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Geometric understanding of local fluctuation distribution of conduction time in lined-up cardiomyocyte network in agarose-microfabrication multi-electrode measurement assay

We examined characteristics of the propagation of conduction in width-controlled cardiomyocyte cell networks for understanding the contribution of the geometrical arrangement of cardiomyocytes for their local fluctuation distribution. We tracked a series of extracellular field potentials of linearly lined-up mouse primary cardiomyocytes and human embryonic stem cell-derived cardiomyocytes with 100 kHz sampling intervals of multi-electrodes signal acquisitions and an agarose microfabrication technology to localize the cardiomyocyte geometries in the lined-up cell networks with 100-300 µm wide agarose microstructures. Conduction time between two neighbor microelectrodes showed Gaussian distribution, which indicates this conduction propagation in a unit length was a stochastic firing phenomenon. However, the distributions of conduction time were not expanded but maintained within an identical range of distribution regardless of their propagation distances from a unit microelectrode distance, 0.3 mm, to five units of the distance, 1.5 mm, which is against the expected distance-dependent enlarging of the distribution based on the faster firing regulation. In contrast, when Quinidine was applied to the cardiomyocytes, the distributions of conduction time were expanded as propagation distance increased as predicted by the conduction propagation model of faster firing regulation. The results indicate the “faster firing regulation” is not sufficient to explain this conservation of the propagation time distribution in cardiomyocyte networks, and suggest the existence of some cooperative conduction propagation regulation, which is disappeared by the sodium channel blocking. In this meeting, we discuss the possible interpretation of this synchronous behavior more in detail and the influence of this phenomenon for diagnostics.

Keywords: on-chip cell network assay; multi microelectrode array; external field potential measurement; conduction distribution; cardiomyocyte network