Graded response to GABA by native extrasynaptic GABA(A) receptors
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/156126
- author
- Lindquist, Catarina LU and Birnir, Bryndis LU
- organization
- publishing date
- 2006-03-29
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: GABA Channels in Physiology and Pharmacology (013241570)
- id
- 85a60365-6054-4bdf-99c9-138aa6e29607 (old id 156126)
- date added to LUP
- 2016-04-01 16:13:35
- date last changed
- 2022-05-08 08:40:04
@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}}, keywords = {{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 = {{https://lup.lub.lu.se/search/files/4608197/625435.pdf}}, doi = {{10.1111/j.1471-4159.2006.03811.x}}, volume = {{97}}, year = {{2006}}, }