Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice

Joseph D. Bruton, Nicolas Place, Takashi Yamada, José P. Silva, Francisco H. Andrade, Anders J. Dahlstedt, Shi Jin Zhang, Abram Katz, Nils Göran Larsson, Håkan Westerblad

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Skeletal muscle often shows a delayed force recovery after fatiguing stimulation, especially at low stimulation frequencies. In this study we focus on the role of reactive oxygen species (ROS) in this fatigue-induced prolonged low-frequency force depression. Intact, single muscle fibres were dissected from flexor digitorum brevis (FDB) muscles of rats and wild-type and superoxide dismutase 2 (SOD2) overexpressing mice. Force and myoplasmic free [Ca2+] ([Ca2+]i) were measured. Fibres were stimulated at different frequencies before and 30 min after fatigue induced by repeated tetani. The results show a marked force decrease at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This decrease was associated with reduced tetanic [Ca2+]i in wild-type mouse fibres, whereas rat fibres and mouse SOD2 overexpressing fibres instead displayed a decreased myofibrillar Ca2+ sensitivity. The SOD activity was ∼50% lower in wild-type mouse than in rat FDB muscles. Myoplasmic ROS increased during repeated tetanic stimulation in rat fibres but not in wild-type mouse fibres. The decreased Ca2+ sensitivity in rat fibres could be partially reversed by application of the reducing agent dithiothreitol, whereas the decrease in tetanic [Ca2+]i in wild-type mouse fibres was not affected by dithiothreitol or the antioxidant N-acetylcysteine. In conclusion, we describe two different causes of fatigue-induced prolonged low-frequency force depression, which correlate to differences in SOD activity and ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca2+ handling appear more resistant to interventions.

Original languageEnglish (US)
Pages (from-to)175-184
Number of pages10
JournalJournal of Physiology
Volume586
Issue number1
DOIs
StatePublished - Jan 1 2008

ASJC Scopus subject areas

  • Physiology

Fingerprint Dive into the research topics of 'Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice'. Together they form a unique fingerprint.

  • Cite this

    Bruton, J. D., Place, N., Yamada, T., Silva, J. P., Andrade, F. H., Dahlstedt, A. J., Zhang, S. J., Katz, A., Larsson, N. G., & Westerblad, H. (2008). Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice. Journal of Physiology, 586(1), 175-184. https://doi.org/10.1113/jphysiol.2007.147470