Multiple transcripts of [Ca.sup.2+] channel [[alpha].sub.1]-subunits and a novel spliced variant of the [[alpha].sub.1C]-subunit in rat ductus arteriosus

Voltage-dependent [Ca.sup.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].sub.1]-subunits, [[alpha].sub.1C] and [[alpha].sub.1G] were the most predominant isoforms. Maternal administration of vitamin A significantly increased [[alpha].sub.1C] and [[alpha].sub.1G]-transcripts. Second, we examined the effect of VDCC subunits on proliferation of DA smooth muscle cells. We found that 1 [micro]M nitrendipine (an L-type [Ca.sup.2+] channel blocker) and kurtoxin (a T-type [Ca.sup.2+] channel blocker) significantly decreased [[sup.3]H]thymidine incorporation and that 3 [micro]M efonidipine (an L- and T-type [Ca.sup.2+] channel blocker) further decreased [[sup.3]H]thymidine incorporation, suggesting that L- and T-type [Ca.sup.2+] channels are involved in smooth muscle cell proliferation in the DA. Third, we found that a novel alternatively spliced variant of the [[alpha].sub.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].sub.1C]-subunit. We conclude that multiple VDCC subunits were identified in the DA, and, in particular, [[alpha].sub.1C] and [[alpha].sub.1G],-subunits were predominant in the DA. A novel spliced variant of the [[alpha].sub.1C]-subunit gene may play a distinct role in neointimal cushion formation in the DA. alternative spliced: development: gene expression: fetal circulation