title: Intracellular Na+ overload causes oxidation of CaMKII and leads to Ca2+ mishandling in isolated ventricular myocytes.
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.
authors.affiliation: Department of Biology, Gilead Sciences, Fremont, CA 94555, USA. Electronic address: Serge.Karpinski@gilead.com.
authors.forename: Serge
authors.initials: S
authors.lastname: Viatchenko-Karpinski
authors.affiliation: Department of Biology, Gilead Sciences, Fremont, CA 94555, USA.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Kornyeyev
authors.affiliation: Department of Biology, Gilead Sciences, Fremont, CA 94555, USA.
authors.forename: Nesrine
authors.initials: N
authors.lastname: El-Bizri
authors.affiliation: Department of Biology, Gilead Sciences, Fremont, CA 94555, USA.
authors.forename: Grant
authors.initials: G
authors.lastname: Budas
authors.affiliation: Department of Biology, Gilead Sciences, Fremont, CA 94555, USA.
authors.forename: Peidong
authors.initials: P
authors.lastname: Fan
authors.affiliation: Department of Biology, Gilead Sciences, Fremont, CA 94555, USA.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: University of Iowa Carver College of Medicine, Department of Internal Medicine, Iowa City, IA 52242, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Anderson
authors.affiliation: Department of Biology, Gilead Sciences, Fremont, CA 94555, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Shryock
authors.affiliation: Krannert Institute of Cardiology and Division of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Ching-Pin
authors.initials: CP
authors.lastname: Chang
authors.affiliation: Department of Biology, Gilead Sciences, Fremont, CA 94555, USA.
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.affiliation: Department of Biology, Gilead Sciences, Fremont, CA 94555, USA. Electronic address: Lina.Yao@gilead.com.
authors.forename: Lina
authors.initials: L
authors.lastname: Yao
mesh_terms: D000200:Action Potentials; D000818:Animals; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000201:enzymology; D042541:Intracellular Space / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000201:enzymology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D012964:Sodium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: ATX-II; CaMKII; Late sodium current; Mitochondria; ROS; RyRs