Combined allosteric and competitive interaction between extracellular Na+ and K+ during ion transport by the α1, α2, and α3 isoforms of the Na, K-ATPase

A combined allosteric and competitive model describes the interaction between extracellular Na+ and Rb+ during ion transport mediated by the Na, K-ATPase. The model was developed from experiments based on Rb-86 uptake by whole cells transfected with rat isoforms of the enzyme. In the absence of Na+, only a single transport site for extracellular Rb+ exists. After the occupation of the Na+-specific allosteric site, the Rb+ transport pocket opens to allow occupation by an additional Rb+ and the subsequent transport of the two Rb+ ions into the cells. Na+ can also directly compete with Rb+ for binding to at least one of the transport sites. While the model derived here applies to each of the three rat isoforms of the Na, K-ATPase expressed in HeLa cells, subtle differences exist among the isoforms. The alpha(3)* isoform has an increased intrinsic affinity for Rb+ and a lower affinity for the allosteric Na+ site than alpha(1) or alpha(2)*. The stimulation of uptake observed according to the best-fit model is due to the displacement by Rb+ of inhibitory Na+ bound to the transport site.