Outwards currents in embryonic stem cell-derived cardiomyocytes

The aim of the present study was to investigate the expression and function al role of outwards currents during the early stages of cardiomyogenesis. T he predominant repolarizing current in early-stage, embryonic stem (ES) cel l-derived cardiomyocytes was a 4-aminopyridine (4-AP) sensitive [concentrat ion for half-maximal inhibition (IC50) 1.7 mM], transient outward current ( I,,) with a current density of 10.3+/-2.1 pA/pF (n=72). We observed two add itional, rapidly activating, outwardly rectifying current components, I-K,I -sus and I-res, in early- and late-stage cardiomyocytes. These currents wer e characterized by slow and no inactivation, respectively, during the depol arizing voltage step. I-K,I-sus was detected in about 25% of cells investig ated and displayed 4-AP hypersensitivity (IC50 29 mu M), whereas I,,, was f ound in all cells of both differentiation stages and was 4-AP insensitive. Ln contrast to early-stage cells, I,,, formed the larger portion of the agg regate, whole-cell current in late-stage, ES cell-derived cardiomyocytes. T he current densities of all three current components increased during devel opment, 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 i n early-stage, spontaneously contracting cardiomyocytes, 4-AP depolarized t he cells, lengthened the action potential duration (APD) and increased the action potential frequency. In late-stage cells 4-AP had no effect on actio n potential frequency. We conclude that in early-stage cardiomyocytes I-to plays an important role in controlling electrical activity.