Kinetic contribution to extracellular Na + /K + selectivity in the Na + /K + pump.

The sodium potassium pump (Na+ ,K+ -ATPase) shows a high selectivity for K+ over Na+ binding from the extracellular medium. To understand the K+ selectivity in the presence of a high concentration of competing Na+ ions requires consideration of more than just ion binding affinities. Here, equilibrium-based calculations of the extracellular occupation of the Na+ ,K+ -ATPase transport sites by Na+ and K+ are compared to fluxes through Na+ and K+ transport pathways. The results show that, under physiological conditions, there is a 332-fold selectivity for pumping of K+ from the extracellular medium into the cytoplasm relative to Na+ , whereas equilibrium calculations alone predict only a 7.5-fold selectivity for K+ . Thus, kinetic effects make a major contribution to the determination of extracellular K+ selectivity.