Dose-dependent electrophysiological effects of the myosin activator omecamtiv mecarbil in canine ventricular cardiomyocytes

N. Szentandrassy, B. Horvath, K. Vaczi, K. Kistamas, L. Masuda, J. Magyar, T. Banyasz, Z. Papp, P. P. Nanasi

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)483-489
Number of pages7
JournalJournal of Physiology and Pharmacology
Volume67
Issue number4
Publication statusPublished - Aug 2016

Keywords

  • Calcium sensitizers
  • Canine myocytes
  • Cardiac action potential
  • Cardiac ion currents
  • Myosin activators
  • Omecamtiv mecarbil

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

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