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Graded response to GABA by native extrasynaptic GABA(A) receptors

Lindquist, Catarina LU and Birnir, Bryndis LU (2006) In Journal of Neurochemistry 97(5). p.1349-1356
Abstract
GABA is the main inhibitory neurotransmitter in the mammalian CNS. GABA in the brain is commonly associated with a fast, point-to-point form of signalling called synaptic transmission (phasic inhibition), but there is growing evidence that GABA participates in another, slower and more diffuse form of signalling often referred to as tonic inhibition. Unresolved questions regarding tonic neuronal inhibition concern activation and functional properties of extrasynaptic GABA(A) receptors (GABARex) present on neurones. Extrasynaptic receptors are exposed to submicromolar GABA concentrations and may modulate the overall excitability of neurones and neuronal networks. Here, we examined GABA-activated single-channel currents in dentate gyrus... (More)
GABA is the main inhibitory neurotransmitter in the mammalian CNS. GABA in the brain is commonly associated with a fast, point-to-point form of signalling called synaptic transmission (phasic inhibition), but there is growing evidence that GABA participates in another, slower and more diffuse form of signalling often referred to as tonic inhibition. Unresolved questions regarding tonic neuronal inhibition concern activation and functional properties of extrasynaptic GABA(A) receptors (GABARex) present on neurones. Extrasynaptic receptors are exposed to submicromolar GABA concentrations and may modulate the overall excitability of neurones and neuronal networks. Here, we examined GABA-activated single-channel currents in dentate gyrus granule neurones in rat hippocampal slices. We activated three types (I, II, III) of GABARex channels by nanomolar GABA concentrations (EC50 I: 27 +/- 12; II: 4 +/- 3; III: 43 +/- 19 nM). The channels opened after a delay and the single-channel conductance was graded (gamma(max) I: 61 +/- 3; II: 85 +/- 8, III: 40 +/- 3 pS). The channels were differentially modulated by 1 mu M diazepam, 200 nM zolpidem, 1 mu M flumazenil and 50 nM THDOC (3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one), consistent with the following minimal subunit composition of GABARex I alpha(1)beta gamma(2), GABARex II alpha(4)beta gamma(2) and GABARex III alpha beta delta channels. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
single-channel current, patch-clamp, GABA channels, hippocampus, tonic, inhibition
in
Journal of Neurochemistry
volume
97
issue
5
pages
1349 - 1356
publisher
Wiley-Blackwell
external identifiers
  • wos:000237516700012
  • pmid:16573642
  • scopus:33646556407
ISSN
1471-4159
DOI
10.1111/j.1471-4159.2006.03811.x
language
English
LU publication?
yes
id
85a60365-6054-4bdf-99c9-138aa6e29607 (old id 156126)
date added to LUP
2007-07-25 15:36:32
date last changed
2019-02-20 07:51:57
@article{85a60365-6054-4bdf-99c9-138aa6e29607,
  abstract     = {GABA is the main inhibitory neurotransmitter in the mammalian CNS. GABA in the brain is commonly associated with a fast, point-to-point form of signalling called synaptic transmission (phasic inhibition), but there is growing evidence that GABA participates in another, slower and more diffuse form of signalling often referred to as tonic inhibition. Unresolved questions regarding tonic neuronal inhibition concern activation and functional properties of extrasynaptic GABA(A) receptors (GABARex) present on neurones. Extrasynaptic receptors are exposed to submicromolar GABA concentrations and may modulate the overall excitability of neurones and neuronal networks. Here, we examined GABA-activated single-channel currents in dentate gyrus granule neurones in rat hippocampal slices. We activated three types (I, II, III) of GABARex channels by nanomolar GABA concentrations (EC50 I: 27 +/- 12; II: 4 +/- 3; III: 43 +/- 19 nM). The channels opened after a delay and the single-channel conductance was graded (gamma(max) I: 61 +/- 3; II: 85 +/- 8, III: 40 +/- 3 pS). The channels were differentially modulated by 1 mu M diazepam, 200 nM zolpidem, 1 mu M flumazenil and 50 nM THDOC (3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one), consistent with the following minimal subunit composition of GABARex I alpha(1)beta gamma(2), GABARex II alpha(4)beta gamma(2) and GABARex III alpha beta delta channels.},
  author       = {Lindquist, Catarina and Birnir, Bryndis},
  issn         = {1471-4159},
  keyword      = {single-channel current,patch-clamp,GABA channels,hippocampus,tonic,inhibition},
  language     = {eng},
  month        = {03},
  number       = {5},
  pages        = {1349--1356},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Neurochemistry},
  title        = {Graded response to GABA by native extrasynaptic GABA(A) receptors},
  url          = {http://dx.doi.org/10.1111/j.1471-4159.2006.03811.x},
  volume       = {97},
  year         = {2006},
}