Effects of S-glutathionylation on the passive force–length relationship in skeletal muscle fibres of rats and humans
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Lamboley, Cedric R.
Lamb, Graham D.
This study investigated the efect of S-glutathionylation on passive force in skeletal muscle fbres, to determine whether activity-related redox reactions could modulate the passive force properties of muscle. Mechanically-skinned fbres were freshly obtained from human and rat muscle, setting sarcomere length (SL) by laser difraction. Larger stretches were required to produce passive force in human fbres compared to rat fbres, but there were no fbre-type diferences in either species. When fbres were exposed to glutathione disulfde (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 fbres 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 fbres were initially treated with DTT, there was an increase in passive force in type II fbres (by 10±3% and 9±2% in rat and human fbres, respectively), but not in type I fbres. These results indicate that (i) S-glutathionylation, presumably in titin, causes a decrease in passive force in skeletal muscle fbres, 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 modifcation, probably involving S-glutathionylation of titin, in type II fbres, but not in type I fbres.
We thank the National Health and Medical Research Council of Australia for financial support (Grant No. 1085331).
Journal of Muscle Research and Cell Motility
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Graduate School of Humanities and Social Sciences