Colonic H+-K+-ATPase in K+conservation and electrogenic Na+ absorption during Na+ restriction

Abstract

Upregulation of the colonic H+-K+- ATPase (cHKA) during hyperaldosteronism suggests that it functions in both K+conservation and electrogenic Na+ absorption in the colon when Na+-conserving mechanisms are activated. To test this hypothesis, wild-type ( cHKA +/+) and cHKA-deficient ( cHKA −/−) mice were fed Na+-replete and Na+-restricted diets and their responses were analyzed. In both genotypes, Na+ restriction led to reduced plasma Na+ and increased serum aldosterone, and mRNAs for the epithelial Na+ channel (ENaC) β- and γ-subunits, channel-inducing factor, and cHKA were increased in distal colon. Relative to wild-type controls, cHKA −/− mice on a Na+-replete diet had elevated fecal K+ excretion. Dietary Na+restriction led to increased K+ excretion in knockout but not in wild-type mice. The amiloride-sensitive, ENaC-mediated short-circuit current in distal colon was significantly reduced in knockout mice maintained on either the Na+-replete or Na+-restricted diet. These results demonstrate that cHKA plays an important role in K+ conservation during dietary Na+ restriction and suggest that cHKA-mediated K+ recycling across the apical membrane is required for maximum electrogenic Na+ absorption.