Russian Journal of Biological Physics and Chemisrty Russian Journal of Biological Physics and Chemisrty АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ 2499-9962 54470 Моделирование в биофизике Modelling in biophycis Моделирование в биофизике COMPUTER SIMULATION OF THE INTRACELLULAR MECHANISM OF THE CARDIAC ARRHYTHMIA CREATION AND SUPPRESSION МОДЕЛИРОВАНИЕ ВНУТРИКЛЕТОЧНОГО МЕХАНИЗМА ВОЗНИКНОВЕНИЯ И ПОДАВЛЕНИЯ СЕРДЕЧНОЙ АРИТМИИ Зорин Н М Zorin N M Шевченко М И Shevchenko M I maria.shevchenko@urfu.ru Москвин А С Moskvin A S Уральский федеральный университет им. первого Президента России Б.Н. Ельцина ru Ural Federal University, Institute of Natural Sciences and Mathematics ru Уральский федеральный университет им. первого Президента России Б.Н. Ельцина ru Ural Federal University, Institute of Natural Sciences and Mathematics ru Уральский федеральный университет им. первого Президента России Б.Н. Ельцина ru Ural Federal University, Institute of Natural Sciences and Mathematics ru 25 12 2019 25 12 2019 4 4 514 522 20 12 2019 20 12 2019 https://rusjbpc.ru/en/nauka/article/54470/view

В рамках обобщенной «двухосцилляторной» модели Мальцева-Лакатты, включающей электронно-конформационную модель рианодиновых рецепторов, рассмотрена стохастическая модель ионной динамики сердечной клетки водителя ритма. Показано, что формирование потенциала действия существенно зависит от характера взаимодействия внешнего мембранного и внутриклеточного («Ca2+-часы») осцилляторов. Конструктивное взаимодействие осцилляторов приводит к формированию устойчивого потенциала действия, тогда как деструктивное взаимодействие приводит к паразитным эффектам, в частности, аритмии. Исследовано влияние параметров модели, характерных для синоатриального узла сердца кролика, на качественный вид временной зависимости мембранного потенциала клетки. Найдены условия и описан механизм спонтанного перехода колебаний в аномально быстрый режим, тем самым фактически смоделировано поведение клетки водителя ритма при тахикардии. Показано что подавление быстрого калиевого тока нормализует колебательный режим ионной динамики клетки водителя ритма, что соответствует действию антиаритмических препаратов III класса.

We consider a stochastic model of the ion dynamics of the pacemaker's heart cell based in the generalized Maltsev-Lakatta model of two oscillators including the electron-conformational model of ryanodine receptors. It is shown that the formation of the action potential significantly depends on the nature of interactions between the external membrane and intracellular (“Ca2+ clock”) oscillators. The constructive interaction between oscillators leads to the formation of a stable action potential, while a destructive interaction leads to parasitic effects, in particular, arrhythmias. We examined the influence of the model parameters characteristic of the rabbit sinoatrial heart node on the qualitative aspect of the time dependence of the cell membrane potential. The conditions under which spontaneous transition of oscillations to the abnormally fast mode occurs have been found and this mechanism has been described, thereby the behavior of the pacemaker cell during tachycardia has actually been modeled. Computer simulation shows that the suppression of fast potassium current normalizes the oscillatory mode of the ion dynamics of the pacemaker cell, that corresponds to the action of class III antiarrhythmic drugs.

 клетка водителя ритма аритмия модель Мальцева-Лакатты электронно-конформационная модель компьютерное моделирование pacemaker cell arrhythmia Maltsev-Lakatta model electron-conformational model computer simulation Работа выполнена при поддержке Программы 211 Правительства Российской Федерации, соглашение № 02.A03.21.0006, и проекта №5719 Министерства Образования и Науки Российской Федерации.

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