Abstract
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.