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https://hdl.handle.net/2440/34756
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Type: | Journal article |
Title: | Effects of oxidation and cytosolic redox conditions on excitation-contraction coupling in rat skeletal muscle |
Author: | Posterino, Giuseppe Saverio Cellini, M. A. Lamb, Graham D. |
Citation: | Journal of Physiology, 2003; 547 (3):807-823 |
Publisher: | Blackwell |
Issue Date: | 2003 |
ISSN: | 0022-3751 |
School/Discipline: | School of Molecular and Biomedical Science |
Statement of Responsibility: | G. S. Posterino, M. A. Cellini and G. D. Lamb |
Abstract: | In this study the effects of oxidation and reduction on various steps in the excitation-contraction (E–C) coupling sequence was examined in mammalian skeletal muscle. In mechanically skinned fast-twitch fibres, electric field stimulation was used to generate action potentials in the sealed transverse-tubular (T-) system, thereby eliciting twitch responses, which are a sensitive measure of Ca2+ release. Treatment of fibres with the oxidant H2O2 (200 μm and 10 mm) for 2–5 min markedly potentiated caffeine-induced Ca2+ release and the force response to partial depolarisation of the T-system (by solution substitution). Importantly, such H2O2 treatment had no effect at all on any aspect of the twitch response (peak amplitude, rate of rise, decay rate constant and half-width), except in cases where it interfered with the T-system potential or voltage-sensor activation, resulting in a reduction or abolition of the twitch response. Exposure to strong thiol reductants, dithiothreitol (DTT, 10 mm) and reduced glutathione (GSH, 5 mm), did not affect the twitch response over 5 min, nor did varying the glutathione ratio (reduced to oxidised glutathione) from the level present endogenously in the cytosol of a rested fibre (30:1) to the comparatively oxidised level of 3:1. In fibres that had been oxidised by H2O2 (10 mm) (or by 2,2'-dithiodipyridine, 100 μm), exposure to GSH (5 mm) caused potentiation of twitch force (by 20 % for H2O2); this effect was due to the increase in the Ca2+ sensitivity of the contractile apparatus that occurs under such circumstances and was fully reversed by subsequent exposure to 10 mm DTT. We conclude that: (a) the redox potential across the sarcomplamsic reticulum has no noticeable direct effect on normal E–C coupling in mammalian skeletal muscle, (b) oxidising the Ca2+-release channels and greatly increasing their sensitivity to Ca2+-induced Ca2+ release does not alter the amount of Ca2+ released by an action potential and (c) oxidation potentiates twitches by a GSH-mediated increase in the Ca2+ sensitivity of the contractile apparatus. |
Description: | The definitive version is available at www.blackwell-synergy.com |
DOI: | 10.1111/j.1469-7793.2003.00807.x |
Appears in Collections: | Molecular and Biomedical Science publications |
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