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.