Modulation of GABAA receptors in cerebellar granule neurons by ethanol: a review of genetic and electrophysiological studies
Alcohol. 2007-05-01; 41(3): 187-199
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1. Alcohol. 2007 May;41(3):187-99. Epub 2007 May 23.
Modulation of GABAA receptors in cerebellar granule neurons by ethanol: a review
of genetic and electrophysiological studies.
Botta P(1), Radcliffe RA, Carta M, Mameli M, Daly E, Floyd KL, Deitrich RA,
(1)Department of Neurosciences, MSC08 4740, 1 University of New Mexico Health
Sciences Center, Albuquerque, NM 87131-0001, USA.
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
PMID: 17521847 [Indexed for MEDLINE]