Isoproterenol is a beta-adrenergic agonist, well known for its positive inotropic effects on human cardiomyocytes. Common iPSC-derived cardiomyocyte in vitro assays fail to display this physiological response, casting doubt on the maturity of this cell model. Within the physiological mechanical environment of the FLEXcyte 96 system, positive inotropic responses of iPSC-derived cardiomyocytes can be achieved in standard, serum-containing media.
iPSC-derived cardiomyocytes display positive force-frequency-relation when cultured on the biomimetic membranes of the FLEXcyte 96 platform.
iPSC-derived cardiomyocytes show very high sensitivity to beta-adrenergic stimulation, when cultured on FLEXcyte 96 membranes mimicking cardiac tissue. Depending on the cell model, EC50 values in the 10 nM range are possible.
Upstroke and relaxation durations decrease simultaneously with increasing concentration of isoproterenol, however, the symmetry of the contraction-relaxation-cycle remains unchanged. This effect of isoproterenol differs from other positive inotropes like Calcium-channel agonist S-Bay K8644, where the plateau-phase is prolonged by the augmented Calcium influx.
The slopes of upstroke and relaxation phases increase simultaneously, confirming symmetry-preservation.