TRPC channels are involved in calcium‐sensing receptor mediated inhibition of renin release from Juxtaglomerular cells

Abstract

Renin containing juxtaglomerular (JG) cells express the calcium‐sensing receptor (CaSR), whose activation increases intracellular calcium (Ca). Increases in intracellular Ca decrease renin release. Canonical transient receptor potential channels (TRPC), a seven‐member subfamily of the transient receptor potential (TRP) family of ion channels, can function either as receptor‐operated or as store‐operated Ca channels, whose activation increases intracellular Ca. However, it is not known if these channels are expressed in JG cells and are involved in CaSR‐mediated regulation of renin release. We hypothesized that TRPC channels are expressed in JG cells and participate in the Ca‐mediated inhibition of renin release in response to activation of the CaSR. RT‐ PCR revealed mRNA expression of TRPC isoforms ‐1, ‐2, ‐3, ‐4, ‐5 and ‐6 in freshly isolated mouse JG cells. Incubation of primary cultures of JG cells with the TRPC blocker (SKF 96365, 50μM) did not change control values (0.46±0.09 vs. 0.46±0.08 μg ANGI/ml/hr/mg prot.) CaSR agonist cinacalcet decreased renin release by 46% to 0.25±0.05 μg ANGI/ml/hr/mg prot.(p<0.04). Addition of SKF 96365 completely reversed the CaSR‐mediated inhibition by cinacalcet. Our data suggests that JG cells contain multiple isoforms of TRPC channels, and at least one of these is linked to down‐stream signaling of CaSR‐mediated renin inhibition. (NIH 5PO1HL090550–04)