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

BACKGROUND: 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.
OBJECTIVE: To investigate the effects of IKATP activation on ICa,L-mediated reentry.
METHODS: 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.
RESULTS: In 13 monolayers with anatomic ICa,L-mediated reentry around a central obstacle, pinacidil (50 μM) 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.
CONCLUSIONS: IKATP activation can have proarrhythmic effects on EAD-mediated arrhythmias if ICa,L-mediated reentry is present. Published by Elsevier Inc.