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J Mol Cell Cardiol. 2012 Feb;52(2):304-11. doi: 10.1016/j.yjmcc.2011.06.024. Epub 2011 Jul 13.

Dynamic local changes in sarcoplasmic reticulum calcium: physiological and pathophysiological roles.

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  • 1Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA.


Evidence obtained in recent years indicates that, in cardiac myocytes, release of Ca(2+) from the sarcoplasmic reticulum (SR) is regulated by changes in the concentration of Ca(2+) within the SR. In this review, we summarize recent advances in our understanding of this regulatory role, with a particular emphasis on dynamic and local changes in SR [Ca(2+)]. We focus on five important questions that are to some extent unresolved and controversial. These questions concern: (1) the importance of SR [Ca(2+)] depletion in the termination of Ca(2+) release; (2) the quantitative extent of depletion during local release events such as Ca(2+) sparks; (3) the influence of SR [Ca(2+)] refilling on release refractoriness and the propensity for pathological Ca(2+) release; (4) dynamic changes in SR [Ca(2+)] during propagating Ca(2+) waves; and (5) the speed of Ca(2+) diffusion within the SR. With each issue, we discuss data supporting alternative viewpoints, and we identify fundamental questions that are being actively investigated. We conclude with a discussion of experimental and computational advances that will help to resolve controversies. This article is part of a special issue entitled "Local Signaling in Myocytes."

Copyright © 2011 Elsevier Ltd. All rights reserved.

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