Electrophysiological and Biochemical Responses Mimic In Vivo Cells
Although purified iPSC-derived cardiomyocytes have the physical appearance of cardiomyocytes and aggregations of the cells exhibit synchronous, syncytial, contractile activity (i.e., the cells beat), it was necessary to test the cells’ electrophysiological and biochemical responses to antagonists to determine their utility for drug development and toxicity testing.
Cardiomyocyte subtypes of the heart have distinctive electrophysiological profiles that can be characterized by, among other items, early depolarization events (phase 4 depolarization) and the duration of the depolarized plateau potential. Action potentials produced by individual iCell Cardiomyocytes recapitulate the action potentials of native nodal, atrial, and ventricular cardiomyocytes.
iCell Cardiomyocytes also mimic typical in vivo responses to electrophysiological antagonists. Electrophysiological responses of cardiomyocytes were tested against exposure to E-4031 (Figure 1), a well known blocker of the human cardiac Ether-a-go-go related gene (hERG) potassium channels. Just as hERG channel block prolongs cardiac repolarization in vivo, E-4031 application prolongs, in a dose-dependent manner, the field potential duration generated by iCell Cardiomyocytes as measured on a microelectrode array platform.