The Effect of Ouabain, Dinitrophenol, and Lithium on the Pacemaker Current in Sheep Cardiac Purkinje Fibers

• Published in: Circulation research Vol. 40; no. 5; pp. 517 - 524
• Main Authors: ARONSON, RONALD S, GELLES, JEREMIAH M
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.05.1977
• Subjects: Animals; Dinitrophenols - pharmacology; Heart Conduction System - physiology; Lithium - pharmacology; Membrane Potentials - drug effects; Ouabain - pharmacology; Pacemaker, Artificial; Potassium - metabolism; Purkinje Fibers - drug effects; Purkinje Fibers - physiology; Sheep; Sodium - metabolism
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.40.5.517

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 × 107 M) caused an apparent decrease in the amplitude of the IK2activation curve. We also found that a similar effect was caused by exposure to dinitrophenol (DNP) or lithium-substituted Tyrodeʼs 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