{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T05:38:02Z","timestamp":1776577082304,"version":"3.51.2"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":120,"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":[[2008,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>\n                      Heterologous expression of \u03b11, \u03b22 and \u03b32S(\u03b31) subunits produces a mixed population of GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptors containing \u03b11\u03b22 or \u03b11\u03b22\u03b32S(\u03b31) subunits. GABA sensitivity (lower in receptors containing \u03b31 or \u03b32S subunits) and the potentiation of GABA\u2010activated chloride currents (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>GABA<\/jats:sub>\n                      ) by benzodiazepines (BZDs) are dependent on \u03b32S(\u03b31) incorporation. A variable \u03b3 subunit incorporation may affect the estimation of\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>GABA<\/jats:sub>\n                      potentiation by BZDs. We propose an approach for estimation of BZD efficiency that accounts for mixed population of \u03b11\u03b22 and \u03b11\u03b22\u03b32S(\u03b31) receptors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>\n                      We investigated the relation between GABA sensitivity (\n                      <jats:italic>EC<\/jats:italic>\n                      <jats:sub>50<\/jats:sub>\n                      ) and BZD modulation by analysing triazolam\u2010, clotiazepam\u2010 and midazolam\u2010induced potentiation of\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>GABA<\/jats:sub>\n                      in\n                      <jats:italic>Xenopus<\/jats:italic>\n                      oocytes under two\u2010microelectrode voltage clamp.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results:<\/jats:title>\n                    <jats:p>\n                      Plotting\n                      <jats:italic>EC<\/jats:italic>\n                      <jats:sub>50<\/jats:sub>\n                      versus BZD\u2010induced shifts of GABA concentration\u2010response curves (\u0394\n                      <jats:italic>EC<\/jats:italic>\n                      <jats:sub>50<\/jats:sub>\n                      (BZD)) of oocytes injected with different amounts of \u03b11, \u03b22 and \u03b32S(\u03b31) cRNA (1:1:1\u20131:1:10) revealed a linear regression between \u03b32S(\u03b31)\u2010mediated reduction of GABA sensitivity (\n                      <jats:italic>EC<\/jats:italic>\n                      <jats:sub>50<\/jats:sub>\n                      ) and \u0394\n                      <jats:italic>EC<\/jats:italic>\n                      <jats:sub>50<\/jats:sub>\n                      (BZD). The slope factors of the regression were always higher for oocytes expressing \u03b11\u03b22\u03b31 subunit receptors (1.8\u00b10.1 (triazolam), 1.6\u00b10.1 (clotiazepam), 2.3\u00b10.2 (midazolam)) than for oocytes expressing \u03b11\u03b22\u03b32S receptors (1.4\u00b10.1 (triazolam), 1.4\u00b10.1 (clotiazepam), 1.3\u00b10.1 (midazolam)). Mutant GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptors (\u03b11\u03b22\u2010R207C\u03b32S) with lower GABA sensitivity showed higher drug efficiencies (slope factors=1.1\u00b10.1 (triazolam), 1.1\u00b10.1 (clotiazepam), 1.2\u00b10.1 (midazolam)).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications:<\/jats:title>\n                    <jats:p>Regression analysis enabled the estimation of BZD efficiency when variable mixtures of \u03b11\u03b22 and \u03b11\u03b22\u03b32S(\u03b31) receptors are expressed and provided new insights into the \u03b32S(\u03b31) dependency of BZD action.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                      (2008)\n                      <jats:bold>155<\/jats:bold>\n                      , 424\u2013433; doi:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.271\">10.1038\/bjp.2008.271<\/jats:ext-link>\n                      ; published online 7 July 2008\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/bjp.2008.271","type":"journal-article","created":{"date-parts":[[2008,7,7]],"date-time":"2008-07-07T06:04:05Z","timestamp":1215410645000},"page":"424-433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Estimating the efficiency of benzodiazepines on GABA\n                    <sub>A<\/sub>\n                    receptors comprising \u03b31 or \u03b32 subunits"],"prefix":"10.1111","volume":"155","author":[{"given":"I","family":"Baburin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Khom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Timin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Hohaus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Sieghart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Hering","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(04)62001-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/366565a0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-04-01429.1993"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-006-0125-y"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0031-6997(24)01363-2","article-title":"International Union of Pharmacology. 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