Stretch-Induced TRPC4 Downregulation is Accompanied By Reduced Capacitative Ca2+ Entry in WKY But Not SHR Mesenteric Smooth Muscle Cells

Abstract

Our previous work showed that a 6-hour cyclic stretch significantly decreases TRPC4 protein expression and capacitative Ca2+ entry in vascular smooth muscle cells from Sprague-Dawley rats. To parallel these studies, mesenteric smooth muscle cells from spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY) rats, were subjected to stretch. TRPC4 protein expression was evaluated by Western blot and Ca2+ mobilization was measured using fura-2. As in Sprague-Dawley cells, a 6-hour stretch resulted in a significant down-regulation of TRPC4 protein in both SHR and WKY mesenteric smooth muscle cells. While WKY cells showed a stretch-induced decrease in Ca2+ dynamics to accompany the reduction in TRPC4 expression, mesenteric smooth muscle cells from SHR showed a stretch-induced increase in both the release of stored Ca2+ and capacitative Ca2+ entry. TRPC4 proteins may be working as store-operated channels in normotensive vascular smooth muscle cells and their down-regulation by stretch may be a protective mechanism to prevent additional Ca2+ influx during stretch. The stretch-induced increase in capacitative Ca2+ entry in SHR may be due to a compensatory upregulation of non-TRPC4 channels or an increase in store-operated signaling or channel activity.