Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse

Francisco H. Andrade, Michael B. Reid, David G. Allen, Håkan Westerblad

Research output: Contribution to journalArticlepeer-review

361 Scopus citations

Abstract

1. We used intact single fibres from a mouse foot muscle to study the role of oxidation-reduction in the modulation of contractile function. 2. The oxidant hydrogen peroxide (H2O2, 100-300 μM) for brief periods did not change myoplasmic Ca2+ concentrations ([Ca2+](i)) during submaximal tetani. However, force increased by 27% during the same contractions. 3. The effects of H2O2 were time dependent. Prolonged exposures resulted in increased resting and tetanic [Ca2+](i), while force significantly diminished. The force decline was mainly due to reduced myofibrillar Ca2+ sensitivity. There was also evidence of altered sarcoplasmic reticulum (SR) function: passive Ca2+ leak was increased and Ca2+ uptake was decreased. 4. The reductant dithiothreitol (DTT, 0.5-1 mM) did not change tetanic [Ca2+](i), but decreased force by over 40%. This was completely reversed by subsequent incubations with H2O2. The force decline induced by prolonged exposure to H2O2 was reversed by subsequent exposure to DTT. 5. These results show that the elements of the contractile machinery are differentially responsive to changes in the oxidation-reduction balance of the muscle fibres. Myofibrillar Ca2+ sensitivity appears to be especially susceptible, while the SR functions (Ca2+ leak and uptake) are less so.

Original languageEnglish
Pages (from-to)565-575
Number of pages11
JournalJournal of Physiology
Volume509
Issue number2
DOIs
StatePublished - Jun 1 1998

ASJC Scopus subject areas

  • Physiology

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