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Pflügers Archiv

, Volume 439, Issue 6, pp 798–807 | Cite as

Outwards currents in embryonic stem cell-derived cardiomyocytes

  • O. Gryshchenko
  • Z.J. Lu
  • B.K. Fleischmann
  • J. Hescheler
Original Article

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 (I to) 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 I res, 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 µM), whereas I res was found in all cells of both differentiation stages and was 4-AP insensitive. In contrast to early-stage cells, I res 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.

ES cell-derived cardiomyocytes Embryoid body Early- and late-stage cardiomyocytes Outward-rectifier currents Ito Membrane potential regulation 

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • O. Gryshchenko
    • 1
  • Z.J. Lu
    • 1
  • B.K. Fleischmann
    • 1
  • J. Hescheler
    • 1
  1. 1.Zentrum Physiologie und Pathophysiologie der Universität zu Köln, Institut für Neurophysiologie, Robert-Koch-Strasse 39, D-50931 CologneGermany

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