Pro- and antiarrhythmic effects of ATP-sensitive potassium current activation on reentry during early afterdepolarization-mediated arrhythmias

Marvin G. Chang, Enno de Lange, Guillaume Calmettes, Alan Garfinkel, Zhilin Qu, James N. Weiss

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Under conditions promoting early afterdepolarizations (EADs), ventricular tissue can become bi-excitable, that is, capable of wave propagation mediated by either the Na current (INa) or the L-type calcium current (ICa,L), raising the possibility that ICa,L-mediated reentry may contribute to polymorphic ventricular tachycardia (PVT) and torsades de pointes. ATP-sensitive K current (IKATP) activation suppresses EADs, but the effects on ICa,L-mediated reentry are unknown.To investigate the effects of IKATP activation on ICa,L-mediated reentry.We performed optical voltage mapping in cultured neonatal rat ventricular myocyte monolayers exposed to BayK8644 and isoproterenol. The effects of pharmacologically activating IKATP with pinacidil were analyzed.In 13 monolayers with anatomic ICa,L-mediated reentry around a central obstacle, pinacidil (50 ?M) converted ICa,L-mediated reentry to INa-mediated reentry. In 33 monolayers with functional ICa,L-mediated reentry (spiral waves), pinacidil terminated reentry in 17, converted reentry into more complex INa-mediated reentry resembling fibrillation in 12, and had no effect in 4. In simulated 2-dimensional bi-excitable tissue in which ICa,L- and INa-mediated wave fronts coexisted, slow IKATP activation (over minutes) reliably terminated rotors but rapid IKATP activation (over seconds) often converted ICa,L-mediated reentry to INa-mediated reentry resembling fibrillation.IKATP activation can have proarrhythmic effects on EAD-mediated arrhythmias if ICa,L-mediated reentry is present.Published by Elsevier Inc.
    Original languageEnglish
    Pages (from-to)575-582
    Number of pages8
    JournalHeart Rhythm
    Volume10
    Issue number4
    DOIs
    Publication statusPublished - 2013

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