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Articles in PresS, published online ahead of print August 8, 2001
Am J Physiol Renal Physiol, 10.1152/ajprenal.0124.2001
Submitted on April 18, 2001
Accepted on July 30, 2001
1 Internal Medicine, University of Cincinnati, Cincinnati, OH, USA
2 Molecular Genetics, Biochemistry and Infectious Diseases, University of Cincinnati, Cincinnati, OH, USA
3 Internal Medicine, University of Cincinnati, Cincinnati, OH, USA; Medicine, Veterans Administration, Cincinnati, OH, USA
* To whom correspondence should be addressed. E-mail: manoocher.soleimani{at}uc.edu.
The intercalated (IC) cells of 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 H+/K+ ATPase (HKA) is believed to be the gastric K+/H+ ATPase (HKAg). Here we examined apical membrane potassium-dependent proton secretion in IC cells of wild type HKAg (+/+) and HKAg knock out (-/-) 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 knock out mice but was sensitive to SCH 28080 in wild type animals. Northern hybridizations did not demonstrate any upregulation of colonic HKA in HKAg knock out 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.
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