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1. The aim of this study was to define the biophysical properties contributed by the gamma2 subunit to native single GABAA receptors. 2. Single-channel activity was recorded from neurones of wild-type (gamma2+/+) mice and compared with that from mice which were heterozygous (gamma2+/-) or homozygous (gamma2-/-) for a targeted disruption in the gamma2 subunit gene of the GABAA receptor. Unitary currents were evoked by low concentrations of GABA (0.5-5 microM) in membrane patches from acutely isolated dorsal root ganglion (DRG) neurones (postnatal day 0) and by 1 microM GABA in patches from embryonic hippocampal neurones which were cultured for up to 3 weeks. 3. GABAA receptors from DRG and hippocampal neurones of gamma2+/+ and gamma2+/- mice displayed predominantly a conductance state of 28 pS and less frequently 18 and 12 pS states. In gamma2-/- mice, conductance states mainly of 12 pS and less frequently of 24 pS were found. 4. The mean open duration of the 28 pS state in gamma2+/+ GABAA receptors (1.5-2.6 ms) was substantially longer than for the 12 pS state of gamma2-/- GABAA receptors (0.9-1.2 ms) at all GABA concentrations. For gamma2+/+ and gamma2-/- channels, the mean open duration was increased at higher GABA concentrations. 5. Open duration frequency distributions of 28 and 12 pS receptors revealed the existence of at least three exponential components. Components with short mean durations declined and components with long mean durations increased in relative frequency at higher GABA concentration indicating at least two binding sites of GABA per 28 and 12 pS receptor. 6. Shut time frequency distributions revealed at least four exponential components of which two were identified as intraburst components in 28 pS and one in 12 pS GABAA receptors. 7. The mean burst duration and the mean number of openings per burst increased in 28 and 12 pS GABAA receptors with increasing GABA concentration. At least two burst types were identified: simple bursts consisting of single openings and complex bursts of five to six openings in 28 pS but only two to three openings in 12 pS GABAA receptors. 8. We conclude that the gamma2 subunit enhances the efficacy of GABA by determining open conformations of high conductance and long lifetime, and by prolonging the time receptors remain in the activated bursting state.
Pubmed ID: 10944167 RIS Download
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THIS RESOURCE IS NO LONGER IN SERVICE. Documented on March 17, 2022. A large-scale database of genetics and genomics data associated to a web-interface and a set of methods and algorithms that can be used for mining the data in it. The database contains two categories of single nucleotide polymorphism (SNP) annotations: # Physical-based annotation where SNPs are categorized according to their position relative to genes (intronic, inter-genic, etc.) and according to linkage disequilibrium (LD) patterns (an inter-genic SNP can be annotated to a gene if it is in LD with variation in the gene). # Functional annotation where SNPs are classified according to their effects on expression levels, i.e. whether they are expression quantitative trait loci (eQTLs) for that gene. SCAN can be utilized in several ways including: (i) queries of the SNP and gene databases; (ii) analysis using the attached tools and algorithms; (iii) downloading files with SNP annotation for various GWA platforms. . eQTL files and reported GWAS from NHGRI may be downloaded.
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