ININFA   02677
INSTITUTO DE INVESTIGACIONES FARMACOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
GABA-induced regulation of allosteric interactions between GABA and benzodiazepine sites in rat neocortical neurons
Autor/es:
M. L. GUTIÉRREZ; M- C. FERRERI; M. C. GRAVIELLE
Lugar:
Huerta Grande
Reunión:
Congreso; Reunión Anual de la Sociedad Argentina de Neurociencias; 2012
Institución organizadora:
Sociedad Argentina de Neurociencias
Resumen:
We have previously showed that a brief exposure of rat neocortical neurons to GABA (t1/2 3.2 min) produces hours later (t1/2 12 hs) an uncoupling of the interaction between GABA and benzodiazepine sites, without changes in GABAA receptor number. Since the strength of allosteric coupling depends on the α subunit subtype present in the GABAA receptor (rank order: α3 > α1/5), the aim of this work was to determine whether uncoupling is produced by alterations in the receptor subunit combination. To this end, neocortical cultures were incubated with GABA for 10 min and cells were collected 48 h later. Receptors were immunoprecipitated with an antibody anti- γ2 subunits, that are present in most of the receptors, and analyzed by western blot. We observed a decrease in α3γ2 and an increase in α5γ2 receptor number. The number of α1γ2 receptors remained constant. We next performed a biotinylation assay followed by western blot to measure the cell surface expression of α3 and α5 subunits. GABA induced a reduction in plasma membrane levels of α3 but no significant change in surface expression of α5. These results suggest that GABA-induced uncoupling involves a change in the subunit composition of GABAA receptors, resulting in a reduced coupling between GABA and benzodiazepine binding sites.