP. A major challenge remains the integration of ion-channel properties into the functioning, complex and highly interactive cell system, with the objective to relate molecular-level processes and their modification by disease to whole-cell function and clinical phenotype. In this article we describe how computational biology can be used to achieve such integration. We explain how mathematical (Markov) models of ion-channel kinetics are incorporated into integrated models of cardiac cells to compute the AP. We provide examples of mathematical (computer) simulations of physiological and pathological phenomena, including AP adaptation to changes in heart rate, genetic mutations in SCN5A and HERG genes that are associated with fatal cardiac arrhythmias, and effects of the CaMKII regulatory pathway and β-adrenergic cascade on the cell electrophysiological function. Prologue'Things should be made as simple as possible, but not any simpler.' Albert EinsteinCardiac muscle can generate propagating electrical impulses (action potentials), a property that classifies it as an excitable tissue similar to skeletal muscle and nerve. At the single-cell level, the electrical action potential (AP) triggers mechanical contraction by inducing a transient rise of intracellular calcium which, in turn, carries the contraction message to the contractile proteins of the cell. This process that couples electrical excitation to mechanical function is termed excitation-contraction coupling. APs are generated by individual cells and are conducted from cell to cell through intercellular gap junctions, forming waves of excitation that activate and synchronize the blood pumping action of the heart. Similar to nerve and skeletal muscle, AP initiation and conduction in cardiac ventricular tissue rely mostly on a single membrane process, namely the flow of sodium ions through sodium-specific ion channels. However, unlike the short-duration APs of skeletal muscle and nerve, the cardiac ventricular AP is characterized by long plateau and repolarization phases that prevent premature arrhythmogenic excitation and provide control of mechanical contraction. In NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript contrast to the 'single-current mechanism' of...

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“…Lithium is known to enter the cell via Na+ channels (Carmeliet, 1964) and calciumactivated non-selective cation channels (Ehara et al 1988). On the other hand, Li+ substitutes very little for Na+ in the Na+-Ca2+ exchange mechanism (Kadoma, Froehlich, Reeves & Sutko, 1982).…”

Section: Effect Of Na+ and Ca2+ Concentrationsmentioning

confidence: 99%

“…Most authors suggest that these currents may 50 CONTRACTION-RELATED SLOW INWARD CURRENT be accounted for by the electrogenic Na+-Ca2+ exchange process. The second of the so far defined mechanisms of Ca2+-activated inward current, a non-specific cation channel (Colquhoun, Neher, Reuter & Stevens, 1981; Ehara, Noma & Ono, 1988) is, however, also considered.…”

Section: Introductionmentioning

confidence: 99%

A contraction‐related component of slow inward current in dog ventricular muscle and its relation to Na(+)‐Ca2+ exchange.

Šimurda

Šimurdová

Bravený

et al. 1992

The Journal of Physiology

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SUMMARY1. The slow inward current component related to contraction (Ii,) was studied in voltage clamp experiments on canine ventricular trabeculae at 30 0C with the aims of (a) estimating its relation to electrogenic Na+-Ca2+ exchange and (b) comparing it with similar currents as reported in cardiac myocytes.2. Ii, may be recorded under conditions of augmented contractility in response to depolarizing pulses below the threshold of the classic slow inward current (presumably mediated by L-type Ca2+ channels). In responses to identical depolarizing clamp pulses the peak value of 1sic is directly related to the amplitude of contraction (Fmax). Isic peaks about 60 ms after the onset of depolarization and declines with a half-time of about 110 ms.3. The voltage threshold of Isic activation is the same as the threshold of contraction. The positive inotropic clamp preconditions shift both thresholds to more negative values of membrane voltage, i.e. below the threshold of the classic slow inward current.4. Ij, may also be recorded as a slowly decaying inwardly directed current 'tail' after depolarizing pulses. In this representation the peak value of I~j, changes with duration of the depolarizing pulses, again in parallel with Fmax. In response to pulses shorter than 100 ms both variables increase with depolarization time. If initial conditions remain constant, further prolongation of the pulse does not significantly influence either one (tail currents follow a common envelope).5. Ij, differs from classic slow inward current by: (a) its direct relation to contraction, (b) the slower decay of the current tail on repolarization, (c) slower restitution corresponding to the mechanical restitution, (d) its relative insensitivity to Ca2+-blocking agents (the decrease of I.ij is secondary to the negative inotropic effect) and (e) its disappearance after Sr2+ substitution for Ca2+.6. The manifestations ofIsic in multicellular preparations do not differ significantly from those reported in isolated myocytes (in contrast to calcium current).7.

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Calcium‐activated non‐selective cation channel in ventricular cells isolated from adult guinea‐pig hearts.

Cited by 191 publications

References 39 publications

Interconversion between distinct gating pathways of the high threshold calcium channel in rat ventricular myocytes.

Interconversion between distinct gating pathways of the high threshold calcium channel in rat ventricular myocytes.

Computational biology in the study of cardiac ion channels and cell electrophysiology

A contraction‐related component of slow inward current in dog ventricular muscle and its relation to Na(+)‐Ca2+ exchange.

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