The effect of ouabain, dinitrophenol, and lithium on the pacemaker current in sheep cardiac Purkinje fibers.

We studied the effect of ouabain and other inhibitors of the Na-K pump on the pacemaker current (IK2) in sheep cardiac Purkinje fibers. We found that exposure to ouabain (2 X 10(7) M) caused an apparent decrease in the amplitude of the IK2 activation curve. We also found that a similar effect was caused by exposure to dinitrophenol (DNP) or lithium-substituted Tyrode's solution. Our studies showed that after prolonged (more than 60 minutes) exposure to ouabain a characteristic current noise appeared and IK2 was replaced by an oscillatory inward current (IOS). The apparent threshold for IOS was -50 to -60 mV and the peak amplitude of this current increased with increasing levels of depolarization positive to threshold. These results suggest that (1) the apparent decrease in IK2 may be a consequence of ionic redistribution due to Na-K pump inhibition; (2) cardiac glycosides cause abnormal impulse generation by an ionic mechanism separate from IK2 and involving IOS.