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Tumor necrosis factor-α downregulates sodium current in skeletal muscle by protein kinase C activation: involvement in critical illness polyneuromyopathy.
Guillouet, Maité; Gueret, Gildas; Rannou, Fabrice; Giroux-Metges, Marie-Agnès; Gioux, Maxime; Arvieux, Charles C; Pennec, Jean-Pierre.
Afiliación
  • Guillouet M; Faculté de Médecine et des Sciences de la Santé, Laboratoire de Physiologie, Université de Brest, Brest, France.
Am J Physiol Cell Physiol ; 301(5): C1057-63, 2011 Nov.
Article en En | MEDLINE | ID: mdl-21795525
Sepsis is involved in the decrease of membrane excitability of skeletal muscle, leading to polyneuromyopathy. This effect is mediated by alterations of the properties of voltage-gated sodium channels (Na(V)), but the exact mechanism is still unknown. The aim of the present study was to check whether tumor necrosis factor (TNF-α), a cytokine released during sepsis, exerts a rapid effect on Na(V). Sodium current (I(Na)) was recorded by macropatch clamp in skeletal muscle fibers isolated from rat peroneus longus muscle, in control conditions and after TNF-α addition. Analyses of dose-effect and time-effect relationships were carried out. Effect of chelerythrine, a PKC inhibitor, was also studied to determine the way of action of TNF-α. TNF-α induced a reversible dose- and time-dependent inhibition of I(Na). A maximum inhibition of 75% of the control current was observed. A shift toward more negative potentials of activation and inactivation curves of I(Na) was also noticed. These effects were prevented by chelerythrine pretreatment. TNF-α is a cytokine released in the early stages of sepsis. Besides a possible transcriptional role, i.e., modification of the channel type and/or number, we demonstrated the existence of a rapid, posttranscriptional inhibition of Na(V) by TNF-α. The downregulation of the sodium current could be mediated by a PKC-induced phosphorylation of the sodium channel, thus leading to a significant decrease in muscle excitability.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polineuropatías / Proteína Quinasa C / Canales de Sodio / Factor de Necrosis Tumoral alfa / Fibras Musculares Esqueléticas Límite: Animals Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polineuropatías / Proteína Quinasa C / Canales de Sodio / Factor de Necrosis Tumoral alfa / Fibras Musculares Esqueléticas Límite: Animals Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Francia