Modulation of GABAA receptors in cerebellar granule neurons by ethanol: a review of genetic and electrophysiological studies.

Détails

ID Serval
serval:BIB_93D7C25F949E
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Modulation of GABAA receptors in cerebellar granule neurons by ethanol: a review of genetic and electrophysiological studies.
Périodique
Alcohol
Auteur(s)
Botta P., Radcliffe R.A., Carta M., Mameli M., Daly E., Floyd K.L., Deitrich R.A., Valenzuela C.F.
ISSN
0741-8329 (Print)
ISSN-L
0741-8329
Statut éditorial
Publié
Date de publication
05/2007
Peer-reviewed
Oui
Volume
41
Numéro
3
Pages
187-199
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Review
Publication Status: ppublish
Résumé
Cerebellar granule neurons (CGNs) receive inhibitory input from Golgi cells in the form of phasic and tonic currents that are mediated by postsynaptic and extrasynaptic gamma-aminobutyric acid type A (GABAA) receptors, respectively. Extrasynaptic receptors are thought to contain alpha6betaxdelta subunits. Here, we review studies on ethanol (EtOH) modulation of these receptors, which have yielded contradictory results. Although studies with recombinant receptors expressed in Xenopus oocytes indicate that alpha6beta3delta receptors are potently enhanced by acute exposure to low (>or=3 mM) EtOH concentrations, this effect was not observed when these receptors were expressed in Chinese hamster ovary cells. Slice recordings of CGNs have consistently shown that EtOH increases the frequency of phasic spontaneous inhibitory postsynaptic currents (sIPSCs), as well as the tonic current amplitude and noise. However, there is a lack of consensus as to whether EtOH directly acts on extrasynaptic receptors or modulates them indirectly; that is, via an increase in spillover of synaptically released GABA. It was recently demonstrated that an R to Q mutation of amino acid 100 of the alpha6 subunit increases the effect of EtOH on both sIPSCs and tonic current. These electrophysiological findings have not been reproducible in our hands. Moreover, it was shown the alpha6-R100Q mutation enhances sensitivity to the motor-impairing effects of EtOH in outbred Sprague-Dawley rats, but this was not observed in a line of rats selectively bred for high sensitivity to EtOH-induced motor alterations (Alcohol Non-Tolerant rats). We conclude that currently there is insufficient evidence conclusively supporting a direct potentiation of extrasynaptic GABAA receptors following acute EtOH exposure in CGNs.

Mots-clé
Animals, Central Nervous System Depressants/pharmacology, Cerebellum/cytology, Cerebellum/drug effects, Cerebellum/metabolism, Electrophysiology, Ethanol/pharmacology, Humans, Neurons/drug effects, Neurons/metabolism, Rats, Rats, Sprague-Dawley, Receptors, GABA-A/drug effects, Receptors, GABA-A/genetics, Receptors, GABA-A/physiology, Synaptic Transmission/drug effects
Pubmed
Création de la notice
31/01/2017 16:50
Dernière modification de la notice
03/03/2018 19:36
Données d'usage