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Incremental conductance levels of GABA A receptors in dopaminergic neurones of the rat substantia nigra pars compacta
Author(s) -
Guyon A.,
Laurent S.,
PaupardinTritsch D.,
Rossier J.,
Eugène D.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0719u.x
Subject(s) - gabaa receptor , substantia nigra , pars compacta , gabaa rho receptor , zolpidem , chemistry , muscimol , biophysics , receptor , allosteric regulation , dopaminergic , protein subunit , neuroscience , biology , pharmacology , biochemistry , dopamine , gene , insomnia
1 Molecular and biophysical properties of GABA A receptors of dopaminergic (DA) neurones of the pars compacta of the rat substantia nigra were studied in slices and after acute dissociation. 2 Single‐cell reverse transcriptase‐multiplex polymerase chain reaction confirmed that DA neurones contained mRNAs encoding for the α3 subunit of the GABA A receptor, but further showed the presence of α4 subunit mRNAs. α2, β1 and γ1 subunit mRNAs were never detected. Overall, DA neurones present a pattern of expression of GABA A receptor subunit mRNAs containing mainly α3/4β2/3γ3. 3 Outside‐out patches were excised from DA neurones and GABA A single‐channel patch‐clamp currents were recorded under low doses (1‐5 μM) of GABA or isoguvacine, a selective GABA A agonist. Recordings presented several conductance levels which appeared to be integer multiples of an elementary conductance of 4‐5 pS. This property was shared by GABA A receptors of cerebellar Purkinje neurones recorded in slices (however, with an elementary conductance of 3 pS). Only the 5‐6 lowest levels were analysed. 4 A progressive change in the distribution of occupancy of these levels was observed when increasing the isoguvacine concentration (up to 10 μM) as well as when adding zolpidem (20‐200 nM), a drug acting at the benzodiazepine binding site: both treatments enlarged the occupancy of the highest conductance levels, while decreasing that of the smallest ones. Conversely, Zn 2+ (10 μM), a negative allosteric modulator of GABA A receptor channels, decreased the occupancy of the highest levels in favour of the lowest ones. 5 These properties of α3/4β2/3γ3‐containing GABA A receptors would support the hypothesis of either single GABA A receptor channels with multiple open states or that of a synchronous recruitment of GABA A receptor channels that could involve their clustering in the membranes of DA neurones.