Key Role of Trpc3 Channels in Calcium Homeostasis Alteration Related to No Deficiency in Aged Porcine Endothelial Cells

Abstract

NO controls the activity of canonical transient receptor potential channel (TRPC) in endothelial cells. Our group already provided evidences that reduced NO bioavailability was directly linked to increased basal cytosolic Ca2+ in a cellular model of endothelial dysfunction. The aim of this study was to evaluate the role of TRPC3 channels in Ca2+ homeostasis of aortic porcine endothelial cells (PAEC). In PAEC at P1, producing NO, specific inhibition of TRPC3 by Pyr3 induced a concentration‐dependent decrease in Ca2+ entry as shown by reduced basal [Ca2+]i and decreased Ca2+ peak amplitude in response to bradykinin. Similar modifications were observed in the presence of Orai1 inhibitor or in a Ca2+‐free buffer while OAG, a specific TRPC3 activator, didn't modify Ca2+ homeostasis. In dysfunctional PAEC at P4, model of endothelial dysfunction associated with basal increased of [Ca2+]i, Pyr3 normalized the basal [Ca2+]i in a concentration‐dependent manner while the activation of TRPC3 by OAG over increased it. These results indicate that calcium entry by TRPC3 and Orai1 channels is involved in regulation of cytosolic calcium in functional endothelial cells. In dysfunctional endothelial cells with limited NO production, an increased expression or activity of TRPC3 may participate to the abnormal Ca2+ homeostasis