期刊
CIRCULATION RESEARCH
卷 90, 期 9, 页码 981-987出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000018003.14304.E2
关键词
sinoatrial nodes; Ca(v)1.3 (alpha(1D)) calcium channels
资金
- NHLBI NIH HHS [HL-68507, R01 HL-67737] Funding Source: Medline
We directly examined the role of the Ca(v)1.3 (alpha(1D)) Ca2+ channel in the sinoatrial (SA) node by using Ca(v)1.3 Ca2+ channel-deficient mice. A previous report has shown that the null mutant (Ca(v)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 Ca(v)1.3(-/-) mice compared with their heterozygous (Ca(v)1.3(+/-)) or wild-type (WT, Ca(v)1.3(+/+)) littermates, suggesting that the deficit is intrinsic to the SA node. Whole-cell L-type Ca2+ currents (I(CaL)s) recorded in single isolated SA node cells from Ca(v)1.3(-/-) mice show a significant depolarization shift in the activation threshold. The voltage-dependent activation of Ca(v)1.2 (alpha(IC)) versus Ca(v)1.3 Ca2+ channel subunits was directly compared by using a heterologous expression system without 0 coexpression. Similar to the I-Ca.L recorded in the SA node of Ca(v)1.3(-/-) mutant mice, the Ca(v)1.2 Ca2+ channel shows a depolarization shift in the voltage-dependent activation compared with that in the Ca(v)1.3 Ca2+ channel. In summary, using gene-targeted deletion of the Ca(v)1.3 Ca2+ channel, we were able to establish a role for Ca(v)1.3 Ca2+ channels in the generation of the spontaneous action potential in SA node cells.
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