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

J Mol Cell Cardiol. 2014 Nov:76:247-56. doi: 10.1016/j.yjmcc.2014.09.009. Epub 2014 Sep 22.

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.

Keywords: ATX-II; CaMKII; Late sodium current; Mitochondria; ROS; RyRs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Calcium Signaling
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Female
  • Heart Ventricles / cytology
  • Heart Ventricles / enzymology
  • Intracellular Space / metabolism
  • Myocytes, Cardiac / enzymology*
  • Oxidation-Reduction
  • Oxidative Stress
  • Rabbits
  • Reactive Oxygen Species / metabolism
  • Sodium / metabolism*

Substances

  • Reactive Oxygen Species
  • Sodium
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2