Redox modulation of maximum force production of fast- and slow-twitch skeletal muscles of rats and mice

Abstract

We used intact fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles from rats and mice to test the hypothesis that exogenous application of an oxidant would increase maximum isometric force production (Po) of slow-twitch muscles to a greater extent than fast-twitch skeletal muscles. Exposure to an oxidant, hydrogen peroxide (H2O2; 100 μM to 5 mM, 30 min), affected Po of rat muscles in a time- and dose-dependent manner. Po of rat soleus muscles was increased by 8 ± 1 (SE) and 14 ± 1% (P < 0.01) after incubation with 1 and 5 mM H2O2, respectively, whereas in mouse soleus muscles Po was only increased after incubation with 500 μM H2O2. Po of rat EDL muscles was affected by H2O2 biphasically; initially there was a small increase (3 ± 1%), but then Po diminished significantly after 30 min of treatment. In contrast, all concentrations of H2O2 tested decreased po of mouse EDL muscles. A reductant, dithiothreitol (DTT; rat = 10 mM, mouse = 1 mM), was added to quench H2O2, and it reversed the potentiation in Po in rat soleus but not in rat EDL muscles or in any H2O2-treated mouse muscles. After prolonged equilibration (30 min) with 5 mM H2O2 without prior activation, Po was potentiated in rat soleus but not EDL muscles, demonstrating that the effect of oxidation in the soleus muscles was also dependent on the activation history of the muscle. The results of these experiments demonstrate that Po of both slow- and fast-twitch muscles from rats and mice is modified by redox modulation, indicating that maximum Po of mammalian skeletal muscles is dependent on oxidation.