Outwards currents in embryonic stem cell-derived cardiomyocytes
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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.
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