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Journal of Neuroscience, Vol 10, 2330-2337, Copyright © 1990 by Society for Neuroscience
Functional characteristics and sites of gene expression of the alpha 1, beta 1, gamma 2-isoform of the rat GABAA receptor
P Malherbe, E Sigel, R Baur, E Persohn, JG Richards and H Mohler
Pharmaceutical Research Department, Hoffmann-La Roche AG, Basel, Switzerland.
GABAA receptors, the major synaptic targets for the neurotransmitter GABA,
constitute gated chloride channels. By their allosteric, drug- induced
modulation, they serve as control elements for the regulation of anxiety,
vigilance, and epileptiform activity. The structural requirements of fully
functional GABAA receptors in the mammalian brain have remained elusive so
far. We report here on the cloning of the gamma 2-subunit cDNA of rat brain
and its functional analysis by coexpression with the alpha 1- and beta
1-subunits in Xenopus oocytes, and on the sites of gene expression of the 3
subunits in the rat brain. The recombinant receptor displayed
GABA-inducible currents (Imax = 6 microA; Ka = 75 microM) which were
allosterically modulated by benzodiazepine receptor ligands (enhancement
and inhibition by diazepam and
methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, respectively).
In the absence of GABA, pentobarbital elicited a maximal current amplitude
similar to that of GABA. A minor population of channels is expressed which
is open in the absence of GABA or pentobarbital. Mapping subunit gene
expression by in situ hybridization histochemistry suggests that the alpha
1-, beta 1-, and gamma 2- subunits are likely receptor constituents in some
neuronal populations, e.g., mitral cells of the olfactory bulb, pyramidal
cells of the hippocampus, and granule cells of the dentate gyrus and
cerebellum.
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