TRPC Channels In Ca2+ Regulation And Endothelial Function During Cardioplegic Exposure

Abstract

Elevation of [Ca2+]i is essential to endothelial function and depolarization of endothelial membrane results in a reduction of Ca2+ influx. We studied whether canonical transient receptor potential channels (TRPC), i.e., TRPC3, is involved in [Ca2+]i dysregulation and endothelial dysfunction caused by depolarizing cardioplegia. [Ca2+]i was measured in porcine coronary endothelial cells (PCECs) and relaxation was studied in porcine small coronary arteries. Ca2+ influx and Ca2+ influx via TRPC3 were decreased in PCECs exposed to hyperkalemic solutions (10, 20 or 120 mM K+) in a concentration‐dependent manner and similar reductions occurred in cardioplegic exposure (ST, HTK or UW solution). The reduction was prevented by TRPC3/6/7 activator OAG. Hyperkalemic or cardioplegic solutions decreased EDHF‐mediated relaxation that was restored by OAG‐addition (in 20 mM K+: 52.5±4.0% vs. 67.2±4.3%; in ST: 52.2±4.8% vs. 65.0±4.8%; p<0.01). We conclude that the decrease of Ca2+ influx via TRPC3 is involved in endothelial [Ca2+]i reduction caused by depolarizing cardioplegia. TRPC activation restores Ca2+ influx and prevents EDHF impairment. This study may provide new insight for improvement of cardioplegic solutions.Supported by GRF CUHK4789/09M; CUHK2041688; China Nat'l Ministry of Sci. & Tech. 2009DFB30560 & 2010CB529502(973); Tianjin Municipal Sci. & Tech. Commission 09ZCZDSF04200 & 10JCYBJC26400.