Multiple transcripts of Ca super(2+) channel alpha sub(1)-subunits and a novel spliced variant of the alpha sub(1C)-subunit in rat ductus arteriosus

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 290; no. 4; pp. H1660 - H1670
• Main Authors: Yokoyama, U, Minamisawa, S, Adachi-Akahane, S, Akaike, T, Naguro, I, Funakoshi, K, Iwamoto, M, Nakagome, M, Uemura, N, Hori, H, Yokota, S, Ishikawa, Y
• Format: Journal Article
• Language: English
• Published: 01.04.2006
• ISSN: 0363-6135
• DOI: 10.1152/ajpheart.00100.2004

Voltage-dependent Ca super(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 mu M nitrendipine (an L-type Ca super(2+) channel blocker) and kurtoxin (a T-type Ca super(2+) channel blocker) significantly decreased [ super(3)H]thymidine incorporation and that 3 mu M efonidipine (an L- and T-type Ca super(2+) channel blocker) further decreased [ super(3)H]thymidine incorporation, suggesting that L-and T-type Ca super(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.