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Effect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse
Author(s) -
Andrade Francisco H.,
Reid Michael B.,
Allen David G.,
Westerblad Håkan
Publication year - 1998
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 - 10.1111/j.1469-7793.1998.565bn.x
Subject(s) - dithiothreitol , myofibril , chemistry , skeletal muscle , hydrogen peroxide , endoplasmic reticulum , medicine , calcium , biophysics , endocrinology , serca , biochemistry , biology , atpase , enzyme , organic chemistry
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 (H 2 O 2 , 100‐300 μM) for brief periods did not change myoplasmic Ca 2+ concentrations ([Ca 2+ ] i ) during submaximal tetani. However, force increased by 27 % during the same contractions. 3 The effects of H 2 O 2 were time dependent. Prolonged exposures resulted in increased resting and tetanic [Ca 2+ ] i , while force was significantly diminished. The force decline was mainly due to reduced myofibrillar Ca 2+ sensitivity. There was also evidence of altered sarcoplasmic reticulum (SR) function: passive Ca 2+ leak was increased and Ca 2+ uptake was decreased. 4 The reductant dithiothreitol (DTT, 0.5‐1 mM) did not change tetanic [Ca 2+ ] i , but decreased force by over 40 %. This was completely reversed by subsequent incubations with H 2 O 2 . The force decline induced by prolonged exposure to H 2 O 2 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 Ca 2+ sensitivity appears to be especially susceptible, while the SR functions (Ca 2+ leak and uptake) are less so.