Hydroxyl radical and glutathione interactions alter calcium sensitivity and maximum force of the contractile apparatus in rat skeletal muscle fibres
- 14 April 2008
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 586 (8), 2203-2216
- https://doi.org/10.1113/jphysiol.2007.150516
Abstract
Studies on intact muscle fibres indicate that reactive oxygen species (ROS) produced during muscle activity, or applied exogenously, can cause decreased force responses primarily by reducing the Ca(2+) sensitivity of the contractile apparatus. Identification of the molecular basis of this effect is complicated by the fact that studies on skinned muscle fibres in general have not observed reduced contractile Ca(2+) sensitivity when applying ROS, predominantly H(2)O(2). Here, using skinned fibres from rat extensor digitorum longus (EDL) and soleus muscle, it is shown that although H(2)O(2) (> or = 100 microm) has little effect by itself, when added in the presence of myoglobin it causes marked reduction in the Ca(2+) sensitivity of the contractile apparatus, probably due to production of hydroxyl radicals (OH(*)). Maximum force production is also reduced, but only with larger or more prolonged treatments. The effects are not prevented by tempol, a potent superoxide scavenger. Dithiotreitol (DTT) produces little reversal of the sensitivity change if applied afterwards, but it does substantially reverse all the changes if applied before the fibre undergoes an activation sequence. When glutathione (GSH, 5 mM) is present, exposure of EDL fibres to H(2)O(2) and myoglobin causes an increase in Ca(2+) sensitivity, with longer treatments causing a subsequent decrease, whereas in soleus fibres it causes only decreases in sensitivity and maximum force. The increased Ca(2+) sensitivity in EDL fibres is evidently due to the summed actions of (i) a potentiating effect of glutathionylation, which can be reversed by DTT and only occurs in fast-twitch fibres, and (ii) a less reversible reduction in sensitivity. Western blotting showed that reductions in Ca(2+) sensitivity were not due to loss of troponin-C. The present findings help provide a mechanistic basis for diverse findings on the effects of ROS in muscle fibres and implicate OH(*) radicals and glutathione as likely mediators of the effects.Keywords
This publication has 40 references indexed in Scilit:
- Chloride conductance in the transverse tubular system of rat skeletal muscle fibres: importance in excitation–contraction coupling and fatigueThe Journal of Physiology, 2008
- Functional, structural, and chemical changes in myosin associated with hydrogen peroxide treatment of skeletal muscle fibersAmerican Journal of Physiology-Cell Physiology, 2008
- Reactive oxygen species and fatigue‐induced prolonged low‐frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing miceThe Journal of Physiology, 2008
- O2•−production at 37°C plays a critical role in depressing tetanic force of isolated rat and mouse skeletal muscleAmerican Journal of Physiology-Cell Physiology, 2007
- Ca2+ activation of diffusible and bound pools of μ‐calpain in rat skeletal muscleThe Journal of Physiology, 2006
- Effects of Congestive Heart Failure on Ca 2+ Handling in Skeletal Muscle During FatigueCirculation Research, 2006
- Long-lasting muscle fatigue: partial disruption of excitation-contraction coupling by elevated cytosolic Ca2+ concentration during contractionsAmerican Journal of Physiology-Cell Physiology, 2006
- Calcium phosphate precipitation in the sarcoplasmic reticulum reduces action potential-mediated Ca2+release in mammalian skeletal muscleAmerican Journal of Physiology-Cell Physiology, 2005
- Effects of oxidation and cytosolic redox conditions on excitation–contraction coupling in rat skeletal muscleThe Journal of Physiology, 2003
- Reversible changes in Ca2+‐activation properties of rat skeletal muscle exposed to elevated physiological temperaturesThe Journal of Physiology, 2002