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Allosteric plasticity of GABAA receptors

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After developing of pentylenetetrazole kindling (20mg/kg, daily, 24 day), PTZ causes seizures, interacting with the PCT site of GABAAR and allosterically reduces the activity of GABA and benzodiazepines (BDZ) sites. BZD site density decreases by 20% (80% relative to control) without changes in binding ...

After developing of pentylenetetrazole kindling (20mg/kg, daily, 24 day), PTZ causes seizures, interacting with the PCT site of GABAAR and allosterically reduces the activity of GABA and benzodiazepines (BDZ) sites. BZD site density decreases by 20% (80% relative to control) without changes in binding affinity. The reaction is kept 48 hours, after 7 days returns to baseline. After 6 months in kindling rats BZD site density decreases to 50%. A single administration of PTZ 30mg/kg completely restores the intensity of seizures, increases the density of BDZ site to 80% of control (20% reduction from control) without changing the affinity. The seizures of this age animals are accompanied by decrease in the density and affinity of the BDS site. Such differences biophysical characteristics receptor binding with ligand may be linked by two GABAAR subtypes with different subunit composition. We assume that this process can be described by trafficking of GABAAR.
Kindling development formed GABAAR specific cluster. It is shown that 80% of the native GABAAR sensitive to diazepam and contain α1, α2, α3, α5 subunits in the compositions. We have calculated that 20% reduction of site density may occur if 16% of GABAAR replace their α subunit on the α4 and α5. Appearance of GABAAR new specific cluster associated with modification of gene expression
Normalization of the receptor response after 7 days is associated with the internalization of a specific cluster GABAAR, storage into endosomes and recycling by reminder. This mechanism of long-term storage of information in the processes of learning, memory and kindling and other long-lasting processes. Convulsions are involved in the learning process because they induce dissociative learning and cause retrograde amnesia, memory is restored by reminder.
We welcome manuscripts (experimental and review) for the modification of gene expression and expression of new subunits, modification of GABAAR subunit composition and the formation of specific clusters of GABAAR. Features of trafficking of GABAAR under the influence of an external and internal signals, the processes of learning and memory, formation convulsive states, drug and alcohol addiction, and other long-lasting reactions. We will be pleased to receive manuscripts on interactive regulation activity of GABA, AMPA, NMDA, DA and other receptors, integration of these receptors activity, and its long-lasting storage by modifying of gene expression and trafficking of receptors. The transduction signals induction by sites of the GABAAR. Correlation of phosphorylation and dephosphorylation processes, the ratio of the efficiency of the protein kinases in the regulation and the integration of the receptors activity. Self-regulation activity of GABA, NMDA, DA and other receptors.


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