Estimation of Multiple Cardiac Cells' Action Potentials From Extracellular Field Potentials

Modern biomedical technologies use a combination of microelectrode array (MEA) systems and artificially grown cells to study disease mechanisms and test drug effects. MEA systems measure extracellular field potentials (FPs) of cell cultures or tissues, but they cannot record intracellular action potentials (APs) without some modifications or additional devices, limiting the depth of electrophysiological analysis. One of the possible solutions to the inability of MEA systems to measure APs is to mathematically reconstruct them using recorded FPs. However, accurately reconstructing APs of multiple cells is challenging task, which is complicated by many factors such as the number of cells, synchronicity of their APs, identification of their electrophysiological parameters, and noise. This paper aims to address the mathematical problem of AP synchronicity, asynchronicity and partial synchronicity between multiple cells. In this study, mathematical techniques were employed to derive a system of equations capable of reconstructing the APs of N cells simultaneously, using the FPs recorded with N + 1 electrodes. The equations take into account the number of cells, synchronicity and variation of their APs and specific electrical properties of the cells and the medium. In numerical experiments the equations were applied to reconstruct APs from FPs for cases with different types of synchronicity in noise-free and noisy conditions. The reconstructed APs, when combined with recorded FPs, expand the number of electrophysiological characteristics available for cardiotoxicity assessment in MEA systems.