Drug-induced changes in the superficially located stores of calcium in heart sarcolemma.

Excitation-contraction coupling in heart muscle cells depends upon an inward displacement of Ca2+ from the extra- to the intracellular phase. Some of the Ca2+ which is displaced inwards is probably derived from superficially located binding sites. Drugs which increase the peak tension developed during contraction, e.g., catecholamines and the cardiac glycosides, may act by increasing the amount of Ca2+ which becomes available for participation in the events associated with excitation-contraction coupling. The catecholamines increase in the amount of Ca2+ which is displaced inward from the extracellular phase, whereas the cardiac glycosides apparently act by increasing the exchangeability of the Ca2+ which is stored at binding sites located at the plasma membrane. Other drugs, e.g., verapamil, act in the reverse manner, decreasing the amount of Ca2+ which is available for displacement from the superficially located binding sites. These observations will be discussed in terms of an hypothesis that the plasma membrane represents an important site of drug action, and that many drugs which alter the contractile performance of the heart do so because of their ability to modify the ability of the plasma membrane to accumulate and exchange Ca2+.