Activation of JG cell calcium sensing receptor inhibits renin release in part by activating different calcium channels

Abstract

We have previously shown that renin containing juxtaglomerular (JG) cells express calcium sensing receptors (CaSR). When stimulated CaSR increase intracellular calcium (Ca) and decrease renin release. However, it is not clear what the source of Ca is. We hypothesized that JG CaSR activation opens both L‐type voltage gated and/or store‐operated Ca channels (SOC). We used primary cultures of JG cells isolated from C57 mice, plated at 70‐80% confluence for 48 hrs. Control cells released renin at 0.86±0.15 ?gAngI/hr/mg prot. The CaSR agonist, sensipar, reduced renin release to 0.43±0.01 μgAngI/hr/mg prot (p<0.05), a 50% reduction. In the presence of verapamil, an L‐type channel blocker, sensipar had no effect (0.81±0.18 μgAngI/hr/mg prot (p<0.05). In different experiments, basal renin release was 0.34±0.06 μgAngI/hr/mg prot, in control cells but only 0.22±0.04 μgAngI/hr/mg prot (p<0.05) in sensipar treated cells. In the presence of BTP2, a SOC blocker, sensipar had no significant effect (0.30 ±0.05µg AngI/hr/mg prot (p<0.05).We conclude that activation of the CaSR in JG cells results in increased intracellular Ca through integrating the response of different Ca channels, resulting in a decrease in renin release.