Characterization of GAVA_A receptor-mediated ³⁶chloride uptake in rat brain synaptoneurosomes

γ-aminobutyric acid (GABA) receptor-mediated ³⁶chloride (³⁶Cl^-) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated ³⁶Cl^- uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA> piperidine-4-sulfonic acid (P4S)>4, 5, 6, 7-tetrahydroisoxazolo-[5, 4-c]pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS) >taurine. Both P4S and 3APS behaved as partial agonists, while the GABA_B agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated ³⁶Cl^- uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated ³⁶Cl^- uptake was also dependent on the anion present in the media. The muscimol response varied in media containing the following anions: Br^->Cl^->N0₃^->I^->SCN^->C₃H₅00^->C104^->F^-, consistent with the relative anion permeability through GABA receptorgated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl^- channel.