Role of TRPC1 and TRPC3 channels in contraction and relaxation of mouse thoracic aorta.

BACKGROUND/AIMS Canonical transient receptor potential (TRPC) channels modulate membrane potential and intracellular Ca(2+). We examined the role of TRPC1 and TRPC3 channels in vasocontraction and relaxation in mouse aorta. METHODS Vasocontraction and relaxation of aorta from wild-type (WT), TRPC1 KO and TRPC3 knockout (KO) mice were measured for phenylephrine (Phe) and carbachol (CCh). Intracellular Ca(2+) was measured in primary aorta endothelial cells (EC) and whole cell K(+) current in freshly isolated smooth muscle cells (SMC). RESULTS AND CONCLUSION TRPC1 KO aorta showed increased vasocontraction to Phe compared to WT and TRPC3 KO aorta due to diminished role of BK(Ca) channels. BK(Ca) mRNA (aorta) and whole cell current (SMC) were reduced versus WT. Contraction in WT aorta was increased to TRPC1 KO level by BK(Ca) channel inhibition. Relaxation to CCh was reduced in TRPC1 KO and TRPC3 KO aortas with concomitant reduction in EC Ca(2+) response. Pyr3 (TRPC3 blocker) reduced the Ca(2+) response to CCh in EC from WT, but not TRPC3 KO mice. In summary, TRPC1 attenuates receptor-mediated contraction through activation and/or expression of SMC BK(Ca) channels while TRPC3 does not contribute to receptor-mediated constriction. Both TRPC1 and TRPC3 participate in EC Ca(2+) influx and vasorelaxation of aorta.