3 years ago

A mitochondrial-targeted antioxidant improves myofilament Ca2+ sensitivity during prolonged low frequency force depression at low PO2.

Michael C Hogan, Leonardo Nogueira, Amy A Shiah, Paulo G Gandra
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 PO2 decreases to relatively low levels, and can be further decreased when there is an impairment in O2 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 PO2 in cells, we tested the hypothesis that treatment of muscle fibres with a mitochondrial-targeted antioxidant at a very low, near hypoxic PO2 , can attenuate PLFFD. We treated intact single fibres from mice with the mitochondrial-specific antioxidant SS31, and measured force development and intracellular [Ca2+ ] 30 min after fatigue at an extracellular PO2 of ∼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 intracellular peak [Ca2+ ] transients (peak [Ca2+ ]c ) were equally decreased in both groups compared to pre-fatigue values. The combined force and peak [Ca2+ ]c data demonstrated that myofibrillar Ca2+ sensitivity was diminished in the untreated fibres 30 min after fatigue compared to pre-fatigue values, but Ca2+ sensitivity was unaltered in the SS31 treated fibres. These results demonstrate that at a very low PO2 , treatment of skeletal muscle fibres with a mitochondrial antioxidant prevents a decrease in the myofibrillar Ca2+ sensitivity, which alleviates the fatigue induced PLFFD. This article is protected by copyright. All rights reserved.

Publisher URL: http://doi.org/10.1113/JP275470

DOI: 10.1113/JP275470

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