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(Circulation Research. 1999;85:770-776.)
© 1999 American Heart Association, Inc.

Reviews

Ca²⁺ Release Mechanisms, Ca²⁺ Sparks, and Local Control of Excitation-Contraction Coupling in Normal Heart Muscle

Withrow Gil Wier, C. William Balke

From the Departments of Physiology and Medicine, School of Medicine, University of Maryland, 655 W Baltimore St, Baltimore, MD, 21201.

Correspondence to Dr W. Gil Wier, Department of Physiology, University of Maryland, Baltimore, 655 W Baltimore St, Baltimore, MD 21201. E-mail gwier001@umaryland.edu

Key Words: Ca²⁺ spark • excitation-contraction coupling • L-type Ca²⁺ channel • sarcoplasmic reticulum • ryanodine receptor

	Introduction

 
It is well established that most of the Ca²⁺ that activates contraction in mammalian heart is released from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyR) and that the RyR are themselves activated by Ca²⁺ in the mechanism known as "Ca²⁺ induced Ca²⁺ release" (CICR).¹ Confocal imaging has made possible the visualization of localized Ca²⁺ release through RyR, in the form of Ca²⁺ sparks.² It appears that Ca²⁺ sparks are triggered by a local [Ca²⁺]_i,, which is different from the spatial average [Ca²⁺]_i, and which is established first in the region of the RyR by the opening of a single L-type Ca²⁺ channel.^{3 4} These phenomena are the basis of the theory of excitation-contraction (E-C) coupling known as "local control," which was predicted so presciently by Michael D. Stern in 1992.⁵ Nevertheless, the molecular mechanisms of Ca²⁺ sparks and the nature of the triggering by Ca²⁺ entry are still obscure. To complicate matters further, other possible sources of Ca²⁺ that activate, or "trigger," this release have been proposed recently, and it has even been suggested that a voltage-sensitive release mechanism, which does not require Ca²⁺, may exist in cardiac muscle, similar to that in skeletal muscle.⁶ It is our intention here to review the evidence for local control of E-C coupling in normal heart muscle and to evaluate critically the evidence for additional sources of trigger Ca²⁺ or mechanisms of SR Ca²⁺ release. We emphasize, however, that concepts about cardiac Ca²⁺ sparks, and their possible role . . . [Full Text of this Article]

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