title: Dynamic local changes in sarcoplasmic reticulum calcium: physiological and pathophysiological roles.
abstract: 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."
authors.affiliation: Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA. eric.sobie@mssm.edu
authors.forename: Eric A
authors.initials: EA
authors.lastname: Sobie
authors.forename: W J
authors.initials: WJ
authors.lastname: Lederer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D002118:Calcium