These comments are directed toward the nature of the interaction between cardiotonic steroids, such as ouabain, and the red blood cell plasma membrane. I t has been known since 1953 (i) that one of the primary reactions associated with this class of steroids is their ability to inhibit the active transport of both Na and K in red cells as well as in a variety of other types of cells and tissues (2). These steroids display a very high degree of chemical specificity and act in rather low concentrations directly on the membrane. Their action on the red cell membrane is known to be asymmetric, acting only outside of the membrane (3), the side from which K is actively transported. The membrane sites to which these steroids are bound are thought to be allosteric to the transport pathway, that is, that the cardiotonic steroids act as noncompetit ive inhibitors of active transport (3). K, in addition to being actively transported, can antagonize directly the binding of these steroids to the membrane. Thus, when the concentration of inhibitor is low, K can control the rate or prevent the binding of glycosides by the membrane. I t is of interest to mention the effect of Cs. While it is known that Cs can completely replace K in activating the Na -K pump, Cs unlike K, does not appear to alter or prevent the binding of cardiac glycosides to the membrane at pump-associated sites (3). We will now consider studies concerned with direct measurements of the binding of tritiated ouabain to intact red cells and their ghosts, carried out in collaboration with Christine J, Ingram (4) and Philip B. Dunham. Our interest in these studies is to determine not only the number of
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