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Antioxidant treatments do not improve force recovery after fatiguing stimulation of mouse skeletal muscle fibres
Author(s) -
Cheng Arthur J.,
Bruton Joseph D.,
Lanner Johanna T.,
Westerblad Håkan
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.279398
Subject(s) - muscle fatigue , skeletal muscle , antioxidant , chemistry , myofibril , nitric oxide , stimulation , reactive oxygen species , nitric oxide synthase , mitochondrion , endoplasmic reticulum , medicine , pharmacology , biochemistry , endocrinology , electromyography , physical medicine and rehabilitation
Key points Increased free radical production may contribute to decreased muscle force production during fatiguing exercise, and might delay recovery from fatigue. We exposed mouse fast‐twitch single fibres to antioxidants targeting specific cellular sites to determine whether these compounds delay fatigue development and/or improve the recovery from fatigue. Antioxidants had no effect on the fatigue‐induced decrease in contractile force. During recovery from fatigue, a mitochondria‐targeted antioxidant, SS‐31, restored the fatigue‐induced decrease in sarcoplasmic reticulum Ca 2+ release, but did not improve force recovery. We conclude that antioxidants cannot counteract the force decline during or after induction of muscle fatigue, although they may affect the underlying mechanisms.Abstract 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 [Ca 2+ ] ([Ca 2+ ] i ) and/or decreased myofibrillar Ca 2+ 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 150 ms, 70 Hz tetani given every 1 s. 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 [Ca 2+ ] i and peak force were reduced by ∼20% and ∼70% at the end of fatiguing stimulation, respectively, with no marked differences between groups. PLFFD was similar in all groups, with 30 Hz force being decreased by ∼60% at 30 min of recovery. PLFFD was mostly due to decreased tetanic [Ca 2+ ] 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 [Ca 2+ ] i was not decreased during recovery so PLFFD was only caused by decreased myofibrillar Ca 2+ sensitivity. The cocktail also increased resting [Ca 2+ ] i and ultimately caused cell death. In conclusion, ROS/RNS‐neutralizing compounds did not counteract the force decline during or after induction of fatigue.