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Browsing by Author "Viatchenko-Karpinski, Serge"
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Item Intracellular Na+ overload causes oxidation of CaMKII and leads to Ca2+ mishandling in isolated ventricular myocytes(Elsevier, 2014-11) Viatchenko-Karpinski, Serge; Kornyeyev, Dmytro; El-Bizri, Nesrine; Budas, Grant; Fan, Peidong; Jiang, Zhan; Yang, Jin; Anderson, Mark E.; Shryock, John C.; Chang, Ching-Pin; Belardinelli, Luiz; Yao, Lina; Department of Medicine, IU School of MedicineAn 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.