{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:14:54Z","timestamp":1790763294212,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"3-4","license":[{"start":{"date-parts":[[2006,9,5]],"date-time":"2006-09-05T00:00:00Z","timestamp":1157414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Aims:\u2002<\/jats:bold> We compared the antagonistic effects of state\u2010dependent gamma\u2010aminobutyric acid A (GABA<jats:sub>A<\/jats:sub>) receptor blockers picrotoxin, Zn<jats:sup>2+<\/jats:sup> and pregnenolone sulphate (PS) on GABA\u2010 and pentobarbital\u2010activated currents in recombinant <jats:italic>rat<\/jats:italic> GABA<jats:sub>A<\/jats:sub> receptors in <jats:italic>Xenopus<\/jats:italic> oocytes.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Experiments were performed with wild type <jats:italic>rat<\/jats:italic><jats:italic>\u03b1<\/jats:italic>1<jats:italic>\u03b2<\/jats:italic>2<jats:italic>\u03b3<\/jats:italic>2L and <jats:italic>\u03b1<\/jats:italic>1<jats:italic>\u03b2<\/jats:italic>2 receptors, mutants <jats:italic>\u03b1<\/jats:italic>1V256S<jats:italic>\u03b2<\/jats:italic>2<jats:italic>\u03b3<\/jats:italic>2L and <jats:italic>\u03b1<\/jats:italic>1<jats:italic>\u03b2<\/jats:italic>2A252S<jats:italic>\u03b3<\/jats:italic>2L receptors by the two\u2010electrode voltage\u2010clamp technique.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> In contrast to respective 3840\u2010 and 56\u2010fold increases in Zn<jats:sup>2+<\/jats:sup> potencies to inhibit GABA\u2010 and pentobarbital\u2010activated currents in the <jats:italic>\u03b1<\/jats:italic>1<jats:italic>\u03b2<\/jats:italic>2 receptor, the corresponding potencies of PS remained unchanged in comparison with the <jats:italic>\u03b1<\/jats:italic>1<jats:italic>\u03b2<\/jats:italic>2<jats:italic>\u03b3<\/jats:italic>2L receptor. A homologous mutation of the residue at 2\u2032 position closest to the cytoplasmic end of the M<jats:sub>2<\/jats:sub> helix to <jats:italic>serine<\/jats:italic> on both <jats:italic>\u03b1<\/jats:italic>1 and <jats:italic>\u03b2<\/jats:italic>2 subunit, <jats:italic>\u03b1<\/jats:italic>1V256S and <jats:italic>\u03b2<\/jats:italic>2A252S, abolished the inhibition of GABA<jats:sub>A<\/jats:sub> receptor by PS. In comparison with the wild type <jats:italic>\u03b1<\/jats:italic>1<jats:italic>\u03b2<\/jats:italic>2<jats:italic>\u03b3<\/jats:italic>2L receptor, mutants <jats:italic>\u03b1<\/jats:italic>1V256S<jats:italic>\u03b2<\/jats:italic>2<jats:italic>\u03b3<\/jats:italic>2L and <jats:italic>\u03b1<\/jats:italic>1<jats:italic>\u03b2<\/jats:italic>2A252S<jats:italic>\u03b3<\/jats:italic>2L receptors did not affect the Zn<jats:sup>2+<\/jats:sup> inhibition. Furthermore, a significant increase in GABA potency was observed in the mutant <jats:italic>\u03b1<\/jats:italic>1V256S<jats:italic>\u03b2<\/jats:italic>2<jats:italic>\u03b3<\/jats:italic>2L receptor (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05), but not the mutant <jats:italic>\u03b1<\/jats:italic>1<jats:italic>\u03b2<\/jats:italic>2A252S<jats:italic>\u03b3<\/jats:italic>2L receptor compared with the wild type receptor.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Pregnenolone sulphate was a <jats:italic>\u03b3<\/jats:italic>2\u2010subunit independent inhibitor in the GABA<jats:sub>A<\/jats:sub> receptor, whereas the Zn<jats:sup>2+<\/jats:sup> antagonism was profoundly influenced by the <jats:italic>\u03b3<\/jats:italic>2\u2010subunit. It is likely that the 2\u2032 residue closest to the N\u2010terminus of the protein at M<jats:sub>2<\/jats:sub> helix on both <jats:italic>\u03b1<\/jats:italic>1 and <jats:italic>\u03b2<\/jats:italic>2 subunit are critical to the inhibitory actions of PS and the function of Cl<jats:sup>\u2212<\/jats:sup> channels. These results are consistent with the hypothesis that PS behaves as a Cl<jats:sup>\u2212<\/jats:sup> channel blocker that does not share with Zn<jats:sup>2+<\/jats:sup>, the coincident channel property in the GABA<jats:sub>A<\/jats:sub> receptors.<\/jats:p>","DOI":"10.1111\/j.1748-1716.2006.01617.x","type":"journal-article","created":{"date-parts":[[2006,9,5]],"date-time":"2006-09-05T13:40:34Z","timestamp":1157463634000},"page":"153-162","source":"Crossref","is-referenced-by-count":15,"title":["Pregnenolone sulphate and Zn<sup>2+<\/sup> inhibit recombinant <i>rat<\/i> GABA<sub>A<\/sub> receptor through different channel property"],"prefix":"10.1111","volume":"188","author":[{"given":"M.\u2010D.","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"B\u00e4ckstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,9,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1986.sp016246"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0673e.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(02)00109-0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5247.369"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-17-05415.1996"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00749-X"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(90)90337-F"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.043810"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80962-9"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.15.10100"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(08)60279-2"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.77.4.1924"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.609bv.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.11.020"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/87425"},{"key":"e_1_2_7_17_1","first-page":"1839","article-title":"Rupture of the right pulmonary artery aneurysm after shunt operation of tetralogy of Fallot","volume":"34","author":"Hoshino K.","year":"1986","journal-title":"Nippon Kyobu Geka Gakkai Zasshi"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1030"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/324670a0"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(96)00089-5"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.639bs.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(96)00035-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(86)90259-1"},{"key":"e_1_2_7_24_1","first-page":"267","article-title":"Noncompetitive inhibition of gamma\u2010aminobutyric acidA channels by Zn","volume":"39","author":"Legendre P.","year":"1991","journal-title":"Mol Pharmacol"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90024-3"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/321406a0"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.5.1932"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(98)00172-5"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-10-03571.2000"},{"key":"e_1_2_7_30_1","first-page":"181","article-title":"Structure and pharmacology of gamma\u2010aminobutyric acidA receptor subtypes","volume":"47","author":"Sieghart W.","year":"1995","journal-title":"Pharmacol Rev"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019020"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12984.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-7971-3_41"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12337.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-08-02728.1997"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(97)00041-1"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-09-03366.2002"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/328640a0"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374264"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020231"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1748-1716.2006.01617.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1748-1716.2006.01617.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T16:11:29Z","timestamp":1693498289000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1748-1716.2006.01617.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,12]]},"references-count":39,"journal-issue":{"issue":"3-4","published-print":{"date-parts":[[2006,11]]}},"alternative-id":["10.1111\/j.1748-1716.2006.01617.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1748-1716.2006.01617.x","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9,12]]}}}