Differential effects of extracellular cesium on early afterdepolarizations in ventricular myocytes and arrhythmogenesis in isolated hearts of rats and guinea pigs.
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 I(K1), 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(2)O(2), and the pyrethroid tefluthrin. Membrane-potential changes reversed after replacing Cs2K with Cs5K solution, with the recovery of 50% of outward I(K1). These results suggest that Cs2K solution inhibited I(K1) 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 I(K1) inhibition and EADs in ventricular myocytes are unlikely to be involved in arrhythmogenesis under our conditions.
Spencer
C Ian
CI
Division of Pulmonary and Critical Care Medicine, The Johns Hopkins Medical Institutions, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. cspencer@jhmi.edu
Borg
John J
JJ
Kozlowski
Roland Z
RZ
Sham
James S K
JS
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D002586:Cesium / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats
D002712:Chlorides; D015221:Potassium Channels; D002586:Cesium; C028019:cesium chloride