Novel Schering and ouabain-insensitive potassium-dependent proton secretion in the mouse cortical collecting duct
The intercalated (IC) cells of the cortical collecting duct (CCD) are important to acid-base homeostasis by secreting acid and reabsorbing bicarbonate. Acid secretion is mediated predominantly by apical membrane Schering (SCH-28080)-sensitive H+-K+- ATPase (HKA) and bafilomycin-sensitive H+-ATPase. The SCH-28080-sensitive HKA is believed to be the gastric HKA (HKAg). Here we examined apical membrane potassium-dependent proton secretion in IC cells of wild-type HKAg (+/+) and HKAg knockout (−/−) mice to determine relative contribution of HKAg to luminal proton secretion. The results demonstrated that HKAg (−/−) and wild-type mice had comparable rates of potassium-dependent proton secretion, with HKAg (−/−) mice having 100% of K+-dependent H+ secretion vs. wild-type mice. Potassium-dependent proton secretion was resistant to ouabain and SCH-28080 in HKAg knockout mice but was sensitive to SCH-28080 in wild-type animals. Northern hybridizations did not demonstrate any upregulation of colonic HKA in HKAg knockout mice. These data indicate the presence of a previously unrecognized K+-dependent SCH-28080 and ouabain-insensitive proton secretory mechanism in the cortical collecting tubule that may play an important role in acid-base homeostasis.