Functional roles of Cav1.3 (α1D) calcium channel in sinoatrial nodes: Insight gained using gene-targeted null mutant mice

Zhao Zhang, Yanfang Xu, Haitao Song, Jennifer Rodriguez, Dipika Tuteja, Yoon Namkung, Hee Sup Shin, Nipavan Chiamvimonvat

Research output: Contribution to journalArticle

168 Scopus citations

Abstract

We directly examined the role of the Cav1.3 (α1D) Ca2+ channel in the sinoatrial (SA) node by using Cav1.3 Ca2+ channel-deficient mice. A previous report has shown that the null mutant (Cav1.3-/-) mice have sinus bradycardia with a prolonged PR interval. In the present study, we show that spontaneous action potentials recorded from the SA nodes show a significant decrease in the beating frequency and rate of diastolic depolarization in Cav1.3-/- mice compared with their heterozygous (Cav1.3+/-) or wild-type (WT, Cav1.3+/+) littermates, suggesting that the deficit is intrinsic to the SA node. Whole-cell L-type Ca2+ currents (ICa,Ls) recorded in single isolated SA node cells from Cav1.3-/- mice show a significant depolarization shift in the activation threshold. The voltage-dependent activation of Cav1.2 (α1C) versus Cav1.3 Ca2+ channel subunits was directly compared by using a heterologous expression system without β coexpression. Similar to the ICa,L recorded in the SA node of Cav1.3-/- mutant mice, the Cav1.2 Ca2+ channel shows a depolarization shift in the voltage-dependent activation compared with that in the Cav1.3 Ca2+ channel. In summary, using gene-targeted deletion of the Cav1.3 Ca2+ channel, we were able to establish a role for Cav1.3 Ca2+ channels in the generation of the spontaneous action potential in SA node cells.

Original languageEnglish (US)
Pages (from-to)981-987
Number of pages7
JournalCirculation Research
Volume90
Issue number9
DOIs
StatePublished - May 17 2002

Keywords

  • Ca1.3 (α) calcium channels
  • Sinoatrial nodes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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