Journal of Biological Chemistry
Volume 275, Issue 50, 15 December 2000, Pages 39193-39199
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MECHANISMS OF SIGNAL TRANSDUCTION
Functional Embryonic Cardiomyocytes after Disruption of the L-type α1C (Cav 1.2) Calcium Channel Gene in the Mouse*

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The L-type α1C(Cav1.2) calcium channel is the major calcium entry pathway in cardiac and smooth muscle. We inactivated theCav 1.2 gene in two independent mouse lines that had indistinguishable phenotypes. Homozygous knockout embryos (Cav1.2−/−) died before day 14.5 postcoitum (p.c.). At day 12.5 p.c., the embryonic heart contracted with identical frequency in wild type (+/+), heterozygous (+/−), and homozygous (−/−) Cav1.2 embryos. Beating of isolated embryonic cardiomyocytes depended on extracellular calcium and was blocked by 1 μm nisoldipine. In (+/+), (+/−), and (−/−) cardiomyocytes, an L-type Ba2+ inward current (IBa) was present that was stimulated by Bay K 8644 in all genotypes. At a holding potential of −80 mV, nisoldipine blocked IBa of day 12.5 p.c. (+/+) and (+/−) cells with two IC50 values of ≈0.1 and ≈1 μm. Inhibition of IBa of (−/−) cardiomyocytes was monophasic with an IC50 of ≈1 μm. The low affinity IBa was also present in cardiomyocytes of homozygous α1D(Cav1.3) knockout embryos at day 12.5 p.c. These results indicate that, up to day 14 p.c., contraction of murine embryonic hearts requires an unidentified, low affinity L-type like calcium channel.

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Published, JBC Papers in Press, September 5, 2000, DOI 10.1074/jbc.M006467200

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This work was supported by grants from the Deutsche Forschungsgemeinschaft, Fond zur Förderung der wissenschaftlichen Forschung Grant P12641-MED, the Östereichische Nationalbank, the VW-Stiftung, and Fond der Chemischen Industrie.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.