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

Details

Serval ID
serval:BIB_93D7C25F949E
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
Modulation of GABAA receptors in cerebellar granule neurons by ethanol: a review of genetic and electrophysiological studies.
Journal
Alcohol
Author(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
Publication state
Published
Issued date
05/2007
Peer-reviewed
Oui
Volume
41
Number
3
Pages
187-199
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Review
Publication Status: ppublish
Abstract
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.

Keywords
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
Create date
31/01/2017 16:50
Last modification date
20/08/2019 15:56
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