title: Dose-dependent electrophysiological effects of the myosin activator omecamtiv mecarbil in canine ventricular cardiomyocytes.
abstract: Omecamtiv mecarbil (OM) is a myosin activator agent recently developed for treatment of heart failure. Although its action on extending systolic ejection time and increasing left ventricular ejection fraction is well documented, no data is available regarding its possible side-effects on cardiac ion channels. Therefore, the present study was designed to investigate the effects of OM on action potential morphology and the underlying ion currents in isolated canine ventricular myocytes using sharp microelectrodes, conventional patch clamp, and action potential voltage clamp techniques. OM displayed a concentration-dependent action on action potential configuration: 1 μM OM had no effect, while action potential duration and phase-1 repolarization were reduced and the plateau potential was depressed progressively at higher concentrations (10 - 100 μM; P < 0.05 compared to control). Accordingly, OM (10 μM) decreased the density of the transient outward K+current (Ito), the L-type Ca2+current (ICa) and the rapid delayed rectifier K+current (IKr), but failed to modify the inward rectifier K+current (IK1). It is concluded, that although the therapeutic concentrations of OM are not likely to influence cardiac ion currents significantly, alterations of the major cardiac ion currents can be anticipated at concentrations above those clinically tolerated.
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.|Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
authors: N
authors: N
authors: Szentandrassy
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: B
authors: B
authors: Horvath
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: K
authors: K
authors: Vaczi
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: K
authors: K
authors: Kistamas
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: L
authors: L
authors: Masuda
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.|Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: J
authors: J
authors: Magyar
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: T
authors: T
authors: Banyasz
authors: Division of Clinical Physiology, Institute of Cardiology, Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Z
authors: Z
authors: Papp
authors: Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. nanasi.peter@med.unideb.hu.|Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.
authors: P P
authors: PP
authors: Nanasi
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D005260:Female; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D009218:Myosins; D018408:Patch-Clamp Techniques; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C547293:omecamtiv mecarbil; D014508:Urea; D009218:Myosins