Conversion of monensin from an ionophore to an inhibitor of Na+ uptake by SV3t3 membrane vesicles as a function of Na+ concentration

Monensin is a Na⁺ ionophore in membrane vesicles from SV3T3 cells; but its ability to stimulate Na⁺ flux is inhibited by increasing concentrations of Na⁺. At greater than 20-mM Na⁺, monensin inhibits Na⁺ uptake by the vesicles. Cs⁺ and NH₄⁺ also cause monensin to inhibit Na⁺ uptake, but general alterations in ionic strength do not convert the ionophore to an inhibitor. Monensin does not cause Na⁺ loss during collection of the vesicles on filters; nor is inhibition the result of the vesicle lumen being made alkaline by H⁺ loss in exchange for Na⁺. The specificity for cation and ionophore indicates that a precise interaction between the cation, ionophore, and membrane is required for inhibition.