Extracellular access to the Na,K pump: pathway similar to ion channel

In each normal Na,K pump cycle, first three sodium and then two potassium ions are transported; in both cases, the ions become temporarily occluded in pump conformations that isolate them from internal and external solutions. A major charge movement occurs during sodium translocation and accompanies the deocclusion of sodium ions or their release to the cell exterior, or both. The nature of the charge movement was examined by measurement of the undirectional sodium-22 efflux mediated by Nai-Nao exchange (Nai and Nao are internal and external sodium ions) in voltage-clamped, internally dialyzed squid giant axons in the absence of potassium; in this way the pump activity was restricted to the sodium-translocation pathway. Although electroneutral, the Nai-Nao exchange was nevertheless voltage-sensitive: increasingly negative potentials enhanced its rate along a saturating sigmoid curve. Such voltage dependence demonstrates that the release and rebinding of external sodium is the predominant charge-moving (hence, voltage-sensitive) step, suggesting that extracellular sodium ions must reach their binding sites deep in the pump molecule through a high-field access channel. This implies that part of the pump molecule is functionally analogous to an ion channel.