Mechanisms underlying early and delayed afterdepolarizations induced by catecholamines

S. G. Priori, P. B. Corr

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The relative influence of α- and β-adrenergic receptor activation in eliciting early (EADs) and delayed (DADs) afterdepolarizations was assessed using intracellular microelectrode recordings in isolated adult canine ventricular myocytes. Normoxic myocytes were exposed to the α-adrenergic agonist phenylephrine (10-8-10-6 M) or the β-adrenergic agonist isoproterenol (10-9-10-6 M) during pacing at different frequencies (0.5-4 Hz). α-Adrenergic stimulation resulted in a dose-dependent prolongation of action potential duration but failed to induce either EADs or DADs. β-Adrenergic stimulation with isoproterenol at low concentrations (10-9-10-8 M) induced a prolongation of the action potential, whereas higher concentrations (10-7 and 10-6 M) resulted in a marked shortening. Isoproterenol elicited single or multiple (2-5) DADs at concentrations from 10-8 to 10-6 M, with a corresponding increase in the amplitude of the DADs and decrease in the coupling interval as cells were paced at increasing rates. DADs often initiated and maintained sustained triggered rhythms that spontaneously terminated. Isoproterenol (10-8 - 10-6 M) also elicited EADs in 80% of cells at the highest concentration utilized (10-6 M) and at intermediate pacing frequencies (1-2 Hz). EADs often occurred with a 2:1 or 3:1 pattern. EADs and DADs induced by isoproterenol were reversibly abolished by low extracellular sodium, ryanodine (10-6 M), or benzamil (10-4 M), thus indicating that Ca2+ release from the sarcoplasmic reticulum and extracellular Na+ concentration are two major factors in the development of both types of afterdepolarizations. The demonstration that EADs can be induced by isoproterenol in ventricular muscle suggest a novel pathway for β-adrenergic receptors to mediate arrhythmogenesis in the intact heart.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6 27-6
Publication statusPublished - 1990


  • arrhythmias
  • calcium
  • isolated myocytes
  • triggered rhythms

ASJC Scopus subject areas

  • Physiology

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