Involvement of Sarcolemmal Na⁺-K⁺ ATPase in the Pathogenesis of Heart Disease

Abstract

It is now well established that Na⁺-K⁺ ATPase is primarily localized in the sarcolemmal membrane in the myocardium (1,2). This enzyme is intimately involved in the transport of Na⁺ and K⁺ and is thus considered to maintain the electrochemical gradient across the cell membrane which allows depolarization to occur. An inhibition of Na⁺-K⁺ ATPase activity has been shown to increase the intracellular concentration of Na⁺, which then increases the cytoplasmic level of Ca ²⁺ through Na ⁺-Ca ²⁺ exchange system in the plasma membrane and thus has been proposed to serve as a mechanism of the positive inotropic action of cardiac glycosides (digitalis). Although Na⁺-K⁺ ATPase is known to possess high and low affinity sites for cardiac glycosides, the exact significance of these sites is not clear at present (3). Since the intracellular concentration of Na ⁺ has been shown to regulate myocardial contractility (4), any change in the operation of sarcolemmal Na⁺-K⁺ ATPase activity can be seen to alter Ca²⁺ ion movements in the cell and thus modify the heart function. Accordingly, a great deal of attention has been focussed on elucidation of the function of this enzyme in both health and disease.