title: Outwards currents in embryonic stem cell-derived cardiomyocytes.
abstract: The aim of the present study was to investigate the expression and functional role of outwards currents during the early stages of cardiomyogenesis. The predominant repolarizing current in early-stage, embryonic stem (ES) cell-derived cardiomyocytes was a 4-aminopyridine (4-AP) sensitive [concentration for half-maximal inhibition (IC50) 1.7 mM], transient outward current (Ito) with a current density of 10.3+/-2.1 pA/pF (n=72). We observed two additional, rapidly activating, outwardly rectifying current components, I(K),sus and Ires, in early- and late-stage cardiomyocytes. These currents were characterized by slow and no inactivation, respectively, during the depolarizing voltage step. I(K),sus was detected in about 25% of cells investigated and displayed 4-AP hypersensitivity (IC50 29 microM), whereas Ires was found in all cells of both differentiation stages and was 4-AP insensitive. In contrast to early-stage cells, Ires formed the larger portion of the aggregate, whole-cell current in late-stage, ES cell-derived cardiomyocytes. The current densities of all three current components increased during development, however, the most prominent increase was observed for I(res) from 3.6+/-0.8 pA/pF (n=72) to 8+/-1.1 pA/pF (n=35). In current-clamp recordings in early-stage, spontaneously contracting cardiomyocytes, 4-AP depolarized the cells, lengthened the action potential duration (APD) and increased the action potential frequency. In late-stage cells 4-AP had no effect on action potential frequency. We conclude that in early-stage cardiomyocytes I(to) plays an important role in controlling electrical activity.
authors.affiliation: Zentrum Physiologie unde Pathophysiologie, Cologne, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Gryschenko
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Lu
authors.forename: B K
authors.initials: BK
authors.lastname: Fleischmann
authors.forename: J
authors.initials: J
authors.lastname: Hescheler
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D004553:Electric Conductivity; D004594:Electrophysiology; D004622:Embryo, Mammalian / Q000502:physiology; D004625:Embryo, Nonmammalian; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology*
chemical_list: D015221:Potassium Channels; D015761:4-Aminopyridine