Chicken GABAA receptor β4 subunits form robust homomeric GABA-gated channels in Xenopus oocytes

Liu, Sin-Chieh; Parent, Lucie; Harvey, Robert J.; Darlison, Mark G.; Eugene, Jr M. Barnes

Abstract

Chicken {GABAA} receptor β4L and β4S subunits were expressed in Xenopus oocytes by cRNA injection. Oocytes expressing either β4 subunit alone or in combination with the chicken α1 subunit were studied using the two-electrode voltage-clamp technique. Both the β4L and β4S subunits form homomeric GABA-gated Cl− channels with similar efficiencies. In comparison, oocytes expressing either the chicken α1 or β2S polypeptide show no or barely detectable {GABA} responses, as reported by others for most single-subunit vertebrate {GABAA} receptors. The GABA-gated currents due to the β4L-subunit homomer were not affected by the presence of actinomycin D during cRNA expression, indicating that nascent oocyte polypeptides are not required for channel formation. The homomeric β4L-subunit receptors show high affinity for {GABA} with an {EC50} value of 4.3±0.4 μM and a Hill coefficient of 1.1±0.1 (n=6). In response to {GABA} application at the {EC25} value, currents elicited from the β4L-subunit receptor are enhanced by 50 μM pentobarbital (110±10%, n=3) and 10 μM loreclezole (60±3%, n=3), inhibited by 10 μM picrotoxinin (93±3%, n=3), but not affected by 1 μM diazepam. These properties are similar to those found for oocytes expressing heteromeric chicken α1β4L and α1β2S receptors. Since the β subunits of {GABAA} receptors provide essential determinants for receptor assembly and subcellular localization, homomeric β4-subunit receptors are a useful model system for further study of the structure and function of {GABAA} receptors.

Citation

Liu, S.-C., Parent, L., Harvey, R. J., Darlison, M. G., & Eugene, J. M. B. (1998). Chicken GABAA receptor β4 subunits form robust homomeric GABA-gated channels in Xenopus oocytes. European Journal of Pharmacology, 354(2-3), 253-259. https://doi.org/10.1016/S0014-2999%2898%2900453-1

• Journal Article Type: Article
• Acceptance Date: Jun 12, 1998
• Publication Date: Aug 7, 1998
• Deposit Date: Jul 26, 2016
• Journal: European Journal of Pharmacology
• Print ISSN: 0014-2999
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 354
• Issue: 2-3
• Pages: 253-259
• DOI: https://doi.org/10.1016/S0014-2999%2898%2900453-1
• Keywords: Allosteric modulation, β4 subunit, chicken; GABAA receptor, homomeric receptor, Xenopus oocyte
• Public URL: http://researchrepository.napier.ac.uk/Output/316333