Toward an understanding of ion transport through the Na,K-ATPase.

In the Na,K-ATPase the charge-translocating reaction steps were found to be binding of the third Na(+) ion to the cytoplasmic side and the release of all three Na(+) ions to the extracellular side as well as binding of the two K(+) ions on the extracellular side. The conformation transition E(1) --> E(2) was only of minor electrogenicity; all other reaction steps produced no significant charge movements. In the SR Ca-ATPase and the gastric H,K-ATPase, all ion-binding and -release steps were identified to move charge through the membrane. The high-resolution structure of the SR Ca-ATPase in state E(1) revealed the position of the ion-binding sites in the transmembrane part of the protein. If the same arrangement is assumed for the Na pump, the missing expected charge movements in state E(1) may to be assumed to be apparent effects. With the proposal that binding of 2 Na(+) or 2 K(+) is compensated correspondingly by H(+) ions, agreement between structural and functional aspects is obtained. Investigations of the pH-dependence of ion-binding steps indicate competition between the ions and electrogenic H(+) binding in support of this concept.