{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:32:46Z","timestamp":1791203566341,"version":"4.2.0"},"reference-count":56,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:p> As excitable cells, neurons experience constant changes in their membrane potential due to ion flux through plasma membrane channels. They maintain their transmembrane cation concentrations through robust Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase pump activity. During synaptic transmission and spread of action potentials, the concentration of the major anion, Cl<jats:sup>\u2212<\/jats:sup>, is also under constant challenge from membrane potential changes. Moreover, intracellular Cl<jats:sup>\u2212<\/jats:sup> is also affected by ligand-gated Cl<jats:sup>\u2212<\/jats:sup> channels such as GABA<jats:sub>A<\/jats:sub> and glycine receptors. To regulate intracellular Cl<jats:sup>\u2212<\/jats:sup> in an electrically silent manner, neurons couple the movement of Cl<jats:sup>\u2212<\/jats:sup> with K<jats:sup>+<\/jats:sup>. In this study, we have used gene-targeted KCC2<jats:sup>\u2212\/\u2212<\/jats:sup> mice to provide strong evidence that KCC2, the neuronal-specific K-Cl co-transporter, drives neuronal Cl<jats:sup>\u2212<\/jats:sup> to low concentrations, shifting the GABA reversal potential toward more negative potentials, thus promoting hyperpolarizing GABA responses. Cortical neurons lacking KCC2, not only fail to show a developmental decrease in [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>, but also are unable to regulate [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> on Cl<jats:sup>\u2212<\/jats:sup> loading or maintain [Cl]<jats:sub>i<\/jats:sub> during membrane depolarization. These data are consistent with the central role of KCC2 in promoting inhibition and preventing hyperexcitability. <\/jats:p>","DOI":"10.1152\/jn.00616.2004","type":"journal-article","created":{"date-parts":[[2004,10,6]],"date-time":"2004-10-06T20:13:34Z","timestamp":1097093614000},"page":"1557-1568","source":"Crossref","is-referenced-by-count":140,"title":["Cortical Neurons Lacking KCC2 Expression Show Impaired Regulation of Intracellular Chloride"],"prefix":"10.1152","volume":"93","author":[{"given":"Lei","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lovinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Delpire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017378"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-10-04134.2003"},{"key":"R3","unstructured":"Baughman RW, Huettner JE, Jones KA, and Khan AA. Cell culture of neocortex and basal forebrain from postnatal rats. In: Culturing Nerve Cells, edited by Banker G and Goslin K. Cambridge, MA: MIT Press, 1991, p. 227\u2013249."},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017762"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)60545-2"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(98)00078-9"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/nature01868"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-21-08069.2000"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1038\/9713"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00121.x"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.79.1.439"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00341-5"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01600.x"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00297-5"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.06-10-03044.1986"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(88)90180-0"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.84.1.281"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-10-06890.1995"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Karadsheh MF, Byun N, Mount DB, and Delpire E. Localization of the KCC4 potassium-chloride co-transporter in the nervous system. Neuroscience 123: 381\u2013391, 2003.","DOI":"10.1016\/j.neuroscience.2003.10.004"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.2.995"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02419.x"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90008-X"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(19990615)39:4<558::AID-NEU9>3.0.CO;2-5"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2003.03069.x"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1991.65.2.247"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003112200"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-05-01636.1999"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1126\/science.2424084"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.23.16355"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(83)90076-9"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(89)90063-1"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-20-06414.1996"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.273.5.C1516"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.27.16245"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00567-4"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.272.1.C173"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(19971120)33:6<781::AID-NEU6>3.0.CO;2-5"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200209011"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1038\/16697"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-01-00082.1996"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1126\/science.7871435"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00229.2002"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00190-0"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.72.1.273"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80186-5"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638623"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10983"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.3.C860"},{"key":"R48A","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-20-07531.2000"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(88)90479-X"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.041863"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00172.2003"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-04-01414.2000"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.10014"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-10-03935.1992"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-03-01131.1996"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.00616.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:42:10Z","timestamp":1567989730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.00616.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,3]]}},"alternative-id":["10.1152\/jn.00616.2004"],"URL":"https:\/\/doi.org\/10.1152\/jn.00616.2004","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3]]}}}