A Multiwell Cardiac μGMEA Platform for Action Potential Recordings from Human iPSC-Derived Cardiomyocyte Constructs

Abstract

Summary: Multielectrode array (MEA) technology has been extensively used for field potential recordings from excitable cells. However, its application for action potential (AP) measurements has not been harnessed. Here, we report a novel platform for high-resolution intracellular AP recordings from induced pluripotent stem cell-cardiomyocyte constructs derived from human cardiac fibroblasts. To gain intracellular access, micro-gold MEAs were used to electroporate multiple constructs simultaneously. High-throughput AP measurements were obtained from 41 multicellular constructs. Repeated electroporations of the same cells did not affect the signal stability. Our model has the capability to distinguish subtle differences in AP morphology to characterize the network profile. Furthermore, we confirm the reliability of the system by recapitulating known drug-induced physiological and arrhythmogenic responses. Overall, the model provides a unique cardio-electronic interface for non-invasive measurements of AP dynamics for drug screening and disease modeling. This technology opens the door for identifying novel cardio-factors to enhance electrophysiological maturation. : Joshi-Mukherjee and colleagues introduce an alternative approach for non-invasive, long-term action potential (AP) measurements in cell networks for drug screening and disease modeling. The authors describe a novel platform for high-throughput AP recordings from the same cells over days on iPSC-cardiomyocytes constructs derived from human cardiac fibroblasts. This technology opens the door for identifying novel cardio-factors to enhance electrophysiological maturation. Keywords: human cardiac fibroblasts, iPSC-derived cardiomyocytes, multielectrode array, field potentials, action potentials, drug screening