Dynamic local changes in sarcoplasmic reticulum calcium: Physiological and pathophysiological roles

Evidence obtained in recent years indicates that, in cardiac myocytes, release of Ca2+ from the sarcoplasmic reticulum (SR) is regulated by changes in the concentration of Ca2+ 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 [Ca2+]. We focus on five important questions that are to some extent unresolved and controversial. These questions concern: (1) the importance of SR [Ca2+] depletion in the termination of Ca2+ release; (2) the quantitative extent of depletion during local release events such as Ca2+ sparks; (3) the influence of SR [Ca2+] refilling on release refractoriness and the propensity for pathological Ca2+ release; (4) dynamic changes in SR [Ca2+] during propagating Ca2+ waves; and (5) the speed of Ca2+ 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." (C) 2011 Elsevier Ltd. All rights reserved.