Modulation of contractile apparatus Ca2+ sensitivity and disruption of excitation–contraction coupling by S‐nitrosoglutathione in rat muscle fibres
- 27 April 2011
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 589 (9), 2181-2196
- https://doi.org/10.1113/jphysiol.2010.200451
Abstract
S-Nitrosoglutathione (GSNO) is generated in muscle and may S-glutathionylate and/or S-nitrosylate various proteins involved in excitation–contraction (EC) coupling, such as Na+-K+-ATPases, voltage-sensors (VSs) and Ca2+ release channels (ryanodine receptors,RyRs), possibly changing their properties. Using mechanically skinned fibres from rat extensor digitorum longus muscle, we sought to identify which EC coupling processes are most susceptible to GSNO-modulated changes and whether these changes could be important in muscle function and fatigue. For comparison, we examined the effect of other oxidation, nitrosylation, or glutathionylation treatments (S-nitroso-N-acetyl-penicillamine (SNAP), hydrogen peroxide,2,2-dithiodipyridine and reduced glutathione) on twitch and tetanic force, action potential (AP) repriming, sarcoplasmic reticulum (SR) Ca2+ loading and leakage, and contractile apparatus properties. None of the treatments detectably altered AP repriming, indicating that t-system excitability was relatively insensitive to such oxidative modification. Importantly, the overall effect on twitch and tetanic force of a given treatment was determined primarily by its action on Ca2+ sensitivity of the contractile apparatus. For example, S-nitrosylation with the NO• donor,SNAP, caused matching decreases in the contractile Ca2+ sensitivity and twitch response, and GSNO applied ∼10 min after preparation had very similar effects. The only exception was when GSNO was applied immediately after preparation, which resulted in irreversible decreases in twitch and tetanic responses even though it concomitantly increased Ca2+ sensitivity by∼0.1 pCaunits, the latter evidently due to S-glutathionylation of the contractile apparatus. This decrease in AP-mediated force responses was due to impaired VS–RyR coupling and was accompanied by increased Ca2+ leakage through RyRs. Such oxidation-related impairment of coupling could be responsible for prolonged low frequency fatigue in certain circumstances.Keywords
This publication has 57 references indexed in Scilit:
- Acute effects of reactive oxygen and nitrogen species on the contractile function of skeletal muscleThe Journal of Physiology, 2011
- Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscleNature Medicine, 2009
- Calsequestrin content and SERCA determine normal and maximal Ca2+ storage levels in sarcoplasmic reticulum of fast‐ and slow‐twitch fibres of ratThe Journal of Physiology, 2009
- Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force ProductionPhysiological Reviews, 2008
- Hydroxyl radical and glutathione interactions alter calcium sensitivity and maximum force of the contractile apparatus in rat skeletal muscle fibresThe Journal of Physiology, 2008
- Chloride conductance in the transverse tubular system of rat skeletal muscle fibres: importance in excitation–contraction coupling and fatigueThe Journal of 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
- Ca2+sparks and T tubule reorganization in dedifferentiating adult mouse skeletal muscle fibersAmerican Journal of Physiology-Cell Physiology, 2007
- An investigation into the role of SH1 and SH2 groups of myosin in calcium binding and tension generationBiochemical and Biophysical Research Communications, 1980
- Cooperative role of two sulfhydryl groups in myosin adenosine triphosphataseBiochemistry, 1974