Functional pharmacology of GABA(A) receptors containing the chicken brain gamma 4 subunit

The functional pharmacology of receptors composed of the chicken brain GABA (A) receptor gamma4 subunit and the mammalian GABA(A) receptor alpha3 and b eta2 subunits was studied by heterologous expression in Xenopus laevis oocy tes using the two electrode voltage-clamp technique. GABA-evoked currents h ad an EC50 of 180 +/- 30 muM. Responses were blocked by the competitive and non-competitive GABA(A) receptor antagonists, bicuculline methochloride an d picrotoxin. Sodium pentobarbital reversibly potentiated the current sever al-fold, and Zn2+ ions blocked the current with high potency (IC50 = 20 muM ). GABA-evoked currents were potentiated by the benzodiazepine site full ag onists flunitrazepam and triazolam and less by the partial agonists abecarn il and bretazenil. The inverse agonists methyl-beta -carboline-3-carboxylat e (beta -CCM) and methyl 6,7-dimethoxy-4-ethyl-beta -carboline-3-carboxylat e (DMCM) reduced the current. However, the imidazobenzodiazepine Ro 15-4513 , which acts as an inverse agonist at mammalian alphax betay gamma2 GABA(A) receptors (where x = 1, 2, 3 or 5, and y = 1, 2 or 3), acted as a positive agonist at the gamma4 subunit-containing receptors. (C) 2001 Elsevier Scie nce B.V. All rights reserved.