Abstract 335: Introducing a Multiwell Cardiac μGMEA Platform for Action Potential Recordings From Human iPSC Derived Cardiomyocyte Constructs

Abstract

Multielectrode array technology utilizing iPSC derived cardiomyocytes has proven useful for drug screening and arrhythmia studies. However, its application for direct action potential (AP) measurements from multicellular preparations remains limiting. We report a novel platform for high temporal resolution AP recordings from human iPSC-derived cardiomyocyte (hiPSC-CM) constructs. Derivation of high purity hiPSC-CMs yielded syncytial monolayers when cultured on a PEDOT-coated micro-gold multielectrode array (μGMEA). We gained intracellular access via 30 seconds of localized electroporation causing a revertible transition of extracellular field potential signals to quasi-APs to APs. We recorded a total of 492 AP waveforms within and across 9 constructs simultaneously and classified their morphologies based on action potential duration ratio (APD 50 /APD 90 ) and difference (APD 90 –APD 50 ). The vast majority of the waveforms (90.8%) were found to be ventricular-like with APD 50 /APD 90 and APD 90 –APD 50 of 0.75-0.95 and 52-166ms respectively. APD 30 displayed a wider variability within individual constructs when compared to the APD 80 distribution. The variability in fractional repolarization (APD 80 – APD 30 /APD 80 ) and triangulation (APD 80 – APD 30 ), parameters widely used for drug screening and arrhythmogenesis, ranged from 0.1- 0.8 and 100- 550ms respectively. The Gaussian distribution produced a single peak across these parameters confirming the ventricular-like properties of all the constructs. We confirmed the reliability of the system by recapitulating known drug induced responses on APs. Norepinephrine and isoproterenol associated with β-adrenergic stimulation produced a dose dependent increase in beating rate and shortening of APD. E4031, a hERG channel blocker, elicited a dose dependent prolongation of the APD and produced arrhythmic early afterdepolarizations (EADs) thus modulating AP waveforms via external factors. Our cardiac μGMEA model has the capability to distinguish subtle differences in AP morphology for identifying novel cardio-factors and for drug screening.