期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 76, 期 -, 页码 247-256出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2014.09.009
关键词
Late sodium current; ATX-II; RyRs; CaMKII; ROS; Mitochondria
资金
- National Institutes of Health (NIH) [R01-HL079031, R01-HL096652, R01-HL070250, R01-HL071140]
- Gilead Sciences Inc.
An increase of late Na+ current (I-NaL) 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 I-NaL 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. (C) 2014 The Authors. Published by Elsevier Ltd.
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