Subtype Switching of L-Type Ca ²⁺ Channel From Ca_v1.3 to Ca_v1.2 in Embryonic Murine Ventricle

Abstract

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 α₁ 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 Ca_v1.3 mRNA was higher than that of Ca_v1.2 mRNA. With development, Ca_v1.2 mRNA increased and Ca_v1.3 mRNA decreased. Analysis of Ca_v1.3 splicing variants showed that Ca_v1.3(1b) mRNA was expressed at a higher density than Ca_v1.3(1a) mRNA. Ca_v1.3 protein was detected only at 9.5 dpc, whereas Ca_v1.2 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 Ca_v1.3 channel is functionally expressed in early embryonic mouse ventricular myocytes and potentially underlies ventricular automaticity. (Circ J 2005; 69: 1405 - 1411)