Abstract

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 human embryonic stem (ES) cell-derived cardiomyocytes and mouse primary 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 (300 μm) showed Gaussian distribution. However, the distributions maintained their form regardless of its propagation distances up to 1.5 mm, meaning propagation diffusion did not occur. In contrast, when Quinidine was applied, the propagation time distributions were increased as the faster firing regulation simulation predicted. The results indicate the “faster firing regulation” is not sufficient to explain the conservation of the propagation time distribution in cardiomyocyte networks but should be expanded with a kind of community effect of cell networks, such as the lower fluctuation regulation.

Highlights

  • A biological cell network is composed of a group of chemically connected or functionally associated cells

  • The results showed the conduction time distribution was maintained constant regardless of the propagation distance, which was against the conventional conduction rule “overdrive suppression” only

  • A histogram of conduction time (CT) between each electrode in the cell network was made from 5-min measurement, and a Gaussian fitting curve was made from the obtained mean time and standard deviation of time

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Summary

Introduction

A biological cell network is composed of a group of chemically connected or functionally associated cells. In contrast to neuronal networks, propagation of firing in cardiomyocytes is thought to be a homogeneous and synchronized behavior to function the heart as blood pumping. Coordinated synchronous behavior of electrical conduction among cells was explained as the faster firing regulation of heart beating [4] or is called “overdrive suppression” [5]. This conduction regulation mechanism can suppress the spontaneous beating of cells, such as Purkinje fibers, to follow the contraction impulse from the upstream sinoatrial node (SA node) with its faster beating intervals. The knowledge of length dependence of fluctuation can give us about the minimum requirement of cell-to-cell conduction length for reliable cardiotoxicity analysis and about an insight into the origin of abnormality in conductance in cellular networks

Embryonic Mouse Primary Cardiomyocytes
Human Embryonic Stem Cell-Derived Cardiomyocytes
Agarose Microfabrication
Cell Culture
Measurement System
Data Analysis
Drug Administration
Cell Staining
Statistical Analysis
Distribution of Conduction Time in Width Controlled Cardiomyocyte Networks
Correlation of Beating Intervals and Conduction Time
Correlation of Conduction Time and Its Fluctuation between Neighboring Units
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