title: Pro- and antiarrhythmic effects of ATP-sensitive potassium current activation on reentry during early afterdepolarization-mediated arrhythmias.
abstract: 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.
authors.affiliation: Department of Medicine (Cardiology), David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA.
authors.forename: Marvin G
authors.initials: MG
authors.lastname: Chang
authors.forename: Enno
authors.initials: E
authors.lastname: de Lange
authors.forename: Guillaume
authors.initials: G
authors.lastname: Calmettes
authors.forename: Alan
authors.initials: A
authors.lastname: Garfinkel
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qu
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D018780:Body Surface Potential Mapping / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D020110:Pinacidil / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D016171:Torsades de Pointes / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D054086:KATP Channels; D020110:Pinacidil