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

An increase of late Na+ current (I-NaL) in cardiac myocytes can raise the cytosolic Na+ concentration and is associated with activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and alterations of mitochondrial metabolism and Ca2+ 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 Ca2+ release and increased diastolic Ca2+ in myocytes. Increases of I-NaL and/or of the cytosolic Na+ concentration led to mitochondrial ROS production and oxidation of CaMKII to cause dysregulation of Ca2+ handling in rabbit cardiac myocytes. (C) 2014 The Authors. Published by Elsevier Ltd.