Abstract
Objective Ca2+ influx through voltage-dependent Ca2+ channels regulates vascular contraction and remodeling. However, the role of T-type Ca2+ channels (TCCs) has remained unknown in the ductus arteriosus (DA). Methods and Results 1) α1G, a major isoform of TCC in DA, was significantly up-regulated after birth. α1G was localized in the region of intimal thickening in rat perinatal DA. When the condition of culture media was changed from hypoxia (1% oxygen) to normoxia (21% oxygen), the expression of α1G mRNA was up-regulated by 1.5 fold in DA smooth muscle cells (SMCs), suggesting that the increase in oxygen tension is associated with the up-regulation of α1G mRNA in rat DA. 2) A highly selective TCC blocker, R(-)-efonidipine, significantly attenuated oxygen-induced vasoconstriction by 74% in rat DA at embryonic day 21 (p<0.01). The combination of a L-type Ca2+ channel blocker, nitrendipine, and R(-)-efonidipine induced further relaxation of DA, suggesting the additive effect of LCC and TCC. 3) DA SMC migration was increased in an extracellular Ca2+ concentration-dependent manner. DA SMC migration and proliferation were significantly decreased by stimulation of R(-)-efonidipine and by inhibition of α1G expression using α1G-specific siRNA. These data suggested that TCC promotes SMC migration and proliferation in rat DA. Conclusion TCC, which was up-regulated upon exposure to oxygen, regulated postnatal oxygen-induced DA closure through vasoconstriction and SMC migration and proliferation. [J Physiol Sci. 2007;57 Suppl:S80]
