Interpretation of field and LEAP potentials recorded from cardiomyocyte monolayers

Multi-electrode arrays (MEA) are the method of choice for electrophysiological characterization of cardiomyocyte monolayers. The field potentials recorded using a MEA are like extracellular electrograms recorded from myocardium using conventional electrodes. Nevertheless, different criteria are used to interpret field potential and extracellular electrogram, which hampers correct interpretation and translation to the patient. To validate criteria for interpretation of field potentials, we used neonatal rat cardiomyocytes to generate monolayers. We recorded field potentials using a MEA and simultaneously recorded action potentials using sharp micro-electrodes. In parallel, we recreated our experimental setting in silico and performed simulations. We show that the amplitude of the local RS-complex of a field potential correlated with conduction velocity in silico but not in vitro. The peak time of the T-wave field potentials exhibited a strong correlation with APD90, while the steepest upslope correlated well with APD50. However, this relationship only holds when the T-wave displayed a biphasic pattern. Next, we simulated local extracellular action potentials (LEAP). The shape of the LEAP differed markedly from the shape of the local action potential, but the final duration of LEAP coincided with APD90. Criteria for interpretation of extracellular electrograms should be applied to field potentials. This will provide a strong basis for the analysis of heterogeneity in conduction velocity and repolarization in cultured monolayers of cardiomyocytes. Finally, a LEAP is not a recording of the local action potential but is generated by intracellular current provided by neighboring cardiomyocytes and is superior to field potential duration in estimating APD90.