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This Article Full Text Full Text (PDF) All Versions of this Article: 567/3/815    most recent jphysiol.2005.089599v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pouvreau, S. Articles by Jacquemond, V. Search for Related Content PubMed PubMed Citation Articles by Pouvreau, S. Articles by Jacquemond, V.

¹ Physiologie Intégrative Cellulaire et Moléculaire, Université Claude Bernard – Lyon 1, UMR CNRS 5123, Villeurbanne, France

Nitric oxide (NO) generated by skeletal muscle is believed to regulate force production but how this is achieved remains poorly understood. In the present work we tested the effects of NO synthase (NOs) inhibitors on membrane current and intracellular calcium in isolated skeletal muscle fibres from mouse, under voltage-clamp conditions. Resting [Ca²⁺] and [Ca²⁺] transients evoked by large depolarizations exhibited similar properties in control fibres and in fibres loaded with tenth millimolar levels of the NOs inhibitor N-nitro-L-arginine (L-NNA). Yet the voltage dependence of calcium release was found to be shifted by 15 mV towards negative values in the presence of L-NNA. This effect could be reproduced by the other NOs inhibitor S-methyl-L-thiocitrulline (L-SMT). Separate experiments showed that the voltage dependence of charge movement and of the slow calcium current were unaffected by the presence of L-NNA, ruling out an effect on the voltage sensor. A negative shift in the voltage dependence of calcium release with no concurrent alteration in the properties of charge movement was also observed in fibres exposed to the oxidant H₂O₂ (1 mM). Conversely the reducing agent dithiothreitol (10 mM) had no obvious effect on Ca²⁺ release. Overall, the results indicate that physiological levels of NO exert a tonic inhibitory control on the activation of the calcium release channels. Changes in the voltage dependence of Ca²⁺ release activation may be a ubiquitous physiological consequence of redox-related modifications of the ryanodine receptor.

(Received 29 April 2005; accepted after revision 30 June 2005; first published online 1 July 2005)
Corresponding author V. Jacquemond: Physiologie Intégrative Cellulaire et Moléculaire, Université Claude Bernard – Lyon 1, UMR CNRS 5123, Bât. Raphael Dubois, 43 boulevard du 11 novembre 1918, F 69622 Villeurbanne Cedex, France. Email: vincent.jacquemond{at}univ-lyon1.fr

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