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

Upregulation of the colonic H+-K+ ATPase (cHKA) during hyperaldosteronism s uggests that it functions in both K+ conservation and electrogenic Na+ abso rption in the colon when Na+-conserving mechanisms are activated. To test t his hypothesis, wild-type (cHKA(+/+)) and cHKA-deficient (cHKA(-/-)) mice w ere fed Na+-replete and Na+-restricted diets and their responses were analy zed. In both genotypes, Na+ restriction led to reduced plasma Na+ and incre ased serum aldosterone, and mRNAs for the epithelial Na+ channel (ENaC) bet a- and gamma -subunits, channel-inducing factor, and cHKA were increased in distal colon. Relative to wild-type controls, cHKA(-/-) mice on a Na+-repl ete diet had elevated fecal K+ excretion. Dietary Na+ restriction led to in creased K+ excretion in knockout but not in wild-type mice. The amiloride-s ensitive, ENaC-mediated short-circuit current in distal colon was significa ntly reduced in knockout mice maintained on either the Na+-replete or Na+-r estricted diet. These results demonstrate that cHKA plays an important role in K+ conservation during dietary Na+ restriction and suggest that cHKA-me diated K+ recycling across the apical membrane is required for maximum elec trogenic Na+ absorption.