The function of Na⁺,K⁺-ATPase and its importance for drug action

Summary

The primary function of Na⁺,K⁺ -ATPase in cardiac and other excitable tissues is to maintain the resting, excitable state. In addition, the intracellular Ca²⁺ concentration is markedly affected by the balance between Na⁺,K⁺-ATPase activity (capacity of the sodium pump) and Na⁺ influx rate. The sodium pump in cardiac muscle has a substantial reserve capacity under normal conditions; however, a relatively modest sodium pump inhibition or an increase in Na⁺ influx rate elevates [Na⁺]_i and therefore intracellular Ca²⁺ via Na⁺/Ca²⁺ exchange. The subsequent loading of the sarcoplasmic reticulum by Cat+ and an enhanced Ca²⁺ release upon membrane excitation appear to be responsible for the positive inotropic effect of a Na⁺,K⁺-ATPase inhibitor.