Adenylyl cyclase VI is necessary for AVP stimulation of ENaC

Abstract

Vasopressin is an important physiological modulator of renal sodium excretion, which is fine‐tuned in the collecting duct. This action of vasopressin is mediated in part by adenylyl cyclase‐stimulated cAMP regulation of the epithelial Na+ channel (ENaC). Multiple adenylyl cyclase isoforms are expressed in the collecting duct. The adenylyl cyclase isoform that is most important to vasopressin‐regulation of ENaC in the collecting duct is obscure. To assess this, the basal activity of ENaC and the response of this channel to desmopressin and water‐deprivation were compared in wild type mice and mice having collecting duct principal cell‐specific knockout of adenylyl cyclase type VI. Patch clamp analysis of split‐open cortical collecting ducts revealed no difference in basal ENaC activity; however, the stimulatory effects of water‐deprivation and desmopressin on ENaC were absent in knockout mice. These results demonstrate that adenylyl cyclase type VI is necessary for vasopressin stimulation of ENaC in the collecting duct but that this isoform is not necessary for basal channel activity under normal conditions.