Drug-induced delayed cardiac repolarization, a recognized risk factor for pro-arrhythmia, is the single most common cause for the withdrawal of prescription drugs. The vast majority of drugs known to prolong the repolarization of the cardiac membrane preferentially inhibit the delayed rectifier current (I Kr) by binding to the hERG K+ channel. Consequently, functional in vitro assays for predicting a drug’s potential to delay cardiac repolarization typically include evaluating hERG K+ channel block in transgenic cell lines, or action potential duration assays with primary canine or rabbit Purkinje fibers. However, the predictive value of these existing assays is limited due to species differences and the lack of complex ion channel interactions in cell lines overexpressing the hERG K+ channel. Improved simulation of cardiac networks could allow for drug discovery stage testing to elucidate off-target effects, including detrimental hERG K+ channel interactions. This ability will improve drug safety screening and reduce the cost and time of drug development. A compelling approach to this issue uses assays performed on human embryonic stem cell-derived (hESC) cardiomyocytes. Cytiva Plus Cardiomyocytes are hESC-derived and exhibit the morphology and electrophysiological activity typical of human cardiomyocytes, while the Axion BioSystems MaestroTM Microelectrode Array (MEA) system provides a high throughput platform for the evaluation of extracellular field potentials. Combining these two technologies creates a robust platform for cardiotoxicity profiling.
