LOCATION AND PROPERTIES OF THE DIGITALIS RECEPTOR SITE IN NA+/K+-ATPASE

Since 1985, several research groups have shown that a number of amino acids in the catalytic α-subunit of Na+/K+-ATPase more or less strongly modulate the affinity of a digitalis compound like ouabain to the enzyme. However, scrutiny of these findings by means of chimeric Na+/K+-ATPase constructs and monoclonal antibodies has recently revealed that the modulatory effect of most of these amino acids does not at all result from direct interaction with ouabain, but rather originates from long-range effects on the properties of the digitalis binding matrix. Starting from this knowledge, the present review brings together the various pieces of evidence pointing to the conclusion that the interface between two interacting α-subunits in the Na+/K+-ATPase protodimer (αβ)2 provides the cleft for inhibitory digitalis intercalation.