Abstract
This study investigated the effect of S-glutathionylation on passive force in skeletal muscle fibres, to determine whether activity-related redox reactions could modulate the passive force properties of muscle. Mechanically-skinned fibres were freshly obtained from human and rat muscle, setting sarcomere length (SL) by laser diffraction. Larger stretches were required to produce passive force in human fibres compared to rat fibres, but there were no fibre-type differences in either species. When fibres were exposed to glutathione disulfide (GSSG; 20 mM, 15 min) whilst stretched (at a SL where passive force reached ~ 20% of maximal Ca2+-activated force, denoted as SL20 % max), passive force was subsequently decreased at all SLs in both type I and type II fibres of rat and human (e.g., passive force at SL20 % max decreased by 12 to 25%). This decrease was fully reversed by subsequent reducing treatment with dithiothreitol (DTT; 10 mM for 10 min). If freshly skinned fibres were initially treated with DTT, there was an increase in passive force in type II fibres (by 10 ± 3% and 9 ± 2% in rat and human fibres, respectively), but not in type I fibres. These results indicate that (i) S-glutathionylation, presumably in titin, causes a decrease in passive force in skeletal muscle fibres, but the reduction is relatively smaller than that reported in cardiac muscle, (ii) in rested muscle in vivo, there appears to be some level of reversible oxidative modification, probably involving S-glutathionylation of titin, in type II fibres, but not in type I fibres.
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Acknowledgements
We thank Heidy Flores for technical assistance. The monoclonal antibodies used in the present study were obtained from the Development Studies Hybridoma Bank, under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242, USA. The monoclonal antibodies directed against adult human MHC isoforms (A4.840 and A4.74) used in the present study were developed by Dr. H. Blau and that for MHC IIx (6H1) was developed by Dr. C. Lucas. We thank the National Health and Medical Research Council of Australia for financial support (Grant No. 1085331).
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Watanabe, D., Lamboley, C.R. & Lamb, G.D. Effects of S-glutathionylation on the passive force–length relationship in skeletal muscle fibres of rats and humans. J Muscle Res Cell Motil 41, 239–250 (2020). https://doi.org/10.1007/s10974-019-09563-5
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DOI: https://doi.org/10.1007/s10974-019-09563-5