Role of TRPC1 and TRPC3 channels in constriction and relaxation of mouse thoracic aorta

Abstract

Canonical transient receptor potential (TRPC) channels expressed in smooth muscle (SMC) and endothelial cells (EC) are candidates for regulating intracellular Ca2+ and membrane potential in the vasculature. We examined the role of TRPC1 and TRPC3 channels in the mechanisms of vasocontraction and relaxation in mouse aorta.Experiments were performed with wild type (WT), TRPC1, and TRPC3 knockout (KO) mice. Contraction of aorta to phenylephrine (Phe) and relaxation to carbachol (CCh) were measured using an isometric tension bath. Intracellular Ca2+ was measured in cultured aorta EC by Fura 2. Whole cell K+ current was measured in freshly isolated SMC.Aorta from TRPC1 but not TRPC3 KO mice showed augmented contractility to Phe compared to WT. Contractions to Phe were significantly potentiated in WT (but not TRPC1) aorta in the presence of a BKCa blocker Penitrem A. In SMC, Phe‐stimulated BKCa current was reduced in TRPC1 KO compared with WT. Relaxations to CCh were significantly reduced in aorta from TRPC1 and TRPC3 KO mice. EC from TRPC1 and TRPC3 KO mice demonstrated a reduced CCh‐mediated Ca2+ response. Additionally, Ca2+ response of WT EC was attenuated by a TRPC3 blocker Pyr3.Data suggest that TRPC1 facilitates BKCa channel activation in SMC to promote attenuation of agonist‐mediated constriction. Both TRPC1 and TRPC3 contribute to endothelium‐dependent relaxation of aorta and agonist‐mediated Ca2+ influx in EC.Supported by NIH R01 HL088435 and the Intramural Research Program of the NIH, project Z01‐ES‐101684.