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.