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T‐type calcium channels regulate smooth muscle cell migration, neointimal formation, and oxygen‐induced vascular contraction in rat ductus arteriosus
Author(s) -
Akaike Toru,
Yokoyama Utako,
Quan Hong,
Ishikawa Yoshihiro,
Minamisawa Susumu
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.744.7
Subject(s) - contraction (grammar) , ductus arteriosus , vascular smooth muscle , vasoconstriction , endocrinology , medicine , chemistry , agonist , receptor , fetus , anatomy , biology , smooth muscle , pregnancy , genetics
Objective Ca 2+ influx through voltage‐dependent Ca 2+ channels regulates vascular contraction and remodeling. However, the role of T‐type Ca 2+ channels (TCCs) has remained unknown in the ductus arteriosus (DA). Methods and Results 1) α1G, a TCC subtype, was significantly up‐regulated in rat neonatal DA tissues at birth and in DA smooth muscle cells (SMCs) that were exposed to oxygen. α1G was localized predominantly to the region of intimal thickening in fetal DA at term and to the central core of neonatal DA at birth. 2) α1G over expression promoted SMC migration by 164% relative to control (n=7, p <0.01). α1G‐specific siRNAs inhibited SMC migration by 60% relative to negative siRNA (n=8, p <0.01). A highly selective TCC blocker, R(−)‐efonidipine, suppressed SMC migration by 62% relative to control (n=5, p <0.01). 3) A prostaglandin E receptor EP4 agonist potently promoted physiological intimal thickening (Yokoyama et al. J Clin Invest 2006) . Intimal‐media ratio of DA stimulated by EP4 was decreased by 60% in the presence of R(−)‐efonidipine (n=5, p <0.01). 4) R(−)‐efonidipine significantly attenuated oxygen‐induced vasoconstriction in a dose‐dependent manner. Conclusion TCC, especially α1G, regulates SMC migration, neointimal formation, and oxygen‐induced vascular contraction in rat DA.