The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

Abstract

1 The uptake of ³H-digitoxin, ³H-ouabain and ³H-dihydro-ouabain by isolated guinea-pig atria has been studied and compared with the inhibition of the sodium pump and with the inotropic effect. 2 Analysis of the curve relating the uptake of digitoxin and ouabain at equilibrium to the bath concentration enabled a non-saturable and a saturable binding site to be distinguished. 3 The uptake of inactive doses of dihydro-ouabain was only by a non-saturable mechanism. 4 The uptake of labelled digitoxin and ouabain was reduced in the presence of another glycoside. The amount of bound glycoside was nearly equivalent to the estimated non-saturable uptake. 5 The uptake was reduced at 4° C to the clearance of the non-saturable site. 6 ED50 of digitoxin and of ouabain for inhibition of the sodium pump were measured and compared to the ED50 for inotropic effect and to the concentrations producing a half-saturation of the saturable binding site. 7 It is concluded that binding to the saturable site may be responsible for the cardiac actions of the glycosides.