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Circulation Research. 2002;90:981-987
Published online before print April 11, 2002, doi: 10.1161/01.RES.0000018003.14304.E2
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(Circulation Research. 2002;90:981.)
© 2002 American Heart Association, Inc.

Cellular Biology

Functional Roles of Cav1.3 ({alpha}1D) 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

From the Division of Cardiovascular Medicine (Z.Z., Y.X., H.S., J.R., D.T., N.C.), Department of Internal Medicine, University of California, Davis, and the National Creative Research Initiatives Center for Calcium and Learning and the Department of Life Science (Y.N., H.-S.S.), Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea.

Correspondence to Dr Nipavan Chiamvimonvat, Division of Cardiovascular Medicine, University of California, Davis, One Shields Ave, TB 172, Davis, CA 95616. E-mail nchiamvimonvat{at}ucdavis.edu

We directly examined the role of the Cav1.3 ({alpha}1D) 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 ({alpha}1C) versus Cav1.3 Ca2+ channel subunits was directly compared by using a heterologous expression system without ß 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.


Key Words: sinoatrial nodes • Cav1.3 ({alpha}1D) calcium channels




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