Multiple transcripts of Ca2+ channel α1-subunits and a novel spliced variant of the α1C-subunit in rat ductus arteriosus

Abstract

Voltage-dependent Ca(2+) channels (VDCCs), which consist of multiple subtypes, regulate vascular tone in developing arterial smooth muscle, including the ductus arteriosus (DA). First, we examined the expression of VDCC subunits in the Wistar rat DA during development. Among alpha(1)-subunits, alpha(1C) and alpha(1G) were the most predominant isoforms. Maternal administration of vitamin A significantly increased alpha(1C)- and alpha(1G)-transcripts. Second, we examined the effect of VDCC subunits on proliferation of DA smooth muscle cells. We found that 1 microM nitrendipine (an L-type Ca(2+) channel blocker) and kurtoxin (a T-type Ca(2+) channel blocker) significantly decreased [(3)H]thymidine incorporation and that 3 microM efonidipine (an L- and T-type Ca(2+) channel blocker) further decreased [(3)H]thymidine incorporation, suggesting that L- and T-type Ca(2+) channels are involved in smooth muscle cell proliferation in the DA. Third, we found that a novel alternatively spliced variant of the alpha(1C)-isoform was highly expressed in the neointimal cushion of the DA, where proliferating and migrating smooth muscle cells are abundant. The basic channel properties of the spliced variant did not differ from those of the conventional alpha(1C)-subunit. We conclude that multiple VDCC subunits were identified in the DA, and, in particular, alpha(1C)- and alpha(1G)-subunits were predominant in the DA. A novel spliced variant of the alpha(1C)-subunit gene may play a distinct role in neointimal cushion formation in the DA.