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.