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(Circulation Research. 2007;101:533.)
© 2007 American Heart Association, Inc.

Editorials

Gain and Cardiac E-C Coupling

Revisited and Revised

Withrow Gil Wier

From the Department of Physiology, University of Maryland, Baltimore, Md.

Correspondence to Dr W. Gil Wier, Department of Physiology, University of Maryland, Baltimore, 660 West Redwood St, Baltimore, MD 21201. E-mail gwier001@umaryland.edu

See related article, pages 590–597

Key Words: unitary Calcium current • L-type Calcium channel • excitation-contraction coupling

An extract of the first 250 words of the full text is provided, because this article has no abstract.

A phenomenon that has fostered much experimental investigation and theoretical speculation is "gain" in cardiac E-C coupling. So-called "macroscopic" or "whole-cell" gain may be defined as the ratio of the total flux through the SR Ca²⁺ release channels (RyR) to that through the L-type Ca²⁺ channels (LCC). Experimentally, gain was found early on to be relatively high, and this observation, together with the seemingly incompatible fact that Ca²⁺-induced Ca²⁺ release (CICR) is normally tightly controlled in cardiac muscle, led to the development of the modern understanding of cardiac E-C coupling, the "local control" theory. Gain reflects not only the operation of the fundamental processes that underlie normal E-C coupling, but also those involved in important pathological conditions of the heart, particularly those produced by uncontrolled SR Ca²⁺ release, such as triggered arrhythmias.¹

In the heart, it can be said that "not all Ca²⁺ currents (I_Ca) are created equal"; I_Ca at negative potentials is much more efficacious in triggering SR Ca²⁺ release than is equivalent (peak) I_Ca at positive potentials. Therefore, gain decreases as activating voltage is made more positive. The conventional and widely accepted explanation of this phenomenon is based on the voltage-dependence of the single-channel (unitary) Ca²⁺ current (i_Ca), and was stated succinctly by Stern and his colleagues,² "gain decreases with voltage because the efficacy of the L-type current to trigger release from the RyR depends on the unitary current of the L-type channel, which decreases as the calcium reversal potential is approached". Indeed . . . [Full Text of this Article]

Related Article:

Voltage Dependence of Cardiac Excitation–Contraction Coupling: Unitary Ca²⁺ Current Amplitude and Open Channel Probability

Julio Altamirano and Donald M. Bers
Circ. Res. 2007 101: 590-597. [Abstract] [Full Text] [PDF]

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