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A Computer Simulation of an Intracellular Mechanism for the Generation and Suppression of Cardiac Arrhythmias

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Abstract—This paper reports an analysis of a stochastic model of ion dynamics in the cardiac pacemaker cell within the framework of the generalized two-oscillator Maltsev–Lakatta model, including the electron-conformational model of ryanodine receptors. It has been demonstrated that generation of an action potential depends significantly on the nature of the interaction between the external membrane and the internal (Ca2+ clock) oscillators. Constructive interaction between oscillators leads to the formation of a stable action potential, while destructive interaction leads to parasitic effects, in particular, to arrhythmias. The effects of the model parameters that are characteristic of the rabbit sinoatrial heart node on the shape of the time dependence of the cell membrane potential has been investigated. The conditions under which spontaneous transition to the abnormally fast oscillatory mode takes place have been determined and the mechanism of this transition has been described; the pacemaker cell behavior in tachycardia has actually been simulated. It has been demonstrated that suppression of the rapid potassium current leads to the recovery of the normal oscillation mode of ion dynamics in a pacemaker cell, which corresponds to the mode of action of class III antiarrhythmic agents.

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Funding

This work was supported in part by the Russian Federation Government Program 211 (grant no. 02.A03.21.0006) and in part by the Ministry of Education and Science of the Russian Federation (project no. 5719).

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Authors and Affiliations

  1. Ural Federal University, 620002, Yekaterinburg, Russia

    N. M. Zorin, M. I. Shevchenko & A. S. Moskvin

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  1. N. M. Zorin
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  2. M. I. Shevchenko
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  3. A. S. Moskvin
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Corresponding author

Correspondence to M. I. Shevchenko.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors. The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by E. Martynova

Abbreviations: ML model, Maltsev–Lakatta model; EC model, electron-conformational model; RyR, ryanodine-sensitive receptor (ryanodine receptor); SP, sarcoplasmic reticulum; AP, action potential.

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Zorin, N.M., Shevchenko, M.I. & Moskvin, A.S. A Computer Simulation of an Intracellular Mechanism for the Generation and Suppression of Cardiac Arrhythmias. BIOPHYSICS 64, 639–648 (2019). https://doi.org/10.1134/S0006350919040249

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