Diastolic Calcium Release Controls the Beating Rate of Rabbit Sinoatrial Node Cells: Numerical Modeling of the Coupling Process

Victor A. Maltsev, Tatiana M. Vinogradova, Konstantin Y. Bogdanov, Edward G. Lakatta, Michael D. Stern

Research output: Contribution to journalArticle

Abstract

Recent studies employing Ca2+ indicators and confocal microscopy demonstrate substantial local Ca2+ release beneath the cell plasma membrane (subspace) of sinoatrial node cells (SANCs) occurring during diastolic depolarization. Pharmacological and biophysical experiments have suggested that the released Ca2+ interacts with the plasma membrane via the ion current (/NaCa) produced by the Na +/Ca2+ exchanger and constitutes an important determinant of the pacemaker rate. This study provides a numerical validation of the functional importance of diastolic Ca2+ release for rate control. The subspace Ca2+ signals in rabbit SANCs were measured by laser confocal microscopy, averaged, and calibrated. The time course of the subspace [Ca2+] displayed both diastolic and systolic components. The diastolic component was mainly due to the local Ca2+ releases; it was numerically approximated and incorporated into a SANC cellular electrophysiology model. The model predicts that the diastolic Ca2+ release strongly interacts with plasma membrane via /NaCa and thus controls the phase of the action potential upstroke and ultimately the final action potential rate.

Original languageEnglish (US)
Pages (from-to)2596-2605
Number of pages10
JournalBiophysical journal
Volume86
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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