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Subtype switching of L-Type Ca 2+ channel from Cav1.3 to Cav1.2 in embryonic murine ventricle.

Haruki Takemura, Kenji Yasui, Tobias Opthof, Noriko Niwa, Mitsuru Horiba, Atsuya Shimizu, Jong-Kook Lee, Haruo Honjo, Kaichiro Kamiya, Yuichi Ueda, Itsuo Kodama

Circ. J., 2005 Nov , 69, 1405-11

BACKGROUND: Embryonic hearts exhibit spontaneous electrical activity, which depends on Ca2+ influx through L-type Ca2+ channels. In this study the expression of the L-type Ca2+ channel alpha1 subunit gene in the developing mouse heart was investigated. METHODS AND RESULTS: Mouse cardiac ventricles 9.5 days post coitum (dpc), 18 dpc and adult were used. At 9.5 dpc the level of Cav1.3 mRNA was higher than that of Cav1.2 mRNA. With development, Cav1.2 mRNA increased and Cav1.3 mRNA decreased. Analysis of Cav1.3 splicing variants showed that Cav1.3(1b) mRNA was expressed at a higher density than Cav1.3(1a) mRNA. Cav1.3 protein was detected only at 9.5 dpc, whereas Cav1.2 protein was expressed from 9.5 dpc and its expression increased with development. L-type Ca2+ currents were prominent at 9.5 dpc. The Ca2+ current amplitude at 9.5 dpc was comparable to that at 18 dpc, and was larger in adults than at the embryonic stage. L-type Ca2+ current at 9.5 dpc was activated and/or inactivated at more negative membrane potentials than at 18 dpc or adult. L-type Ca2+ channels at 9.5 dpc were less sensitive to inhibition by nisoldipine than at adult. CONCLUSIONS: The Cav1.3 channel is functionally expressed in early embryonic mouse ventricular myocytes and potentially underlies ventricular automaticity.