Sodium acts as a potassium analog on gastric H,K-ATPase.

The effects of Na+ on gastric H,K-ATPase were investigated using leaky and ion-tight H,K-ATPase vesicles. Na+ activated the total ATPase activity in the absence of K+, reaching levels of 15% relative to those in the presence of K+. The Na+ activation, which takes place at the luminal side of the membrane, depended on the ATP concentration and the type of buffer used. The steady-state ATP phosphorylation level, studied with leaky vesicles, was reduced by Na+ due to both activation of the dephosphorylation reaction and a shift to E2 in the E1<==>E2 equilibrium. By studying this equilibrium in ion-tight H,K-ATPase vesicles, it was found that Na+ drives the enzyme via a cytosolic site to the nonphosphorylating E2 conformation. No H(+)-like properties of cytosolic Na+ could be detected. We therefore conclude that Na+ behaves like K+ rather than like H+ in the H,K-ATPase reaction.