Characterization and differential regulation of GABAA and benzodiazepine receptors in rat neocortex.

We have characterized the gamma-aminobutyric acid-A (GABAA) and benzodiazepine (BZ) receptors in in vitro living slices of adult rat neocortex using [3H]SR95531, a GABAA antagonist, and [3H]flunitrazepam (FNZ), a BZ ligand. [3H]SR95531 labelled a single population of GABAA receptors with a Bmax of 1030.7 fmol/mg protein and a Kd of 43.5 nM. [3H]FNZ also labelled a single binding site with a Bmax of 4239 fmol/mg protein and a Kd of 22 nM. The GABAA receptor labelled using [3H]SR95531 could be down-regulated by 2 h preincubations in GABA and the GABAA agonist muscimol (8% and 11%, respectively). Increases in cellular electrical activity induced by a combination of veratridine and glutamate led to an average increase in GABAA receptor number of 58%. The BZ binding site labelled with [3H]FNZ was down-regulated by clonazepam (-55%), increased by GABA (+17%), but not altered by changes in electrical activity. The present results demonstrate the rapid differential regulation of a ligand-gated receptor by agonist stimulation or increases in bioelectric activity. Such regulation may provide clues to the nature of the modifications which occur following changes in cellular activity in the cortex.