An increase of late Na+ current (INaL) 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 INaL 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.
- Late sodium current
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine