The Na/K-ATPase: a current-generating enzyme

Given its fixed Na:K stoichiometry of 3:2 the sodium pump produces electric current and thus must be sensitive to transmembrane voltage (V-m) and have a reversal potential where current changes direction. Identification of the V-m-sensitive kinetic step(s) yields mechanistic and possibly structural information. Four such steps have been identified. A relatively large (similar to1.25 elementary charge across the membrane) outward charge translocation occurs during the Na hemicycle, ascribable to three electrogenic steps: (i) binding of the third cytoplasmic Na+ (dielectric coefficient similar to0.2), (ii) conformational change of Na deocclusion (dielectric coefficient less than or equal to0.1), and (iii) external release of sodium ions (total dielectric coefficient similar to1.0), itself composed of three sequential steps of unequal dielectric coefficient. The modest inward charge translocation (similar to0.25 elementary charge across the membrane) that takes place during the K hemicycle is completely accounted for by (iv) binding of external K+ a short distance into the membrane. Contemporary research aims to resolve the voltage-dependent kinetics and affinity for each individual intra- and extracellular Na and extracellular K ion bound or released during the pump cycle.