Does the colonic H,K-ATPase also act as an Na,K-ATPase?

We previously have demonstrated that the colonic P-ATPase α subunit cDNA encodes an H,K-ATPase when expressed in Xenopus laevis oocytes. Besides its high level of amino acid homology (75%) with the Na,K-ATPase, the colonic H,K-ATPase also shares a common pharmacological profile with Na,K-ATPase, because both are ouabain-sensitive and Sch 28080-insensitive. These features raise the possibility that an unrecognized property of the colonic H,K-ATPase would be Na(+) translocation. To test this hypothesis, ion-selective microelectrodes were used to measure the intracellular Na(+) activity of X. laevis oocytes expressing various combinations of P-ATPase subunits. The results show that expression in oocytes of the colonic H,K-ATPase affects intracellular Na(+) homeostasis in a way similar to the expression of the Bufo marinus Na,K-ATPase; intracellular Na(+) activity is lower in oocytes expressing the colonic H,K-ATPase or the B. marinus Na,K-ATPase than in oocytes expressing the gastric H,K-ATPase or a β subunit alone. In oocytes expressing the colonic H,K-ATPase, the decrease in intracellular Na(+) activity persists when diffusive Na(+) influx is enhanced by functional expression of the amiloride-sensitive epithelial Na(+) channel, suggesting that the decrease is related to increased active Na(+) efflux. The Na(+) decrease depends on the presence of K(+) in the external medium and is inhibited by 2 mM ouabain, a concentration that inhibits the colonic H,K-ATPase. These data are consistent with the hypothesis that the colonic H,K-ATPase may transport Na(+), acting as an (Na,H),K-ATPase. Despite its molecular and functional characterization, the physiological role of the colonic (Na,H),K-ATPase in colonic and renal ion homeostasis remains to be elucidated.