Cardiac glycosides and sodium/potassium-ATPase

The sodium/potassium-ATPase complex is, according to modern research, the binding site for cardiac glycosides on the outer surface of the cell membrane and their receptor. Inhibition of this enzyme by cardiac glycosides leads for instance in the heart to a decrease or a delay in membrane sodium/potassium-ion transport, and indirectly to an increase in the intracellular ionized calcium-concentration and an increase in cardiac contractile force. According to recent observations the activity of the sodium/potassium-ATPase or its concentration, and therefore the concentration of binding sites can increase in some tissues after long term treatment with cardiac glycosides. This might explain the occasionally observed tolerance to digitalis glycosides.