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- Title
Nitric oxide down-regulates voltage-gated Na+ channel in cardiomyocytes possibly through S-nitrosylation-mediated signaling.
- Authors
Wang, Pu; Wei, Mengyan; Zhu, Xiufang; Liu, Yangong; Yoshimura, Kenshi; Zheng, Mingqi; Liu, Gang; Kume, Shinichiro; Morishima, Masaki; Kurokawa, Tatsuki; Ono, Katsushige
- Abstract
Nitric oxide (NO) is produced from endothelial cells and cardiomyocytes composing the myocardium and benefits cardiac function through both vascular-dependent and—independent effects. This study was purposed to investigate the possible adverse effect of NO focusing on the voltage-gated Na+ channel in cardiomyocytes. We carried out patch-clamp experiments on rat neonatal cardiomyocytes demonstrating that NOC-18, an NO donor, significantly reduced Na+ channel current in a dose-dependent manner by a long-term application for 24 h, accompanied by a reduction of Nav1.5-mRNA and the protein, and an increase of a transcription factor forkhead box protein O1 (FOXO1) in the nucleus. The effect of NOC-18 on the Na+ channel was blocked by an inhibitor of thiol oxidation N-ethylmaleimide, a disulfide reducing agent disulfide 1,4-Dithioerythritol, or a FOXO1 activator paclitaxel, suggesting that NO is a negative regulator of the voltage-gated Na+ channel through thiols in regulatory protein(s) for the channel transcription.
- Subjects
NITRIC oxide; SODIUM channels; HEART cells; NITROSYLATION; CELLULAR signal transduction
- Publication
Scientific Reports, 2021, Vol 11, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-021-90840-0