Open AccessFunctional Roles of Ca v 1.3 (α 1D ) Calcium Channel in Sinoatrial Nodes
Author(s) -
Zhao Zhang,
Yancheng Xu,
Haitao Song,
Jennifer Rodriguez,
Dipika Tuteja,
Yoon Namkung,
Hee Sup Shin,
Nipavan Chiamvimonvat
Publication year - 2002
Publication title -
circulation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.899
H-Index - 336
eISSN - 1524-4571
pISSN - 0009-7330
DOI - 10.1161/01.res.0000018003.14304.e2
Subject(s) - sinoatrial node , depolarization , diastolic depolarization , chemistry , calcium , voltage dependent calcium channel , biophysics , endocrinology , medicine , biology , heart rate , blood pressure , organic chemistry
We directly examined the role of the Cav 1.3 (α1D ) Ca2+ channel in the sinoatrial (SA) node by using Cav 1.3 Ca2+ channel-deficient mice. A previous report has shown that the null mutant (Cav 1.3−/− ) 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 Cav 1.3−/− mice compared with their heterozygous (Cav 1.3+/− ) or wild-type (WT, Cav 1.3+/+ ) littermates, suggesting that the deficit is intrinsic to the SA node. Whole-cell L-type Ca2+ currents (I Ca,L s) recorded in single isolated SA node cells from Cav 1.3−/− mice show a significant depolarization shift in the activation threshold. The voltage-dependent activation of Cav 1.2 (α1C ) versus Cav 1.3 Ca2+ channel subunits was directly compared by using a heterologous expression system without β coexpression. Similar to theI Ca,L recorded in the SA node of Cav 1.3−/− mutant mice, the Cav 1.2 Ca2+ channel shows a depolarization shift in the voltage-dependent activation compared with that in the Cav 1.3 Ca2+ channel. In summary, using gene-targeted deletion of the Cav 1.3 Ca2+ channel, we were able to establish a role for Cav 1.3 Ca2+ channels in the generation of the spontaneous action potential in SA node cells.