Functional roles of Cav1.3(α1D) calcium channels in atria: Insights gained from gene-targeted null mutant mice

Zhao Zhang, Yuxia He, Dipika Tuteja, Danyan Xu, Valeriy Timofeyev, Qian Zhang, Kathryn A. Glatter, Yanfang Xu, Hee Sup Shin, Reginald Low, Nipavan Chiamvimonvat

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Background - Previous data suggest that L-type Ca2+ channels containing the Cav1.3(α1D) subunit are expressed mainly in neurons and neuroendocrine cells, whereas those containing the Ca v1.2(α1C) subunit are found in the brain, vascular smooth muscle, and cardiac tissue. However, our previous report as well as others have shown that Cav1.3 Ca2+ channel-deficient mice (Cav1.3-/-) demonstrate sinus bradycardia with a prolonged PR interval. In the present study, we extended our study to examine the role of the Cav1.3(α1D) Ca2+ channel in the atria of Ca-/- mice. Methods and Results - We obtained new evidence to demonstrate that there is significant expression of Cav1.3 Ca 2+ channels predominantly in the atria compared with ventricular tissues. Whole-cell L-type Ca2+ currents (ICa.L) recorded from single, isolated atrial myocytes from Cav1.3-/- mice showed a significant depolarizing shift in voltage-dependent activation. In contrast, there were no significant differences in the ICa.L recorded from ventricular myocytes from wild-type and null mutant mice. We previously documented the hyperpolarizing shift in the voltage-dependent activation of Cav1.3 compared with Cav1.2 Ca2+ channel subunits in a heterologous expression system. The lack of Cav1.3 Ca2+ channels in null mutant mice would result in a depolarizing shift in the voltage-dependent activation of ICa.L in atrial myocytes. In addition, the Cav1.3-null mutant mice showed evidence of atrial arrhythmias, with inducible atrial flutter and fibrillation. We further confirmed the isoform-specific differential expression of Cav1.3 versus Cav1.2 by in situ hybridization and immunofluorescence confocal microscopy. Conclusions - Using gene-targeted deletion of the Ca v1.3 Ca2+ channel, we established the differential distribution of Cav1.3 Ca2+ channels in atrial myocytes compared with ventricles. Our data represent the first report demonstrating important functional roles for Cav1.3 Ca2+ channel in atrial tissues.

Original languageEnglish (US)
Pages (from-to)1936-1944
Number of pages9
JournalCirculation
Volume112
Issue number13
DOIs
StatePublished - Sep 27 2005

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Keywords

  • Arrhythmias
  • Atrial fibrillation
  • Atrium
  • Calcium
  • Ion channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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