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Cardiovascular Research 2001 51(1):30-40; doi:10.1016/S0008-6363(01)00246-2
© 2001 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

Effects of cell-to-cell uncoupling and catecholamines on Purkinje and ventricular action potentials: implications for phase-1b arrhythmias

Arie O Verkerka,*, Marieke W Veldkampb, Ruben Coronelb, Ronald Wildersa,c and Antoni C.G van Ginnekena,b

aDepartment of Physiology, Cardiovascular Research Institute Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
bExperimental and Molecular Cardiology Group, Cardiovascular Research Institute Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
cDepartment of Medical Physiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

* Corresponding author. Academic Medical Center, Department of Physiology, Room M01-09, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Tel.: +31-20-566-4670; fax: +31-20-691-9319 a.o.verkerk{at}amc.uva.nl

Objective: The delayed phase of ventricular arrhythmias during acute ischemia (phase-1b arrhythmia) is associated with depletion of catecholamines and cell-to-cell uncoupling between depressed depolarized intramural ischemic region and surviving cells in subepicardium and subendocardium. In the present study we determined the effects of uncoupling and catecholamines on development of proarrhythmic afterdepolarizations. Methods: Depressed depolarized ischemic region was simulated by a passive electronic circuit with a potential of –73, –53, –33 or –13 mV. Using patch-clamp methodology, single sheep Purkinje and ventricular cells were coupled to the simulated ischemic region via a variable conductance. By varying coupling conductance, we were able to selectively study the effects of various degrees of uncoupling. Results: At strong coupling, cells were inexcitable and depolarized to potentials near those of the simulated ischemic region. Excitability, action potential duration and resting potential increased with progressive uncoupling. In a critical range of uncoupling, ventricular and ‘high-plateau’ Purkinje cells developed early afterdepolarizations when the potential of the simulated ischemic region was –13 mV. Norepinephrine (1 µM) frequently induced early and delayed afterdepolarizations in both ventricular and Purkinje cells, but these afterdepolarizations were only present during uncoupling when the potential of the simulated ischemic region was –33 mV or more positive. Conclusions: In a critical range of uncoupling, afterdepolarizations were present when the potential of the simulated ischemic region was –33 or –13 mV, suggesting that triggered activity plays a role in phase-1b arrhythmias when surviving layers uncouple from a highly depolarized intramural ischemic region.

KEYWORDS Adrenergic (ant)agonists; Arrhythmia (mechanisms); Cell communication; Gap junctions; Ischemia; Purkinje fiber; Ventricular arrhythmias


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