Functional pharmacology of GABAA receptors containing the chicken brain γ4 subunit

The functional pharmacology of receptors composed of the chicken brain GABAA receptor γ4 subunit and the mammalian GABAA receptor α3 and β2 subunits was studied by heterologous expression in Xenopus laevis oocytes using the two electrode voltage-clamp technique. GABA-evoked currents had an EC50 of 180±30 μM. Responses were blocked by the competitive and non-competitive GABAA receptor antagonists, bicuculline methochloride and picrotoxin. Sodium pentobarbital reversibly potentiated the current several-fold, and Zn2+ ions blocked the current with high potency (IC50 = 20 μM). GABA-evoked currents were potentiated by the benzodiazepine site full agonists flunitrazepam and triazolam and less by the partial agonists abecarnil and bretazenil. The inverse agonists methyl-β-carboline-3-carboxylate (β-CCM) and methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM) reduced the current. However, the imidazobenzodiazepine Ro 15-4513, which acts as an inverse agonist at mammalian αxβyγ2 GABAA receptors (where x = 1, 2, 3 or 5, and y = 1, 2 or 3), acted as a positive agonist at the γ4 subunit-containing receptors. © 2001 Elsevier Science B.V