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Elevation of NO Increases Ca2+ Entry and Resting Ca2+ and Na+ Concentrations in Skeletal Muscle Cells
Autor | dc.contributor.author | Robin, Gaelle | |
Autor | dc.contributor.author | Altamirano, Francisco | |
Autor | dc.contributor.author | Zhang, Rui | |
Autor | dc.contributor.author | Jaimovich Pérez, Enrique | |
Autor | dc.contributor.author | Allen, Paul D. | |
Autor | dc.contributor.author | López, José R. | |
Fecha ingreso | dc.date.accessioned | 2015-12-15T02:27:22Z | |
Fecha disponible | dc.date.available | 2015-12-15T02:27:22Z | |
Fecha de publicación | dc.date.issued | 2015 | |
Cita de ítem | dc.identifier.citation | Biophysical Journal | Vol 108, Iss 2 jan 2015 | en_US |
Identificador | dc.identifier.issn | 0006-3495 | |
Identificador | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/135719 | |
Nota general | dc.description | Artículo de publicación ISI | en_US |
Nota general | dc.description | Sin acceso a texto completo | |
Resumen | dc.description.abstract | Protein S-nitrosylation is a reversible post-translational modification and can have profound effects on protein function in skeletal muscle. S-nitrosylation has been proposed to exert regulatory effects on ion channels such as RyR1 and TRPCs, by modifying the redox state of critical thiols. Increased nitric oxide (NO) levels may play a crucial role in the alteration of intracellular resting [Ca 2þ ]r and [Naþ]r homeostasis in skeletal muscle. The present work aimed to characterize the contribution of NO using the nitric oxide donor S-nitroso-Nacetylpenicillamine (SNAP) on intracellular Ca 2þ and Naþ homeostasis in Wt myotubes. In quiescent Wt myotubes 100 mM SNAP increased Ca 2þ entry, [Ca 2þ ]r and [Naþ]r. These effects could be blocked with either Gd3þ or BTP-2 and partially reversed by DTT, a known inhibitor of S nitrosylation, suggesting that the effect of SNAP was through a reversible increase in the TRPC channel activity. Furthermore, we found that RyRs are not the principal target for S-nitrosylation because SNAP incubation increases [Ca 2þ ]r and [Naþ]r in RyR1/RYR3 null myotubes. It is known that NO production is elevated in mdx muscle. Here we found that DTT or BTP-2 significantly reduced [Ca 2þ ]r in mdx myotubes and DTT was able to restore a normal Ca 2þ entry. We then looked at the effects of SNAP on K þ induced Ca 2þ release and SR Ca 2þ content in WT and mdx myotubes. SNAP did not significantly decrease sarcoplasmic reticulum Ca 2þ content in either WT or mdx myotubes but reduced the magnitude of the Ca 2þ transient induced by K þ in Wt but not in mdx myotubes. These results suggest that nitrosative modifications play a key role regulating TRPC activity in muscular dystrophy and their role in the Ca 2þ and Naþ overload seen in dystrophic muscles. | en_US |
Idioma | dc.language.iso | en | en_US |
Publicador | dc.publisher | Cell Press | en_US |
Tipo de licencia | dc.rights | Atribución-NoComercial-SinDerivadas 3.0 Chile | * |
Link a Licencia | dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | * |
Título | dc.title | Elevation of NO Increases Ca2+ Entry and Resting Ca2+ and Na+ Concentrations in Skeletal Muscle Cells | en_US |
Tipo de documento | dc.type | Artículo de revista |
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