Arrhythmia in isolated prenatal hearts after ablation of the Cav2.3 (α1E) subunit of voltage-gated Ca2+ channels

A voltage-gated calcium channel containing Ca(v)2.3e (alpha1Ee) as the ion conducting pore has recently been detected in rat heart. Functional evidence for this Ca2+ channel to be involved in the regulation of heart beating, besides L- and T-type channels, was derived from murine embryos where the gene for Ca(v)1.2 had been ablated. The remaining,L-type like" current component was not related to recombinant splice variants of Ca(v)1.3 containing channels. As recombinant Ca(v)2.3 channels from rat were reported to be weakly dihydropyridine sensitive, the spontaneous activity of the prenatal hearts from Ca(v)2.3(-\-) mice was compared to that of Ca(v)2.3(+\+) control animals to investigate if Ca(v)2.3 could represent such a L-type like Ca2+ channel. The spontaneous activity of murine embryonic hearts was recorded by using a multielectrode array. Between day 9.5 p.c. to 12.5 p.c., the beating frequency of isolated embryonic hearts from Ca(v)2.3-deficient mice did not differ significantly from control mice but the coefficient of variation within individual episodes was more than four-fold increased in Ca(v)2.3-deficient mice indicating arrhythmia. In isolated hearts from wild type mice, arrhythmia was induced by superfusion with a solution containing 200 nM SNX-482, a blocker of some R-type voltage gated Ca2+ channels, suggesting that R-type channels containing the splice variant Ca(v)2.3e as ion conducting pore stabilize a more regular heart beat in prenatal mice. Copyright (C) 2004 S. Karger AG, Basel.