Functional pharmacology of GABAA receptors containing the chicken brain γ4 subunit

Forster, Ian C.; Harvey, Robert J.; Darlison, Mark G.; Benson, Jack A.

Abstract

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.

• Journal Article Type: Article
• Acceptance Date: Apr 3, 2001
• Online Publication Date: Jul 11, 2001
• Publication Date: 2001-05
• Deposit Date: Jul 26, 2016
• Journal: European Journal of Pharmacology
• Print ISSN: 0014-2999
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 419
• Issue: 1
• Pages: 1-7
• DOI: https://doi.org/10.1016/S0014-2999%2801%2900964-5
• Keywords: Benzodiazepine pharmacology, Electrophysiology, GABAA receptor, Xenopus oocyte, Zn2+ inhibition,
• Public URL: http://researchrepository.napier.ac.uk/Output/316427