期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 593, 期 2, 页码 457-472出版社
WILEY
DOI: 10.1113/jphysiol.2014.279398
关键词
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资金
- Swedish Research Council
- Swedish National Center for Sports Research
- Association Francaise Contre les Myopathies (AFM)
- Lars Hierta Minne Stiftelsen
- Jeanssons Stiftelser
The contractile performance of skeletal muscle declines during intense activities, i.e. fatigue develops. Fatigued muscle can enter a state of prolonged low-frequency force depression (PLFFD). PLFFD can be due to decreased tetanic free cytosolic [Ca2+] ([Ca2+](i)) and/or decreased myofibrillar Ca2+ sensitivity. Increases in reactive oxygen and nitrogen species (ROS/RNS) may contribute to fatigue-induced force reductions. We studied whether pharmacological ROS/RNS inhibition delays fatigue and/or counteracts the development of PLFFD. Mechanically isolated mouse fast-twitch fibres were fatigued by sixty 150ms, 70Hz tetani given every 1s. Experiments were performed in standard Tyrode solution (control) or in the presence of: NADPH oxidase (NOX) 2 inhibitor (gp91ds-tat); NOX4 inhibitor (GKT137831); mitochondria-targeted antioxidant (SS-31); nitric oxide synthase (NOS) inhibitor (l-NAME); the general antioxidant N-acetylcysteine (NAC); a cocktail of SS-31, l-NAME and NAC. Spatially and temporally averaged [Ca2+](i) and peak force were reduced by approximate to 20% and approximate to 70% at the end of fatiguing stimulation, respectively, with no marked differences between groups. PLFFD was similar in all groups, with 30Hz force being decreased by approximate to 60% at 30min of recovery. PLFFD was mostly due to decreased tetanic [Ca2+](i) in control fibres and in the presence of NOX2 or NOX4 inhibitors. Conversely, in fibres exposed to SS-31 or the anti ROS/RNS cocktail, tetanic [Ca2+](i) was not decreased during recovery so PLFFD was only caused by decreased myofibrillar Ca2+ sensitivity. The cocktail also increased resting [Ca2+](i) and ultimately caused cell death. In conclusion, ROS/RNS-neutralizing compounds did not counteract the force decline during or after induction of fatigue.
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