© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes1
aDepartment of Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center, and the Department of Veterans Affairs Medical Center 151-F, 921 NE 13th Street, Oklahoma City, OK 73104, USA
bDepartment of Experimental Cardiology, University of Leuven, Leuven, Belgium
cDepartment of Cardiology, Cardiovascular Research Institute Maastricht, University of Maastricht, P.O. Box 5800, 6202 AZ Maastricht, Netherlands
* Corresponding author. Tel. +31 43 3875101; Fax +31 43 3875104.
Objectives: This study aims at clarifying the role of cellular Ca2+ overload and spontaneous sarcoplasmic reticulum (SR) Ca2+ release in the generation of early afterdepolarizations (EAD) by isoproterenol. The involvement of a Ca2+-activated membrane current in isoproterenol-induced EAD is investigated. Methods: Membrane potential and contraction (an indicator of SR Ca2+ release) were recorded in canine left ventricular myocytes at pacing cycle lengths (CL) of 300–4000 ms. Threshold concentration for EAD was 20–50 nmol/l isoproterenol. Ni2+ (2.0–5.0 mmol/l) was used at normal and high (5.4 mmol/l) [Ca2+]o to examine the role of Ca2+ current and/or Na+–Ca2+ exchange (INa–Ca) in EAD. Results: In all cells delayed afterdepolarizations (DAD) appeared during isoproterenol. In most (
70%) cells EAD were also generated, which were fast-pacing dependent, occurring only at CL of 400–1000 ms. EAD were always initiated by a delay in repolarization. Early aftercontractions preceded the EAD upstrokes, often occurring without them. They coincided with the initial delays in repolarization. During treatment with isoproterenol, Ni2+ and high [Ca2+]o, EAD and DAD were suppressed despite the continued presence of early and delayed aftercontractions. Conclusions: Our data indicate that β-adrenergic EAD share a common ionic mechanism with DAD in terms of cellular Ca2+ overload and spontaneous SR Ca2+ release. β-Adrenergic EAD consist of two phases: (1) a conditional phase coinciding with the onset of an early aftercontraction, often followed by (2) an EAD upstroke. A Ca2+-activated membrane current, probably INa–Ca, is necessary, at least for the initiation of these EAD.
KEYWORDS Early afterdepolarizations; Delayed afterdepolarizations; Isoproterenol; Na+/Ca2+ exchange; SR Ca2+ release; Excitation–contraction coupling; Dog, ventricular myocytes
1 Part of this work was presented in abstract form: Volders PGA, Szabo B, Kulcsar A, Lazzara R. Early aftercontractions precede early afterdepolarizations induced by isoproterenol in canine ventricular myocytes. PACE Pacing Clin Electrophysiol 1995;18:831(Abstract).
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