Colonic [H.sup.+]-[K.sup.+]-ATPase in [K.sup.+] conservation and electrogenic [Na.sup.+] absorption during [Na.sup.+] restriction

Spicer, Zachary, Lane L. Clarke, Lara R. Gawenis, and Gary E. Shull. Colonic [H.sup.+]-[K.sup.+]-ATPase in [K.sup.+] conservation and electrogenic [Na.sup.+] absorption during [Na.sup.+] restriction. Am J Physiol Gastrointest Liver Physiol 281: G1369-G1377, 2001.--Upregulation of the colonic [H.sup.+]-[K.sup.+]-ATPase (cHKA) during hyperaldosteronism suggests that it functions in both [K.sup.+] conservation and electrogenic Na+ absorption in the colon when [Na.sup.+]-conserving mechanisms are activated. To test this hypothesis, wild-type (cHK[A.sup.+/+]) and cHKA-deficient (cHK[A.sup.-/-]) mice were fed [Na.sup.+]-replete and Na+-restricted diets and their responses were analyzed. In both genotypes, [Na.sup.+] restriction led to reduced plasma [Na.sup.+] and increased serum aldosterone, and mRNAs for the epithelial [Na.sup.+] channel (ENaC) [beta]-and [gamma]-subunits, channel-inducing factor, and cHKA were increased in distal colon. Relative to wild-type controls, cHK[A.sup.-/-] mice on a [Na.sup.+]-replete diet had elevated fecal [K.sup.+] excretion. Dietary [Na.sup.+] restriction led to increased [K.sup.+] 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.sup.+]-replete or [Na.sup.+]-restricted diet. These results demonstrate that cHKA plays an important role in [K.sup.+] conservation during dietary [Na.sup.+] restriction and suggest that cHKA-mediated [K.sup.+] recycling across the apical membrane is required for maximum electrogenic [Na.sup.+] absorption. Atp1al1; potassium absorption; sodium absorption; hydrogen secretion