Mechanism of potassium ion uptake by the Na(+)/K(+)-ATPase

The Na(+)/K(+)-ATPase restores sodium (Na(+)) and potassium (K(+)) electrochemical gradients dissipated by action potentials and ion-coupled transport processes. As ions are transported, they become transiently trapped between intracellular and extracellular gates. Once the external gate opens, three Na(+) ions are released, followed by the binding and occlusion of two K(+) ions. While the mechanisms of Na(+) release have been well characterized by the study of transient Na(+) currents, smaller and faster transient currents mediated by external K(+) have been more difficult to study. Here we show that external K(+) ions travelling to their binding sites sense only a small fraction of the electric field as they rapidly and simultaneously become occluded. Consistent with these results, molecular dynamics simulations of a pump model show a wide water-filled access channel connecting the binding site to the external solution. These results suggest a mechanism of K(+) gating different from that of Na(+) occlusion.