Ionic and electrical effects of ouabain on isolated rabbit hearts

The effects of ouabain (0.5 × 10^?6m) on the intracellular ionic concentrations and the transmembrane potential were studied. Isolated rabbit hearts were perfused at 33°C and constant coronary flow. Krebs solution containing [¹⁴C]inulin was used to measure the extracellular space (ECS). The cell Na and K content were determined after 10 and 60 min perfusion with ouabain. The membrane potential was measured throughout the experiment. Ouabain produced a decrease in ECS and cell potassium ([K]_i) and an increase in intracellular sodium ([Na]_i) and water. There was a time lag between the change in [Na]_i and the change in [K]_i. A positive inotropic effect occurred during the first 10 to 20 min of perfusion with ouabain. The resting potential (RP) and action potential amplitude (APA) decreased with a similar time course, reaching values of 63 and 55% of the control by the end of the 60 min period. The maximum rate of depolarization ($\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$) decreased after 10 min, levelling off at about 50% of the control at 30 min. An early lengthening of the plateau was followed by progressive shortening of the action potential. It is postulated that the depolarization is due to inhibition of an electrogenic ionic pump, that the changes in APA are due to ionic shifts and depolarization, and that the values of $\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ are largely determined by shifts in the h_∞ curve.