Cardiac glycosides and intracellular Na+, K+, Ca2+.

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From the fact that cardiac glycosides exert their positive inotropy most likely via a concentration-dependent inhibition of the Na+/K+-activated ATPase, a membrane-bound enzyme regulating the intracellular potassium and sodium homeostasis, one might assume that intracellular electrolyte changes may be easily detectable. Just the opposite holds true. In the literature there are very conflicting observations depending on the experimental model, the analytical method used etc. At the moment, nevertheless, there is great body of evidence that if the cardiac glycoside inotropy is mediated by an inhibition of Na+/K+-activated ATPase this is not accompanied by a measurable alteration of intracellular ionic composition. On the other hand toxic concentrations of cardiac glycosides significantly produce a loss of cellular potassium and a rise of cellular sodium and calcium content, especially if arrhythmias are present. The increase of intracellular free and bound calcium, which manifests itself functionally as contracture, is believed to be caused at least by two mechanisms: a stimulation of the Na-Ca-exchange and an inhibition of the specific Ca2+-activated ATPase in the plasma membrane catalyzing the uphill Ca2+ outward transport. In vitro studies show that this process is impeded by a local rise of the sodium ion concentration. As the determination of myocardial ion fluxes and cellular electrolyte content has its experimental limitations, further insight may be gained by new techniques which give an answer about possible changes of the electrolyte balance at the subcellular level.