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(Circulation. 1973;47:681.)
© 1973 American Heart Association, Inc.

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Mechanisms of Digitalis Toxicity

Effects of Ouabain on Phase Four of Canine Purkinje Fiber Transmembrane Potentials

MICHAEL R. ROSEN M.D.¹; HENRY GELBAND M.D.¹; CHARLES MERKER M.D.¹; BRIAN F. HOFFMAN M.D.¹

¹ From the Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York.

Microelectrode technics were used to study effects of ouabain (O), 2x10^–7 moles/liter, on phase 4 of Purkinje fiber (PF) transmembrane potentials (TMP). Perfusion for 25-35 min with O caused an increase in phase 4 depolarization which resulted in either increased automaticity or occurrence of low-amplitude potentials (LAP). Increased automaticity was more frequent when PF had been stretched, when [K⁺]_o = 2.5 mmoles/liter, and when O caused a marked decrease in resting membrane potential (RMP). LAP occurred at all [K⁺]_o (2.5, 4.0, and 5.0 mmoles/liter), and were the typical response of unstretched fibers in which RMP had not decreased markedly. The magnitude of the LAP increased at [K⁺]_o = 4.0 mmoles/liter and at faster stimulus rates. Threshold potential (TP) was decreased to a slightly greater extent than RMP. Although LAP did not result in spontaneous action potentials, superimposition of subthreshold depolarizations on LAP resulted in excitation. Whether O-induced increases in phase 4 slope result in automaticity or LAP depends on interrelationships between RMP, TP, and level of membrane potential reached during phase 4. Although hearts developing LAP due to digitalis toxicity may not demonstrate increased automaticity, the presence of phase 4 depolarization in the form of LAP may cause an impairment of conduction which is dependent on cycle length.

Key Words: Automaticity • Stimulus rates • Microelectrode studies • Low-amplitude potentials • Resting membrane potential • Threshold potential • Effects of K⁺

Submitted on October 30, 1972
Accepted on December 19, 1972

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