Cell membrane receptors for cardiac glycosides in the heart

Abstract

Cell membranes contain special binding proteins for hormones and drugs. These binding sites ("receptors") located on the outside surface are linked to or are part of an enzyme facing the inner side of the membrane and are transducing and probably amplifying the information carried by the pharmacological agent to the cell. As the first step of their action cardiac glycosides reversibly bind with high affinity to specific receptors in cardiac cells and by this inhibit the (Na+ + K+)-ATPase, which is the enzyme system responsible for the active transmembraneous transport of sodium and potassium. It is thought that the inhibition of this active cation transport precedes the positive inotropic effect. Cardio-inactive glycosides have but low affinity to this receptor and thus do inhibit the (Na+ + K+)-activated ATPase only at very high concentrations. The characterization of the cardiac glycoside-receptor interaction in the heart reveals several factors that influence the affinity of the binding sites for the glycosides and thereby determine the sensitivity to this widely used group of potent drugs.