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.
D000818:Animals; D004140:Dinitrophenols / Q000494:pharmacology*; D006329:Heart Conduction System / Q000502:physiology*; D008094:Lithium / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology*; D010138:Pacemaker, Artificial; D011188:Potassium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D012964:Sodium / Q000378:metabolism
D004140:Dinitrophenols; D010042:Ouabain; D008094:Lithium; D012964:Sodium; D011188:Potassium