{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:26:22Z","timestamp":1791048382732,"version":"4.1.0"},"reference-count":29,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1999,4,1]]},"abstract":"<jats:p>Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter in immature cortical neurons: a role in intracellular Cl<jats:sup>\u2212<\/jats:sup>regulation. Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter has been suggested to contribute to active intracellular Cl<jats:sup>\u2212<\/jats:sup>accumulation in neurons at both early developmental and adult stages. In this report, we extensively characterized the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter in primary culture of cortical neurons that were dissected from cerebral cortex of rat fetus at embryonic day 17. The Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter was expressed abundantly in soma and dendritic processes of cortical neurons evaluated by immunocytochemical staining. Western blot analysis revealed that an \u223c145-kDa cotransporter protein was present in cerebral cortex at the early postnatal (P0\u2013P9) and adult stages. There was a time-dependent upregulation of the cotransporter activity in cortical neurons during the early postnatal development. A substantial level of bumetanide-sensitive K<jats:sup>+<\/jats:sup>influx was detected in neurons cultured for 4\u20138 days in vitro (DIV 4\u20138). The cotransporter activity was increased significantly at DIV 12 and maintained at a steady level throughout DIV 12\u201314. Bumetanide-sensitive K<jats:sup>+<\/jats:sup>influx was abolished completely in the absence of either extracellular Na<jats:sup>+<\/jats:sup>or Cl<jats:sup>\u2212<\/jats:sup>. Opening of \u03b3-aminobutyric acid (GABA)-activated Cl<jats:sup>\u2212<\/jats:sup>channel or depletion of intracellular Cl<jats:sup>\u2212<\/jats:sup>significantly stimulated the cotransporter activity. Moreover, the cotransporter activity was elevated significantly by activation of N-methyl-d-aspartate ionotropic glutamate receptor via a Ca<jats:sup>2+<\/jats:sup>-dependent mechanism. These results imply that the inwardly directed Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter is important in active accumulation of intracellular Cl<jats:sup>\u2212<\/jats:sup>and may be responsible for GABA-mediated excitatory effect in immature cortical neurons.<\/jats:p>","DOI":"10.1152\/jn.1999.81.4.1939","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T05:15:19Z","timestamp":1514178919000},"page":"1939-1948","source":"Crossref","is-referenced-by-count":96,"title":["Na<sup>+<\/sup>-K<sup>+<\/sup>-2Cl<sup>\u2212<\/sup>Cotransporter in Immature Cortical Neurons: A Role in Intracellular Cl<sup>\u2212<\/sup>Regulation"],"prefix":"10.1152","volume":"81","author":[{"given":"Dandan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery and"},{"name":"Department of Physiology, School of Medicine, University of Wisconsin, Madison, Wisconsin 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangita G.","family":"Murali","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.4.C878"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017378"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015758"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(91)90003-D"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.13.030190.001131"},{"key":"B6","doi-asserted-by":"crossref","first-page":"25677","DOI":"10.1016\/S0021-9258(18)47302-4","volume":"269","author":"Delpire E.","year":"1994","journal-title":"J. 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