FACTORS AND AGENTS THAT INFLUENCE CARDIAC GLYCOSIDE‐N a + , K + ‐ATP ase INTERACTION *

The optimal conditions for the binding of cardiac glycosides, such as ouabain, to Na+, K+-ATPase in vitro are the simultaneous presence of ATP, Na+ and Mg++ or the presence of inorganic phosphate (Pi) and Mg++ (Reference 1). It has been postulated that in vitro binding of ouabain in the presence of ATP, Na+ and Mg++ reflects the binding of cardiac glycosides t o this enzyme system in intact animals,2 and it is this interaction that ultimately results in the production of the positive inotropic and/or arrhythmic effects3 Thus, studies on the factors and agents that influence the cardiac glycoside-Na', K+-ATPase interaction in vitro appear important for an understanding of the factors and agents that modify the magnitude of response t o cardiac glycosides in patients when the plasma concentrations of cardiac glycosides are maintained at a fixed level Moreover, such studies may shed light on the mechanism of the Na', K+-ATPase reaction itself.