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Graded response to GABA by native extrasynaptic GABA A receptors
Author(s) -
Lindquist Catarina E. L.,
Birnir Bryndis
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03811.x
Subject(s) - gabaa receptor , hippocampal formation , neuroscience , inhibitory postsynaptic potential , neurotransmission , dentate gyrus , chemistry , tonic (physiology) , receptor , biology , biochemistry
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 (EC 50 I: 27 ± 12; II: 4 ± 3; III: 43 ± 19 n m ). The channels opened after a delay and the single‐channel conductance was graded (γ max I: 61 ± 3; II: 85 ± 8, III: 40 ± 3 pS). The channels were differentially modulated by 1 µ m diazepam, 200 n m zolpidem, 1 µ m flumazenil and 50 n m THDOC (3α, 21‐dihydroxy‐5α‐pregnan‐20‐one), consistent with the following minimal subunit composition of GABARex I α 1 βγ 2 , GABARex II α 4 βγ 2 and GABARex III αβδ channels.