Community effect of cardiomyocytes in beating rhythms is determined by stable cells

Tatsuya Hayashi,Tetsuji Tokihiro,Kenji Yasuda,Hiroki Kurihara

doi:10.1038/s41598-017-15727-5

Tatsuya Hayashi, Tetsuji Tokihiro + Show 2 more

Open Access

https://doi.org/10.1038/s41598-017-15727-5

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Abstract

The community effect of cardiomyocytes was investigated in silico by the change in number and features of cells, as well as configurations of networks. The theoretical model was based on experimental data and accurately reproduced recently published experimental results regarding coupled cultured cardiomyocytes. We showed that the synchronised beating of two coupled cells was tuned not to the cell with a faster beating rate, but to the cell with a more stable rhythm. In a network of cardiomyocytes, a cell with low fluctuation, but not a hight frequency, became a pacemaker and stabilised the beating rhythm. Fluctuation in beating rapidly decreased with an increase in the number of cells (N), almost irrespective of the configuration of the network, and a cell comes to have natural and stable beating rhythms, even for N of approximately 10. The universality of this community effect lies in the fluctuation-dissipation theorem in statistical mechanics.

Highlights

Synchronisation of biological cycles is indispensable to life[1,2]
In the previous experiments using cultured cardiomyocytes[29], the mean beating rate and its fluctuation before and after synchronisation were observed for 14 pairs of cardiomyocytes
We applied our mathematical model of the present study to determine whether it could reproduce the results of these pairs of cardiomyocytes

Summary

Introduction

Synchronisation of biological cycles is indispensable to life[1,2]. The heartbeat is the representative phenomenon of synchronisation in physiology in which spontaneous pulsations of cardiomyocytes are tuned to a certain beating rate. They modelled a cell by the WJG model This model is expressed as fairly complex, simultaneous, differential equations in terms of the membrane potential, ion currents and ion concentrations, and its extension with stochastic processes. They showed that the time interval necessary for synchronisation is strongly dependent on the strength of cell-to-cell conductance, and it is shortened by stochastic fluctuations. Cells acquire a function of a tissue by forming a group An example of this situation is that the sinoatrial node, which generates the stable beating rhythm of the normal heart, is composed of cardiomyocytes beating autonomously. Recent experiments have shown that other cells are synchronised not to the fastest cell, but to the cell with the least fluctuation in beating rhythm[29] (Supplementary Fig. S1)

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