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A mitochondrial‐targeted antioxidant improves myofilament Ca 2+ sensitivity during prolonged low frequency force depression at low P O 2
Author(s) -
Gandra Paulo G.,
Shiah Amy A.,
Nogueira Leonardo,
Hogan Michael C.
Publication year - 2018
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/jp275470
Subject(s) - myofibril , skeletal muscle , intracellular , reactive oxygen species , extracellular , mitochondrion , myofilament , antioxidant , mitochondrial ros , stimulation , sarcomere , muscle fatigue , medicine , chemistry , oxidative stress , endocrinology , myocyte , biology , biochemistry , neuroscience , electromyography
Key points Skeletal muscle contractile activity is associated with an enhanced reactive oxygen species (ROS) generation. At very low P O 2 , ROS generation by mitochondria can be elevated in intact cells. An elevated intracellular oxidant activity may affect muscle force development and recovery from fatigue. We treated intact single muscle fibres with a mitochondrial antioxidant and stimulated the fibres to contract at a low extracellular P O 2that is similar to the intracellular P O 2that is observed during moderate to intense exercise in vivo . The mitochondrial antioxidant prevented a sustained decrease in the myofibrillar Ca 2+ sensitivity and improved muscle submaximal force development after fatigue at low extracellular P O 2 .Abstract Skeletal muscle can develop a prolonged low frequency‐stimulation force depression (PLFFD) following fatigue‐inducing contractions. Increased levels of reactive oxygen species (ROS) have been implicated in the development of PLFFD. During exercise the skeletal muscle intracellular P O 2decreases to relatively low levels, and can be further decreased when there is an impairment in O 2 diffusion or availability, such as in certain chronic diseases and during exercise at high altitude. Since ROS generation by mitochondria is elevated at very low P O 2in cells, we tested the hypothesis that treatment of muscle fibres with a mitochondrial‐targeted antioxidant at a very low, near hypoxic, P O 2can attenuate PLFFD. We treated intact single fibres from mice with the mitochondrial‐specific antioxidant SS31, and measured force development and intracellular [Ca 2+ ] 30 min after fatigue at an extracellular P O 2of ∼5 Torr. After 30 min following the end of the fatiguing contractions, fibres treated with SS31 showed significantly less impairment in force development compared to untreated fibres at submaximal frequencies of stimulation. The cytosolic peak [Ca 2+ ] transients (peak [Ca 2+ ] c ) were equally decreased in both groups compared to pre‐fatigue values. The combined force and peak [Ca 2+ ] c data demonstrated that myofibrillar Ca 2+ sensitivity was diminished in the untreated fibres 30 min after fatigue compared to pre‐fatigue values, but Ca 2+ sensitivity was unaltered in the SS31 treated fibres. These results demonstrate that at a very low P O 2 , treatment of skeletal muscle fibres with a mitochondrial antioxidant prevents a decrease in the myofibrillar Ca 2+ sensitivity, which alleviates the fatigue induced PLFFD.