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A Spatiotemporal Ventricular Myocyte Model Incorporating Mitochondrial Calcium Cycling.


ABSTRACT: Intracellular calcium (Ca2+) cycling dynamics in cardiac myocytes are spatiotemporally generated by stochastic events arising from a spatially distributed network of coupled Ca2+ release units that interact with an intertwined mitochondrial network. In this study, we developed a spatiotemporal ventricular myocyte model that integrates mitochondria-related Ca2+ cycling components into our previously developed ventricular myocyte model consisting of a three-dimensional Ca2+ release unit network. Mathematical formulations of mitochondrial membrane potential, mitochondrial Ca2+ cycling, mitochondrial permeability transition pore stochastic opening and closing, intracellular reactive oxygen species signaling, and oxidized Ca2+/calmodulin-dependent protein kinase II signaling were incorporated into the model. We then used the model to simulate the effects of mitochondrial depolarization on mitochondrial Ca2+ cycling, Ca2+ spark frequency, and Ca2+ amplitude, which agree well with experimental data. We also simulated the effects of the strength of mitochondrial Ca2+ uniporters and their spatial localization on intracellular Ca2+ cycling properties, which substantially affected diastolic and systolic Ca2+ levels in the mitochondria but exhibited only a small effect on sarcoplasmic reticulum and cytosolic Ca2+ levels under normal conditions. We show that mitochondrial depolarization can cause Ca2+ waves and Ca2+ alternans, which agrees with previous experimental observations. We propose that this new, to our knowledge, spatiotemporal ventricular myocyte model, incorporating properties of mitochondrial Ca2+ cycling and reactive-oxygen-species-dependent signaling, will be useful for investigating the effects of mitochondria on intracellular Ca2+ cycling and action potential dynamics in ventricular myocytes.

SUBMITTER: Song Z 

PROVIDER: S-EPMC6990377 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A Spatiotemporal Ventricular Myocyte Model Incorporating Mitochondrial Calcium Cycling.

Song Zhen Z   Xie Lai-Hua LH   Weiss James N JN   Qu Zhilin Z  

Biophysical journal 20190912 12


Intracellular calcium (Ca<sup>2+</sup>) cycling dynamics in cardiac myocytes are spatiotemporally generated by stochastic events arising from a spatially distributed network of coupled Ca<sup>2+</sup> release units that interact with an intertwined mitochondrial network. In this study, we developed a spatiotemporal ventricular myocyte model that integrates mitochondria-related Ca<sup>2+</sup> cycling components into our previously developed ventricular myocyte model consisting of a three-dimensi  ...[more]

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