کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8474511 | 1550427 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mitochondrial instability during regional ischemia-reperfusion underlies arrhythmias in monolayers of cardiomyocytes
ترجمه فارسی عنوان
بی ثباتی میتوکندریای در حین ایسکمی- رپرفیوژن منطقه ای، آریتمی ها را در تک سلول های قلبی عروقی
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کلمات کلیدی
ایسکمی مجدد متابولیسم انرژی، آریتمی های بطنی، فیبریلاسیون، میتوکندریا، بنزودیازپین،
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
چکیده انگلیسی
Regional depolarization of the mitochondrial network can alter cellular electrical excitability and increase the propensity for reentry, in part, through the opening of sarcolemmal KATP channels. Mitochondrial inner membrane potential (ÎΨm) instability or oscillation can be induced in myocytes by exposure to reactive oxygen species (ROS), laser excitation, or glutathione depletion, and is thought to be a major factor in arrhythmogenesis during ischemia-reperfusion. Nevertheless, the correlation between ÎΨm recovery kinetics and reperfusion-induced arrhythmias has been difficult to demonstrate experimentally. Here, we investigate the relationship between subcellular changes in ÎΨm, cellular glutathione redox potential, electrical excitability, and wave propagation during coverslip-induced ischemia-reperfusion (IR) in neonatal rat ventricular myocyte (NRVM) monolayers. Ischemia led to decreased action potential amplitude and duration followed by electrical inexcitability after ~ 15 min of ischemia. ÎΨm depolarization occurred in two phases during ischemia: in phase 1 (< 30 min ischemia), mitochondrial clusters within individual NRVMs depolarized, while phase 2 ÎΨm depolarization (30-60 min) was characterized by global functional collapse of the mitochondrial network across the whole ischemic region of the monolayer, typically involving a propagating metabolic wave. Oxidation of the glutathione (GSSG:GSH) redox potential occurred during ischemia, followed by recovery upon reperfusion (i.e., lifting the coverslip). ÎΨm recovered in the mitochondria of individual myocytes quite rapidly upon reperfusion (< 5 min), but was highly unstable, characterized by subcellular oscillations or flickering of clusters of mitochondria in NRVMs across the reperfused region. Electrical excitability also recovered in a heterogeneous manner, providing an arrhythmogenic substrate which led to formation of sustained reentry. Treatment with 4â²-chlorodiazepam, a peripheral benzodiazepine receptor ligand, prevented ÎΨm oscillation, improved GSH recovery rate, and prevented reentry during reperfusion, indicating that stabilization of mitochondrial network dynamics is important for preventing post-ischemic arrhythmias. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 78, January 2015, Pages 90-99
Journal: Journal of Molecular and Cellular Cardiology - Volume 78, January 2015, Pages 90-99
نویسندگان
Soroosh Solhjoo, Brian O'Rourke,