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• W2007148145 abstract "Periodic cellwide depolarizations of mitochondrial membrane potential (PsiM) which are triggered by reactive oxygen species (ROS) and propagated by ROS-induced ROS release (RIRR) have been postulated to contribute to cardiac arrhythmogenesis and injury during ischemia/reperfusion. Two different modes of RIRR have been described: PsiM oscillations involving ROS-sensitive mitochondrial inner membrane anion channels (IMAC), and slow depolarization waves related to mitochondrial permeability transition pore (MPTP) opening. In this study, we developed a computational model of mitochondria exhibiting both IMAC-mediated RIRR and MPTP-mediated RIRR, diffusively coupled in a spatially extended network, to study the spatiotemporal dynamics of RIRR on PsiM. Our major findings are: 1), as the rate of ROS production increases, mitochondria can exhibit either oscillatory dynamics facilitated by IMAC opening, or bistable dynamics facilitated by MPTP opening; 2), in a diffusively-coupled mitochondrial network, the oscillatory dynamics of IMAC-mediated RIRR results in rapidly propagating (approximately 25 microm/s) cellwide PsiM oscillations, whereas the bistable dynamics of MPTP-mediated RIRR results in slow (0.1-2 microm/s) PsiM depolarization waves; and 3), the slow velocity of the MPTP-mediated depolarization wave is related to competition between ROS scavenging systems and ROS diffusion. Our observations provide mechanistic insights into the spatiotemporal dynamics underlying RIRR-induced PsiM oscillations and waves observed experimentally in cardiac myocytes." @default.
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• W2007148145 date "2010-04-01" @default.
• W2007148145 modified "2023-09-25" @default.
• W2007148145 title "Mitochondrial Oscillations and Waves in Cardiac Myocytes: Insights from Computational Models" @default.
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• W2007148145 doi "https://doi.org/10.1016/j.bpj.2009.12.4300" @default.
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