Pharmacological effects on oscillatory afterpotentials in partially depolarized ventricular myocardium.
Oscillatory afterpotentials induced by toxic concentrations of ouabain were studied in isolated papillary muscles from the right ventricular myocardium of guinea pigs. In partially depolarized muscles (22 mM extracellular K+) oscillatory afterpotentials (OAP) that follow action potentials can be described as nearly harmonic, periodical damped oscillation using a five parameter model. We measured the time course of the appearance and disappearance of ouabain-induced OAP under control conditions and modified by different pharmacological tools. Changes were quantified by the parameters of the model used. Adriamycin (50 microM) significantly delayed the time to the first OAP after administration of ouabain but also shortened the time necessary for recovery after a 30 min application of ouabain. Adriamycin also reduced the damping ratio of OAP but unlike caffeine (2 mM) it did not completely suppress OAP. The reduction of the extracellular Na+ concentration from 126 to 63 mM strikingly depressed OAP both in damping ratio and amplitude. Dexamethasone (2 microM) transiently depressed already developed OAP. The effects of adriamycin as well as Na+ reduction point to a contribution of a Na/Ca exchange in the generation of OAP. The effect of dexamethasone may refer to an involvement of eicosanoides in the generation of arrhythmogenic OAP.
Albitz
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Julius Bernstein Institute of Physiology, Martin-Luther University Halle-Wittenberg, GDR, Saale.
Nilius
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B
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects*; D010042:Ouabain / Q000633:toxicity*; D010210:Papillary Muscles / Q000187:drug effects*; D012964:Sodium / Q000494:pharmacology
D010042:Ouabain; D003907:Dexamethasone; D004317:Doxorubicin; D012964:Sodium; D002118:Calcium