{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T01:49:52Z","timestamp":1775353792290,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":4385,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1997,2]]},"abstract":"\n\nRadioligand binding and patch\u2010clamp techniques were used to study the actions of \u03b3\u2010aminobutyric acid (GABA) and the general anaesthetics propofol (2,6\u2010diisopropylphenol), pentobarbitone and 5\u03b1\u2010pregnan\u20103\u03b1\u2010ol\u201020\u2010one on rat \u03b11 and \u03b23 GABAA<\/jats:sub> receptor subunits, expressed either alone or in combination.<\/jats:p><\/jats:list-item>\nMembranes from HEK293 cells after transfection with \u03b11 cDNA did not bind significant levels of [35<\/jats:sup>S]\u2010tert\u2010butyl bicyclophosphorothionate ([35<\/jats:sup>S]\u2010TBPS) (<0.03 pmol mg\u22121<\/jats:sup> protein). GABA (100 \u03bcm<\/jats:sc>) applied to whole\u2010cells transfected with \u03b11 cDNA and clamped at \u221260 mV, also failed to activate discernible currents.<\/jats:p><\/jats:list-item>\nThe membranes of cells expressing \u03b23 cDNAs bound [35<\/jats:sup>S]\u2010TBPS (\u223c1 pmol mg\u22121<\/jats:sup> protein). However, the binding was not influenced by GABA (10 nm<\/jats:sc>\u2013100 \u03bcm<\/jats:sc>). Neither GABA (100 \u03bcm<\/jats:sc>) nor picrotoxin (10 \u03bcm<\/jats:sc>) affected currents recorded from cells expressing \u03b23 cDNA, suggesting that \u03b23 subunits do not form functional GABAA<\/jats:sup> receptors or spontaneously active ion channels.<\/jats:p><\/jats:list-item>\nGABA (10 nm<\/jats:sc>\u2013100 \u03bcm<\/jats:sc>) modulated [35<\/jats:sup>S]\u2010TBPS binding to the membranes of cells transfected with both \u03b11 and \u03b23 cDNAs. GABA (0.1 \u03bcm<\/jats:sc>\u20131 mm<\/jats:sc>) also dose\u2010dependently activated inward currents with an EC50<\/jats:sub> of 9 \u03bcm<\/jats:sc> recorded from cells transfected with \u03b11 and \u03b23 cDNAs, clamped at \u221260 mV.<\/jats:p><\/jats:list-item>\nPropofol (10 nm<\/jats:sc>\u2013100 \u03bcm<\/jats:sc>), pentobarbitone (10 nm<\/jats:sc>\u2013100 \u03bcm<\/jats:sc>) and 5\u03b1\u2010pregnan\u20103\u03b1\u2010ol\u201020\u2010one (1 nm<\/jats:sc>\u201330\u2002\u03bcm<\/jats:sc>) modulated [35<\/jats:sup>S]\u2010TBPS binding to the membranes of cells expressing either \u03b11\u03b23 or \u03b23 receptors. Propofol (100 \u03bcm<\/jats:sc>), pentobarbitone (1 mm<\/jats:sc>) and 5\u03b1\u2010pregnan\u20103\u03b1\u2010ol\u201020\u2010one (10 \u03bcm<\/jats:sc>) also activated currents recorded from cells expressing \u03b11\u03b23 receptors.<\/jats:p><\/jats:list-item>\nPropofol (1 \u03bcm<\/jats:sc>\u20131 mm<\/jats:sc>) and pentobarbitone (1 mm<\/jats:sc>) both activated currents recorded from cells expressing \u03b23 homomers. In contrast, application of 5\u03b1\u2010pregnan\u20103\u03b1\u2010ol\u201020\u2010one (10 \u03bcm<\/jats:sc>) failed to activate detectable currents.<\/jats:p><\/jats:list-item>\nPropofol (100 \u03bcm<\/jats:sc>)\u2010activated currents recorded from cells expressing either \u03b11\u03b23 or \u03b23 receptors reversed at the C1\u2212<\/jats:sup> equilibrium potential and were inhibited to 34\u00b113% and 39\u00b110% of control, respectively, by picrotoxin (10 \u03bcm<\/jats:sc>). 5\u03b1\u2010Pregnan\u20103\u03b1\u2010ol\u201020\u2010one (100 nm<\/jats:sc>) enhanced propofol (100 \u03bcm<\/jats:sc>)\u2010evoked currents mediated by \u03b11\u03b23 receptors to 1101\u00b1299% of control. In contrast, even at high concentration 5\u03b1\u2010pregnan\u20103\u03b1\u2010ol\u201020\u2010one (10 \u03bcm<\/jats:sc>) caused only a modest facilitation (to 128\u00b112% of control) of propofol (100 \u03bcm<\/jats:sc>)\u2010evoked currents mediated by \u03b23 homomers.<\/jats:p><\/jats:list-item>\nPropofol (3\u2013100 \u03bcm<\/jats:sc>) activated \u03b11\u03b23 and \u03b23 receptors in a concentration\u2010dependent manner. For both receptor combinations, higher concentrations of propofol (300 \u03bcm<\/jats:sc> and 1 mm<\/jats:sc>) caused a decline in current amplitude. This inhibition of receptor function reversed rapidly during washout resulting in a \u2018surge\u2019 current on cessation of propofol (300 \u03bcm<\/jats:sc> and 1 mm<\/jats:sc>) application. Surge currents were also evident following pentobarbitone (1 mm<\/jats:sc>) application to cells expressing either receptor combination. By contrast, this phenomenon was not apparent following applications of 5\u03b1\u2010pregnan\u20103\u03b1\u2010ol\u201020\u2010one (10 \u03bcm<\/jats:sc>) to cells expressing \u03b11\u03b23 receptors.<\/jats:p><\/jats:list-item>\nThese observations demonstrate that rat \u03b23 subunits form homomeric receptors that are not spontaneously active, are insensitive to GABA and can be activated by some general anaesthetics. Taken together, these data also suggest similar sites on GABAA<\/jats:sub> receptors for propofol and barbiturates, and a separate site for the anaesthetic steroids.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>British Journal of Pharmacology<\/jats:italic> (1997) 120<\/jats:bold>, 899\u2013909; doi:10.1038\/sj.bjp.0700987<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0700987","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T16:10:42Z","timestamp":1156522242000},"page":"899-909","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Modulation by general anaesthetics of rat GABAA<\/sub> receptors comprised of \u03b1<\/i>1\u03b2<\/i>3 and \u03b2<\/i>3 subunits expressed in human embryonic kidney 293 cells"],"prefix":"10.1111","volume":"120","author":[{"given":"Paul A","family":"Davies","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewen F","family":"Kirkness","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim G","family":"Hales","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15903.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/366565a0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-04-01429.1993"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15439.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2845583"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016493"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.5.14.1661244"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199603220-00023"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00175035"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.1.89"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/367607a0"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12479.x"},{"key":"e_1_2_6_14_1","first-page":"295","volume-title":"The Pharmacological Basis of Anesthesiology, Basic Science and Clinical Applications","author":"Hales T.G.","year":"1994"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199310000-00021"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199410000-00026"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(94)90082-5"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb12866.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb13310.x"},{"key":"e_1_2_6_20_1","first-page":"962","article-title":"Modulation of the GABAA receptor by propofol is independent of the \u03b3 subunit","volume":"274","author":"Jones M.V.","year":"1995","journal-title":"J. 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