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 mutually implies 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.