Na+ translocation by the cardiac Na+/K+ pump is accelerated by the cAMP-PKA pathway

Modulation of Naf pumping by the cAMP-PKA pathway was studied by means of whole-cell recording from guinea-pig ventricular myocytes dialyzed with TEA(+)-based solutions containing 5 or 50 mM Na+. Transient and steady-state pump currents were measured at 144 mM Na-o(+) and 30 degreesC. An increase of [cAMP](i) by forskolin +/- microcystin LR or by 8-bromo-cAMP resulted in a shift of the midpoint voltage (V-0.5) of the Q-V curve for transient pump currents to more negative values. The shift of V0.5 and the simultaneously occurring increase of the rate constants of current decline at positive voltages indicate a drug-induced acceleration of the transition of the El to the E2 conformation of the Na+/K+ pump. Accordingly, forskolin increased steady-state pump current of the cells to 130-140 % of control. PKA inhibitors abolished the effects of forskolin.