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Am J Physiol Heart Circ Physiol (November 4, 2005). doi:10.1152/ajpheart.00100.2004
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Submitted on February 3, 2004
Accepted on October 27, 2005

Multiple transcripts of Ca2+ channel {alpha}1 subunits and a novel spliced variant of {alpha}1C subunit in the rat ductus arteriosus

Utako Yokoyama1, Susumu Minamisawa2*, Satomi Adachi-Akahane3, Toru Akaike4, Isao Naguro5, Kengo Funakoshi6, Mari Iwamoto4, Masamichi Nakagome7, Nobuyuki Uemura7, Hideaki Hori7, Shumpei Yokota4, and Yoshihiro Ishikawa8

1 Department of Physiology, Yokohama City University, Yokohama, Japan; Department of Pediatrics, Yokohama City University, Yokohama, Japan
2 Department of Physiology, Yokohama City University, Yokohama, Japan; Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan
3 Department of Pharmacology, Toho University School of Medicine, Tokyo, Japan
4 Department of Pediatrics, Yokohama City University, Yokohama, Japan
5 Laboratory of Cell Signaling, The University of Tokyo Graduate School of Pharmaceutical Sciences, Tokyo, Japan
6 Department of Neuroanatomy, Yokohama City University, Yokohama, Japan
7 Department of Physiology, Yokohama City University, Yokohama, Japan
8 Department of Physiology, Yokohama City University, Yokohama, Japan; Cardiovascular Research Institute, New Jersey Medical School, Newark, NJ 07103, USA

* To whom correspondence should be addressed. E-mail: sminamis{at}med.yokohama-cu.ac.jp.

Voltage-dependent Ca2+ 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 both {alpha}1C and {alpha}1G transcripts. Second, we examined the effect of VDCC subunits on proliferation of DA smooth muscle cells. We found that 1µM of nitrendipine (a L-type Ca2+ channel blocker) and kurtoxin (a T-type Ca2+ channel blocker) significantly decreased [3H] thymidine incorporation and 3 µM of efinidipine (a L-type and T-type Ca2+ channel blocker) further decreased [3H] thymidine incorporation, suggesting that both L-type and T-type Ca2+ channels 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 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 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 {alpha}1C gene may play a distinct role in neointimal cushion formation in the DA.




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