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

ABSTRACT

The functional pharmacology of receptors composed of the chicken brain GABA(A) receptor gamma 4 subunit and the mammalian GABA(A) receptor alpha 3 and beta2 subunits was studied by heterologous expression in Xenopus laevis oocytes using the two electrode voltage-clamp technique. GABA-evoked currents had an EC(50) of 180+/-30 microM. Responses were blocked by the competitive and non-competitive GABA(A) receptor antagonists, bicuculline methochloride and picrotoxin. Sodium pentobarbital reversibly potentiated the current several-fold, and Zn(2+) ions blocked the current with high potency (IC50=20 microM). 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-beta-carboline-3-carboxylate (beta-CCM) and methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) reduced the current. However, the imidazobenzodiazepine Ro 15-4513, which acts as an inverse agonist at mammalian alphaxbetaygamma2 GABA(A) receptors (where x=1, 2, 3 or 5, and y=1, 2 or 3), acted as a positive agonist at the gamma 4 subunit-containing receptors.