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© Institut Pasteur
Visualisation des flux calciques dans une culture de neurones de la substance noire infectée avec un vecteur lentiviral pour l'expression spécifique d'un marqueur des flux calciques basé sur la eGFP (protéine bioluminescente sensible aux ions Calcium). Grâce à la détection de ces signaux bioluminescents, on peut visualiser des flux calciques simultanément dans un grand nombre de cellules permettant d'établir des corrélations spatiales entre les différents signaux calciques.
Publication : Nature communications

Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 01 Jan 2013

Sauguet L, Howard RJ, Malherbe L, Lee US, Corringer PJ, Harris RA, Delarue M

Link to Pubmed [PMID] – 23591864

Nat Commun 2013;4:1697

Ethanol alters nerve signalling by interacting with proteins in the central nervous system, particularly pentameric ligand-gated ion channels. A recent series of mutagenesis experiments on Gloeobacter violaceus ligand-gated ion channel, a prokaryotic member of this family, identified a single-site variant that is potentiated by pharmacologically relevant concentrations of ethanol. Here we determine crystal structures of the ethanol-sensitized variant in the absence and presence of ethanol and related modulators, which bind in a transmembrane cavity between channel subunits and may stabilize the open form of the channel. Structural and mutagenesis studies defined overlapping mechanisms of potentiation by alcohols and anaesthetics via the inter-subunit cavity. Furthermore, homology modelling show this cavity to be conserved in human ethanol-sensitive glycine and GABA(A) receptors, and to involve residues previously shown to influence alcohol and anaesthetic action on these proteins. These results suggest a common structural basis for ethanol potentiation of an important class of targets for neurological actions of ethanol.

http://www.ncbi.nlm.nih.gov/pubmed/23591864