PMID- 23911204
OWN - NLM
STAT- MEDLINE
DCOM- 20140415
LR  - 20191210
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 64
IP  - 1
DP  - 2013 Oct
TI  - Tumor Necrosis Factor alpha induced hypoexcitability in rat muscle evidenced in a 
      model of ion currents and action potential.
PG  - 165-71
LID - S1043-4666(13)00601-7 [pii]
LID - 10.1016/j.cyto.2013.07.007 [doi]
AB  - Sepsis and Tumor Necrosis Factor alpha (TNFalpha), a major pro-inflammatory mediator, 
      have previously been shown to induce a decrease in the conductance of 
      voltage-dependent sodium channels (NaV). Moreover, TNFalpha increased resting 
      membrane potential, leading to hyperpolarization. NaV and resting potential are 
      the two major factors of membrane excitability. Then we hypothesis that TNFalpha can 
      decrease muscle membrane excitability. To evidence that role of TNFalpha, 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 TNFalpha-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 TNFalpha-containing medium, thus 
      corresponding to a decreased excitability.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Guillouet, Maite
AU  - Guillouet M
AD  - Universite de Brest, Faculte de Medecine et des Sciences de la Sante, Laboratoire 
      de Physiologie, EA 1274 "Mouvement Sport Sante", Brest F-29200, France; 
      Universite Europeenne de Bretagne, Brest F-29200, France; CHU Brest, Pole 
      Anesthesie Reanimation, Brest F-29200, France.
FAU - Rannou, Fabrice
AU  - Rannou F
FAU - Giroux-Metges, Marie-Agnes
AU  - Giroux-Metges MA
FAU - Droguet, Mickael
AU  - Droguet M
FAU - Pennec, Jean-Pierre
AU  - Pennec JP
LA  - eng
PT  - Journal Article
DEP - 20130802
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Voltage-Gated Sodium Channels)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
SB  - IM
MH  - Action Potentials/*physiology
MH  - Animals
MH  - Computer Simulation
MH  - Female
MH  - Inflammation/metabolism
MH  - Membrane Potentials/*physiology
MH  - Muscle Fibers, Skeletal/*metabolism/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Sepsis/metabolism
MH  - Sodium-Potassium-Exchanging ATPase/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Voltage-Gated Sodium Channels/metabolism/physiology
OTO - NOTNLM
OT  - Action potential
OT  - Excitability
OT  - Ion currents
OT  - Muscle
OT  - TNFalpha
EDAT- 2013/08/06 06:00
MHDA- 2014/04/16 06:00
CRDT- 2013/08/06 06:00
PHST- 2013/01/28 00:00 [received]
PHST- 2013/06/14 00:00 [revised]
PHST- 2013/07/02 00:00 [accepted]
PHST- 2013/08/06 06:00 [entrez]
PHST- 2013/08/06 06:00 [pubmed]
PHST- 2014/04/16 06:00 [medline]
AID - S1043-4666(13)00601-7 [pii]
AID - 10.1016/j.cyto.2013.07.007 [doi]
PST - ppublish
SO  - Cytokine. 2013 Oct;64(1):165-71. doi: 10.1016/j.cyto.2013.07.007. Epub 2013 Aug 
      2.