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

Eric A. Sobie, W. J. Lederer

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations

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.".

Original languageEnglish
Pages (from-to)304-311
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume52
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Arrhythmia
  • Ca spark
  • Ca transient
  • Ca wave
  • Mathematical modeling
  • Triggered activity
  • Ventricular myocyte

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