{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:57:37Z","timestamp":1791215857973,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2646,"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":[[2001,11]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The influence of membrane cholesterol on some pharmacological properties of the GABA<jats:sub>A<\/jats:sub> receptor was investigated in acutely dissociated rat hippocampal neurones with whole cell patch clamp recording. The cholesterol levels were varied between 56% and 235% control using methyl\u2010\u03b2\u2010cyclodextrin as the cholesterol carrier.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Enrichment of neurones with cholesterol increased the effects of the non\u2010steroidal GABA potentiators propofol, flunitrazepam and pentobarbitone. A similar result was obtained after pre\u2010incubation of neurones with epicholesterol, the 3\u03b1\u2010hydroxy isomer of cholesterol.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In contrast, the effects of the steroidal GABA potentiators pregnanolone and alfaxalone were reduced by cholesterol enrichment, but not by epicholesterol. Depletion of membrane cholesterol increased the potentiation of GABA by pregnanolone and alfaxalone but did not affect the non\u2010steroidal potentiators.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The steroidal antagonist of GABA, pregnenolone sulphate, reduced the maximum response to GABA. This effect, also, was diminished in cholesterol\u2010enriched neurones and enhanced in cholesterol\u2010depleted neurones.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The effects of the cholesterol manipulations that were selective for the steroidal modulators of GABA are suggested to arise from direct interactions between membrane cholesterol and the GABA<jats:sub>A<\/jats:sub> receptor. The separate effects on the non\u2010steroidal potentiators of GABA of cholesterol\u2010enrichment or addition of epicholesterol to the neurones are suggested to be due to changes in membrane fluidity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In view of the likely physiological modulation of GABA<jats:sub>A<\/jats:sub> receptors by endogenous neuroactive steroids and evidence of the <jats:italic>in vivo<\/jats:italic> lability of membrane cholesterol, the present observations may have physiological as well as pharmacological relevance.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>134<\/jats:bold>, 1303\u20131311; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704360\">10.1038\/sj.bjp.0704360<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704360","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:35:16Z","timestamp":1106948116000},"page":"1303-1311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Influence of membrane cholesterol on modulation of the GABA<sub>A<\/sub> receptor by neuroactive steroids and other potentiators"],"prefix":"10.1111","volume":"134","author":[{"given":"T","family":"Sooksawate","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Simmonds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0673e.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/frne.1999.0188"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00179a035"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00352a015"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi963138w"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"e_1_2_7_8_1","first-page":"346","article-title":"Structure\u2010activity relationships for steroid interaction with the \u03b3\u2010aminobutyric acidA receptor complex","volume":"241","author":"HARRISON N.L.","year":"1987","journal-title":"J. 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