logo amu logo cnrs

UMR 7286 - Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille

Plates-formes PFRN

Accueil > Bibliographie > MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor (...)

MmTX1 and MmTX2 from coral snake venom potently (...)

Proc Natl Acad Sci U S A. 2015 Feb ;112(8):E891-900
MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activity.
Rosso JP, Schwarz JR, Diaz-Bustamante M, Ceard B, Gutierrez JM, Kneussel M, Pongs O, Bosmans F, Bougis PE.

GABAA receptors shape synaptic transmission by modulating Cl(-) conductance across the cell membrane. Remarkably, animal toxins that specifically target GABAA receptors have not been identified. Here, we report the discovery of micrurotoxin1 (MmTX1) and MmTX2, two toxins present in Costa Rican coral snake venom that tightly bind to GABAA receptors at subnanomolar concentrations. Studies with recombinant and synthetic toxin variants on hippocampal neurons and cells expressing common receptor compositions suggest that MmTX1 and MmTX2 allosterically increase GABAA receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the α(+)/β(-) interface. Moreover, hippocampal neuron excitability measurements reveal toxin-induced transitory network inhibition, followed by an increase in spontaneous activity. In concert, toxin injections into mouse brain result in reduced basal activity between intense seizures. Altogether, we characterized two animal toxins that enhance GABAA receptor sensitivity to agonist, thereby establishing a previously unidentified class of tools to study this receptor family.


Le CRN2M en chiffres

  • 20 Chercheurs
  • 18 Enseignants Chercheurs
  • 39 ITAs et IATOs
  • 3 Post-Docs
  • 5 Docs
  • 4 Étudiants de Master

    Ils nous font confiance

  • logo amu
  • logo cnrs
  • logo inserm
  • logo AP-HM
  • logo Galderma
  • logo Ipsem
  • logo Novartis
  • logo Pfizer
  • logo Fédération pour la Recherche sur le Cerveau
  • logo Fondation pour la Recherche Medical en France
  • logo IBiSA
  • logo Europe programme FEDER
  • logo Agence Nationale de la Recherche