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Am J Physiol Renal Physiol 282: F133-F143, 2002. First published August 8, 2001; doi:10.1152/ajprenal.0124.2001
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Vol. 282, Issue 1, F133-F143, January 2002

Novel Schering and ouabain-insensitive potassium-dependent proton secretion in the mouse cortical collecting duct

Snezana Petrovic1,3, Zachary Spicer2, Tracey Greeley1, Gary E Shull2, and Manoocher Soleimani1,3

Departments of 1 Medicine and 2 Molecular Genetics, Biochemistry, and Infectious Diseases, University of Cincinnati, and 3 Veterans Administration Medical Center, Cincinnati, Ohio 45267

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.

hydrogen-potassium-adenosinetriphosphatase; kidney; mouse knockout; acid-base homeostasis


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