Triggered activity induced by K(+)-free, Na(+)-deficient solution in guinea pig ventricular muscle: the effects of ouabain, lidocaine, and Ca2+ channel blockers.
Triggered activity induced by delayed afterdepolarizations has been suggested as a cellular mechanism for some arrhythmias. The development of triggered activity should be favored by conditions that increase myoplasmic Ca2+ and increase membrane resistance. A solution which could create these conditions was devised. After perfusion with normal Tyrode's solution, 24 trabeculae were exposed to the experimental solution. All preparations developed triggered activity after exposure to the experimental solution, 83% developed delayed afterdepolarizations before the onset of triggered activity, and triggered activity stopped in all trabeculae after reperfusion with normal Tyrode's solution. The interaction of ouabain, lidocaine, and three Ca2+ channel blockers with triggered activity induced by the experimental solution is described. Verapamil inhibited triggered activity but not underlying voltage oscillations, whereas nisoldipine and Mn2+ inhibited both triggered activity and voltage oscillations. Lidocaine did not inhibit afterdepolarizations or triggered activity. Exposure to ouabain for 10 min caused delayed afterdepolarizations but not triggered activity. Our results show that the experimental solution induced triggered activity, which was highly reliable and readily reversible. The high reproducibility of this activity enables the study of interactions of pharmacological agents with this triggered activity. This may contribute to the further understanding of the mechanism underlying some arrhythmias.
Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona.
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Gilat
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Aronson
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Nordin
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011188:Potassium / Q000502:physiology*; D012964:Sodium / Q000172:deficiency*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D002121:Calcium Channel Blockers; D013757:Tetraethylammonium Compounds; D010042:Ouabain; D008012:Lidocaine; D012964:Sodium; D011188:Potassium