Inhibition of voltage-gated Na(+) currents in sensory neurones by the sea anemone toxin APETx2.

Détails

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Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_D93E54D323AD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Inhibition of voltage-gated Na(+) currents in sensory neurones by the sea anemone toxin APETx2.
Périodique
British Journal of Pharmacology
Auteur(s)
Blanchard M.G., Rash L.D., Kellenberger S.
ISSN
1476-5381 (Electronic)
ISSN-L
0007-1188
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
165
Numéro
7
Pages
2167-2177
Langue
anglais
Notes
Publication types: Journal Article
Résumé
BACKGROUND AND PURPOSE: APETx2, a toxin from the sea anemone Anthropleura elegantissima, inhibits acid-sensing ion channel 3 (ASIC3)-containing homo- and heterotrimeric channels with IC(50) values < 100 nM and 0.1-2 µM respectively. ASIC3 channels mediate acute acid-induced and inflammatory pain response and APETx2 has been used as a selective pharmacological tool in animal studies. Toxins from sea anemones also modulate voltage-gated Na(+) channel (Na(v) ) function. Here we tested the effects of APETx2 on Na(v) function in sensory neurones.¦EXPERIMENTAL APPROACH: Effects of APETx2 on Na(v) function were studied in rat dorsal root ganglion (DRG) neurones by whole-cell patch clamp.¦KEY RESULTS: APETx2 inhibited the tetrodotoxin (TTX)-resistant Na(v) 1.8 currents of DRG neurones (IC(50) , 2.6 µM). TTX-sensitive currents were less inhibited. The inhibition of Na(v) 1.8 currents was due to a rightward shift in the voltage dependence of activation and a reduction of the maximal macroscopic conductance. The inhibition of Na(v) 1.8 currents by APETx2 was confirmed with cloned channels expressed in Xenopus oocytes. In current-clamp experiments in DRG neurones, the number of action potentials induced by injection of a current ramp was reduced by APETx2.¦CONCLUSIONS AND IMPLICATIONS: APETx2 inhibited Na(v) 1.8 channels, in addition to ASIC3 channels, at concentrations used in in vivo studies. The limited specificity of this toxin should be taken into account when using APETx2 as a pharmacological tool. Its dual action will be an advantage for the use of APETx2 or its derivatives as analgesic drugs.
Pubmed
Web of science
Création de la notice
28/04/2012 8:34
Dernière modification de la notice
20/10/2020 10:08
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