{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:33:32Z","timestamp":1791398012970,"version":"4.3.3"},"reference-count":49,"publisher":"Society for Neuroscience","issue":"51","license":[{"start":{"date-parts":[[2008,6,19]],"date-time":"2008-06-19T00:00:00Z","timestamp":1213833600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,12,19]]},"abstract":"<jats:p>\n                    GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptor-mediated inhibition depends on the maintenance of intracellular Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    concentration ([Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    ]\n                    <jats:sub>in<\/jats:sub>\n                    ) at low levels. In neurons in the developing CNS, [Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    ]\n                    <jats:sub>in<\/jats:sub>\n                    is elevated,\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    is depolarizing, and GABA consequently is excitatory. Depolarizing GABAergic synaptic responses may be recapitulated in various neuropathological conditions, including epilepsy. In the present study, rat hippocampal dentate granule cells were recorded using gramicidin perforated patch techniques at varying times (1\u201360 d) after an epileptogenic injury, pilocarpine-induced status epilepticus (STEP). In normal, non-epileptic animals, these strongly inhibited dentate granule cells act as a gate, regulating hippocampal excitation, controlling seizure initiation and\/or propagation. For 2 weeks after STEP, we found that\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    was positively shifted in granule cells. This shift in\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    altered synaptic integration, increased granule cell excitability, and resulted in compromised \u201cgate\u201d function of the dentate gyrus.\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    recovered to control values at longer latencies post-STEP (2\u20138 weeks), when animals had developed epilepsy. During this period of shifted\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    , expression of the Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    extruding K\n                    <jats:sup>+<\/jats:sup>\n                    \/Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    cotransporter, KCC2 was decreased. Application of the KCC2 blocker, furosemide, to control neurons mimicked\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    shifts evident in granule cells post-STEP. Furthermore, post-STEP and furosemide effects interacted occlusively, both on\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>GABA<\/jats:sub>\n                    in granule cells, and on gatekeeper function of the dentate gyrus. This suggests a shared mechanism, reduced KCC2 function. These findings demonstrate that decreased expression of KCC2 persists for weeks after an epileptogenic injury, reducing inhibitory efficacy and enhancing dentate granule cell excitability. This pathophysiological process may constitute a significant mechanism linking injury to the subsequent development of epilepsy.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.4390-07.2007","type":"journal-article","created":{"date-parts":[[2007,12,19]],"date-time":"2007-12-19T13:53:08Z","timestamp":1198072388000},"page":"14012-14022","source":"Crossref","is-referenced-by-count":257,"title":["Disrupted Dentate Granule Cell Chloride Regulation Enhances Synaptic Excitability during Development of Temporal Lobe Epilepsy"],"prefix":"10.1523","volume":"27","author":[{"given":"Hemal R.","family":"Pathak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Weissinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Terunuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory 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