Na+ influx and Na+-K+ pump activation during short-term exposure of cardiac myocytes to aldosterone

To examine the effect of aldosterone on sarcolemmal Na⁺ transport, we measured ouabain-sensitive electrogenic Na⁺-K⁺ pump current (I(p)) in voltage-clamped ventricular myocytes and intracellular Na⁺ activity (a(Na)/(i)) in right ventricular papillary muscles. Aldosterone (10 nM) induced an increase in both I(p) and the rate of rise of a(Na)/(i) during Na⁺-K⁺ pump blockade with the fast-acting cardiac steroid dihydro-ouabain. The aldosterone-induced increase in I(p) and rate of rise of a(Na)/(i) was eliminated by bumetanide, suggesting that aldosterone activates Na⁺ influx through the Na⁺-K⁺-2Cl^-cotransporter. To obtain independent support for this, the Na⁺, K⁺, and Cl^- concentrations in the superfusate and solution of pipettes used to voltage clamp myocytes were set at levels designed to abolish the inward electrochemical driving force for the Na⁺-K⁺-2Cl^- cotransporter. This eliminated the aldosterone-induced increase in I(p). We conclude that in vitro exposure of cardiac myocytes to aldosterone activates the Na⁺-K⁺-2Cl^- cotransporter to enhance Na⁺ influx and stimulate the Na⁺-K⁺ pump.