Sinoatrial nodal cell ryanodine receptor and Na+-Ca2+ exchanger: Molecular partners in peacemaker regulation

Konstantin Y. Bogdanov, Tatiana M. Vinogradova, Edward G. Lakatta

Research output: Contribution to journalArticle

Abstract

The rate of spontaneous diastolic depolarization (DD) of sinoatrial nodal cells (SANCs) that triggers recurrent action potentials (APs) is a fundamental aspect of the heart's pacemaker. Here, in experiments on isolated SANCs, using confocal microscopy combined with a patch clamp technique, we show that ryanodine receptor Ca2+ release during the DD produces a localized subsarcolemmal Ca2+ increase that spreads in a wavelike manner by Ca2+-induced Ca2+ release and produces an inward current via the Na+-Ca2+ exchanger (NCX). Ryanodine, a blocker of the sarcoplasmic reticulum Ca2+ release channel, in a dose-dependent manner reduces the SANC beating rate with an IC50 of 2.6 μmol/L and abolishes the local Ca2+ transients that precede the AP upstroke. In voltage-clamped cells in which the DD was simulated by voltage ramp, 3 μmol/L ryanodine decreased an inward current during the voltage ramp by 1.6±0.3 pA/pF (SEM, n=4) leaving the peak of L-type Ca2+ current unchanged. Likewise, acute blockade of the NCX (via rapid substitution of bath Na+ by Li+ abolished SANC beating and reduced the inward current to a similar extent (1.7±0.4 pA/pF, n=4), as did ryanodine. Thus, in addition to activation/inactivation of multiple ion channels, Ca2+ activation of the NCX, because of localized sarcoplasmic reticulum Ca2+ release, is a critical element in a chain of molecular interactions that permits the heartbeat to occur and determines its beating rate.

Original languageEnglish (US)
Pages (from-to)1254-1258
Number of pages5
JournalCirculation research
Volume88
Issue number12
DOIs
StatePublished - Jun 22 2001
Externally publishedYes

Keywords

  • Automaticity
  • Na-Ca exchange
  • Ryanodine receptor
  • Sinoatrial node

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Sinoatrial nodal cell ryanodine receptor and Na<sup>+</sup>-Ca<sup>2+</sup> exchanger: Molecular partners in peacemaker regulation'. Together they form a unique fingerprint.

  • Cite this