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

doi:10.1016/j.yjmcc.2009.07.007

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

Journal article

Peer reviewed

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

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

Journal of molecular and cellular cardiology, Vol.47(5), pp.706-715

11/2009

DOI: 10.1016/j.yjmcc.2009.07.007

PMCID: PMC2761520

PMID: 19615376

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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.

Automaticity

Diastolic depolarization

Ca2+ sparks

Local control

Sinoatrial node

Details

Title: Subtitle: Local control of Ca2+-induced Ca2+ release in mouse sinoatrial node cells
Creators: Biyi Chen - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, 285 Newton Road, Iowa City, IA 52242, USA
Yuejin Wu - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, 285 Newton Road, Iowa City, IA 52242, USA
Peter J Mohler - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, 285 Newton Road, Iowa City, IA 52242, USA
Mark E Anderson - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, 285 Newton Road, Iowa City, IA 52242, USA
Long-Sheng Song - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, 285 Newton Road, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Journal of molecular and cellular cardiology, Vol.47(5), pp.706-715
DOI: 10.1016/j.yjmcc.2009.07.007
PMID: 19615376
PMCID: PMC2761520
NLM abbreviation: J Mol Cell Cardiol
ISSN: 0022-2828
eISSN: 1095-8584
Publisher: Elsevier Ltd
Language: English
Date published: 11/2009
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984094876902771

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