Relationship between myocardial contractility and the effects of digitalis on ionic exchange

Therapeutic concentrations of the digitalis glycosides that produce significant positive inotropy cannot be dissociated from certain effects on ionic exchange. These effects produce an increase in cellular Na and an augmentation of Ca influx. An increase of K efflux can be dissociated from the therapeutic action of the glycosides. The increase of Ca influx does not produce an increase of a component of slow inward current that is usually ascribed to transmembranous movement of Ca with voltage clamp technique. It is proposed that the primary action of the glycosides is to produce an elevation of intracellular Na--secondary to inhibition of the cellular Na-K pump. The increase of cellular Na results in augmentation of the activity of an electroneutral Na-Ca carrier system with stimulation of outward Na and inward Ca movement. The enhanced inward Ca movement is directly responsible for the positive inotropic effect of the drug.