{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:15:11Z","timestamp":1791407711882,"version":"4.3.3"},"reference-count":21,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,5,30]]},"abstract":"<jats:p>\n                    The mRNA levels of NKCC1, an inwardly directed Na\n                    <jats:sup>+<\/jats:sup>\n                    , K\n                    <jats:sup>+<\/jats:sup>\n                    -2Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter that facilitates the accumulation of intracellular Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    , and of KCC2, an outwardly directed K\n                    <jats:sup>+<\/jats:sup>\n                    -Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter that extrudes Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    , were studied in surgically resected brain specimens from drug-resistant temporal lobe (TL) epilepsy (TLE) patients. Quantitative RT-PCR analyses of the mRNAs extracted from the human TLE-associated brain regions revealed an up-regulation of NKCC1 mRNA and a down-regulation of KCC2 mRNA in the hippocampal subiculum, compared with the hippocampus proper or the TL neocortex, suggesting an abnormal transcription of Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    transporters in the TLE subiculum. In parallel experiments, cell membranes isolated from the same TLE-associated brain regions were injected into\n                    <jats:italic>Xenopus<\/jats:italic>\n                    oocytes that rapidly incorporated human GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors into their surface membrane. The GABA currents elicited in oocytes injected with membranes from the subiculum had a more depolarized reversal potential (\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    ) compared with the hippocampus proper or the neocortex. The NKCC1 blocker bumetanide or a temperature decrease of 10\u00b0C shifted the GABA-current\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    more negative in oocytes injected with membranes from TLE hippocampal subiculum, matching the\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    of TL neocortex-injected oocytes. We conclude that the anomalous expression of both Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    transporters, KCC1 and NKCC2, in TLE hippocampal subiculum probably causes altered Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    transport in the \u201cepileptic\u201d neurons, as revealed in the microtransplanted\n                    <jats:italic>Xenopus<\/jats:italic>\n                    oocytes, and renders GABA aberrantly \u201cexciting,\u201d a feature that may contribute to the precipitation of epileptic seizures.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0602979103","type":"journal-article","created":{"date-parts":[[2006,5,18]],"date-time":"2006-05-18T20:54:14Z","timestamp":1147985654000},"page":"8465-8468","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":287,"title":["Anomalous levels of Cl\n                    <sup>\u2212<\/sup>\n                    transporters in the hippocampal subiculum from temporal lobe epilepsy patients make GABA excitatory"],"prefix":"10.1073","volume":"103","author":[{"given":"E.","family":"Palma","sequence":"first","affiliation":[{"name":"*Istituto Pasteur, Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza Biologia e Medicina Molecolare, Universit\u00e0 di Roma \u201cLa Sapienza,\u201d Piazzale A. Moro 5, 00185 Rome, Italy;"},{"name":"Neuromed Istituto di Ricovero e Cura a Carattere Scientifico, Via Atinese 18, 86077 Pozzilli, Italy;"},{"name":"Istituto di Medicina e Scienza dello Sport, CONI, Via dei Campi Sportivi LG, 00197 Rome, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Amici","sequence":"additional","affiliation":[{"name":"*Istituto Pasteur, Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza Biologia e Medicina Molecolare, Universit\u00e0 di Roma \u201cLa Sapienza,\u201d Piazzale A. Moro 5, 00185 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Sobrero","sequence":"additional","affiliation":[{"name":"*Istituto Pasteur, Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza Biologia e Medicina Molecolare, Universit\u00e0 di Roma \u201cLa Sapienza,\u201d Piazzale A. Moro 5, 00185 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Spinelli","sequence":"additional","affiliation":[{"name":"*Istituto Pasteur, Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza Biologia e Medicina Molecolare, Universit\u00e0 di Roma \u201cLa Sapienza,\u201d Piazzale A. Moro 5, 00185 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Di Angelantonio","sequence":"additional","affiliation":[{"name":"*Istituto Pasteur, Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza Biologia e Medicina Molecolare, Universit\u00e0 di Roma \u201cLa Sapienza,\u201d Piazzale A. Moro 5, 00185 Rome, Italy;"},{"name":"Istituto di Medicina e Scienza dello Sport, CONI, Via dei Campi Sportivi LG, 00197 Rome, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Ragozzino","sequence":"additional","affiliation":[{"name":"*Istituto Pasteur, Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza Biologia e Medicina Molecolare, Universit\u00e0 di Roma \u201cLa Sapienza,\u201d Piazzale A. Moro 5, 00185 Rome, Italy;"},{"name":"Neuromed Istituto di Ricovero e Cura a Carattere Scientifico, Via Atinese 18, 86077 Pozzilli, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mascia","sequence":"additional","affiliation":[{"name":"Neuromed Istituto di Ricovero e Cura a Carattere Scientifico, Via Atinese 18, 86077 Pozzilli, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Scoppetta","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Neurologia 2, Ospedale S. 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