Journal of Molecular and Cellular Cardiology 2014-11-01

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

Serge Viatchenko-Karpinski, Dmytro Kornyeyev, Nesrine El-Bizri, Grant Budas, Peidong Fan, Zhan Jiang, Jin Yang, Mark E Anderson, John C Shryock, Ching-Pin Chang, Luiz Belardinelli, Lina Yao

Index: J. Mol. Cell. Cardiol. 76 , 247-56, (2014)

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Abstract

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. Copyright © 2014. Published by Elsevier Ltd.