Differential effects of extracellular cesium on early afterdepolarization in ventricular myocytes and arrhythmogenesis in isolated hearts of rats and guinea pigs

C. Ian Spencer, John J. Borg, Roland Z. Kozlowski, James S.K. Sham

Research output: Contribution to journalArticle

Abstract

CsCl has been shown to be arrhythmogenic in-vivo and to cause early afterdepolarizations (EADs) in isolated cardiac preparations, but the underlying electrophysiological mechanisms are ill-defined. To elucidate these actions further, the effects of extracellular solutions containing 3 mM CsCl and either 2 mM KCl (Cs2K solution) or 5 mM KCl (Cs5K solution) on membrane potential and ionic currents in rat and guinea-pig ventricular myocytes were compared. Cs2K solution rapidly and reversibly inhibited outward IK1, and reduced other K+ currents by about 20%. Current-clamped myocytes were rapidly hyperpolarized by this solution and action potentials were prolonged, but EADs were not observed. In contrast, EADs were triggered by E-4031, H 2O2, and the pyrethroid tefluthrin. Membrane-potential changes reversed after replacing Cs2K with Cs5K solution, with the recovery of 50% of outward IK1. These results suggest that Cs2K solution inhibited IK1 and caused a late prolongation of the action-potential duration, but the affected membrane potentials were too negative to elicit EAD mechanisms. In isolated hearts perfused with modified Tyrode's, Cs2K, and Cs5K solutions, bradycardia and arrhythmias were evoked by both CsCl-containing solutions. A comparison of such results with the effects of these solutions on myocytes suggests that IK1 inhibition and EADs in ventricular myocytes are unlikely to be involved in arrhythmogenesis under our conditions.

Original languageEnglish (US)
Pages (from-to)478-489
Number of pages12
JournalPflugers Archiv European Journal of Physiology
Volume448
Issue number5
StatePublished - Aug 1 2004

Keywords

  • Action potential duration
  • Afterdepolarizations
  • Arrhythmogenesis
  • Langendorff-perfused hearts
  • Potassium current

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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