Referenced in: none

Automatically associated channels: Slo1

Title: Mitochondrial oscillations and waves in cardiac myocytes: insights from computational models.

Authors: Ling Yang, Paavo Korge, James N Weiss, Zhilin Qu

Journal, date & volume: Biophys. J., 2010 Apr 21 , 98, 1428-38

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20409461

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.