Intracellular Na+ overload causes oxidation of CaMKII and leads to Ca2+ mishandling in isolated ventricular myocytes

作者：Serge Viatchenko‐Karpinski, Dmytro Kornyeyev, Nesrine El‐Bizri, Grant R. Budas, Peidong Fan, Zhan Jiang, Jin Yang, Mark E. Anderson, John C. Shryock, Ching-Pin Chang, Luiz Belardinelli, Lina Yao · 发表于：Journal of Molecular and Cellular Cardiology · 年份：2014 · DOI：10.1016/j.yjmcc.2014.09.009 · 被引用次数：57 · 研究领域：Cardiac electrophysiology and arrhythmias、Ion channel regulation and function、Neuroscience and Neuropharmacology Research

An increase of late Na(+) current (INaL) in cardiac myocytes can raise the cytosolic Na(+) concentration and is associated with activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and alterations of mitochondrial metabolism and Ca(2+) handling by sarcoplasmic reticulum (SR). We tested the hypothesis that augmentation of INaL can increase mitochondrial reactive oxygen species (ROS) production and oxidation of CaMKII, resulting in spontaneous SR Ca(2+) release and increased diastolic Ca(2+) in myocytes. Increases of INaL and/or of the cytosolic Na(+) concentration led to mitochondrial ROS production and oxidation of CaMKII to cause dysregulation of Ca(2+) handling in rabbit cardiac myocytes.