Tumor Necrosis Factor alpha induced hypoexcitability in rat muscle evidenced in a model of ion currents and action potential. - Université de Bretagne Occidentale Access content directly
Journal Articles Cytokine Year : 2013

Tumor Necrosis Factor alpha induced hypoexcitability in rat muscle evidenced in a model of ion currents and action potential.

Maïté Guillouët
  • Function : Author
Fabrice Rannou
Marie-Agnès Giroux-Metges
  • Function : Author
Mickael Droguet
  • Function : Author
Jean-Pierre Pennec
  • Function : Author

Abstract

Sepsis and Tumor Necrosis Factor alpha (TNFα), a major pro-inflammatory mediator, have previously been shown to induce a decrease in the conductance of voltage-dependent sodium channels (NaV). Moreover, TNFα increased resting membrane potential, leading to hyperpolarization. NaV and resting potential are the two major factors of membrane excitability. Then we hypothesis that TNFα can decrease muscle membrane excitability. To evidence that role of TNFα, we carried out a simulation of the sodium and potassium currents and action potential (AP) of isolated muscle fibre. We used a computer model based on Hodgkin and Huxley equations, but also taking into account the sodium-potassium pump current. Our first aim was to optimise this model in control conditions according to our measurements of currents. Then the model was modified to fit the values measured experimentally in TNFα-containing medium in order to determine the modifications induced in the currents and hence in AP triggering. Our model provides a very good fit with experimental data on the ion currents. Moreover, it clearly shows that the triggering level of AP is increased in TNFα-containing medium, thus corresponding to a decreased excitability.

Dates and versions

hal-00881585 , version 1 (08-11-2013)

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Maïté Guillouët, Fabrice Rannou, Marie-Agnès Giroux-Metges, Mickael Droguet, Jean-Pierre Pennec. Tumor Necrosis Factor alpha induced hypoexcitability in rat muscle evidenced in a model of ion currents and action potential.. Cytokine, 2013, 64 (1), pp.165-71. ⟨10.1016/j.cyto.2013.07.007⟩. ⟨hal-00881585⟩
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