Local control of Ca2+-induced Ca2+ release in mouse sinoatrial node cells

Biyi Chen, Yuejin Wu, Peter J. Mohler, Mark E. Anderson, Long Sheng Song

Research output: Contribution to journalArticle

Abstract

Emerging evidence from large animal models implicates Ca2+ regulation, particularly intracellular sarcoplasmic reticulum (SR) Ca2+ release, as essential for sinoatrial node (SAN) automaticity. However, despite the apparent importance of SR Ca2+ release to SAN cell function it is uncertain how SR Ca2+ release is controlled in SAN cells from mouse. Understanding mouse SAN SR Ca2+ release mechanism will allow improved understanding of results in studies on SAN from genetic mouse models of Ca2+ homeostatic proteins. Here we investigated the functional relationship between sarcolemmal Ca2+ influx and SR Ca2+ release at the level of single SAN cell, using simultaneous patch-clamp current recording and high resolution confocal Ca2+ imaging techniques. In mouse SAN cells, both Ca2+ channel currents and triggered SR Ca2+ transients displayed bell-shaped, graded function with the membrane potential. Moreover, the gain function for Ca2+-induced Ca2+ release (CICR) displayed a monotonically decreasing function with strong voltage dependence, consistent with a "local control" mechanism for CICR. In addition, we observed numerous discrete Ca2+ sparks at the voltage range of diastolic depolarization, in sharp contrast to the much lower frequency of sparks observed at resting potentials. We concluded that the "local control" mechanism of CICR is responsible for both local Ca2+ release during diastolic depolarization and the synchronized Ca2+ transients observed during action potential in SAN cells.

Original languageEnglish (US)
Pages (from-to)706-715
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume47
Issue number5
DOIs
StatePublished - Nov 2009
Externally publishedYes

Keywords

  • Automaticity
  • Ca sparks
  • Diastolic depolarization
  • Local control
  • Sinoatrial node

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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