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We examined the effects of TRH on GABAergic transmission in the hippocampus and found that TRH increased the frequency of GABA<jats:sub>A<\/jats:sub> receptor\u2010mediated spontaneous IPSCs in each region of the hippocampus but had no effects on miniature IPSCs or evoked IPSCs. TRH increased the action potential firing frequency recorded from GABAergic interneurons in CA1 stratum radiatum and induced membrane depolarization suggesting that TRH increases the excitability of interneurons to facilitate GABA release. TRH\u2010induced inward current had a reversal potential close to the K<jats:sup>+<\/jats:sup> reversal potential suggesting that TRH inhibits resting K<jats:sup>+<\/jats:sup> channels. The involved K<jats:sup>+<\/jats:sup> channels were sensitive to Ba<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup> but resistant to other classical K<jats:sup>+<\/jats:sup> channel blockers, suggesting that TRH inhibits the two\u2010pore domain K<jats:sup>+<\/jats:sup> channels. Because the effects of TRH were mediated via G\u03b1<jats:sub>q\/11<\/jats:sub>, but were independent of its known downstream effectors, a direct coupling may exist between G\u03b1<jats:sub>q\/11<\/jats:sub> and K<jats:sup>+<\/jats:sup> channels. Inhibition of the function of dynamin slowed the desensitization of TRH responses. TRH inhibited seizure activity induced by Mg<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup> deprivation, but not that generated by picrotoxin, suggesting that TRH\u2010mediated increase in GABA release contributes to its anti\u2010epileptic effects. Our results demonstrate a novel mechanism to explain some of the hippocampal actions of TRH.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.118141","type":"journal-article","created":{"date-parts":[[2006,9,22]],"date-time":"2006-09-22T00:42:51Z","timestamp":1158885771000},"page":"497-511","source":"Crossref","is-referenced-by-count":60,"title":["Thyrotropin\u2010releasing hormone increases GABA release in rat hippocampus"],"prefix":"10.1113","volume":"577","author":[{"given":"Pan\u2010Yue","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee\u2010Sup","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saobo","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.65.2.381"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/mi.3.4.205"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1992.68.5.1733"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)90527-4"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1408-04.2004"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3198-04.2005"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507710103"},{"key":"e_1_2_5_9_1","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1210\/endo.134.5.8156928","article-title":"Calcium\/calmodulin\u2010dependent protein kinase\u2010II activation in rat pituitary cells in the presence of thyrotropin\u2010releasing hormone and dopamine","volume":"134","author":"Cui ZJ","year":"1994","journal-title":"Endocrinology"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.104463"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(85)80126-1"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01077.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1993.tb00922.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1996.76.1.175"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.017590"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.2004.01266.x"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20001211)428:2<319::AID-CNE10>3.0.CO;2-9"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600234"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.6.10.1673"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9268"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/38508"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.13.9340"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.78.3.1726"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(01)00321-6"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100207200"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.034017"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-03-00868.1998"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.5.F793"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90119-5"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.05-01-00167.1985"},{"key":"e_1_2_5_31_1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1523\/JNEUROSCI.05-02-00551.1985","article-title":"Thyrotropin\u2010releasing hormone (TRH) receptors. 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