{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:16:21Z","timestamp":1791148581406,"version":"4.1.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2002,5,1]]},"abstract":"<jats:p> We hypothesized that high extracellular K<jats:sup>+<\/jats:sup> concentration ([K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>)-mediated stimulation of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup> cotransporter isoform 1 (NKCC1) may result in a net gain of K<jats:sup>+<\/jats:sup> and Cl<jats:sup>\u2212<\/jats:sup>and thus lead to high-[K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>-induced swelling and glutamate release. In the current study, relative cell volume changes were determined in astrocytes. Under 75 mM [K<jats:sup>+<\/jats:sup>]<jats:sub>o,<\/jats:sub> astrocytes swelled by 20.2 \u00b1 4.9%. This high-[K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>-mediated swelling was abolished by the NKCC1 inhibitor bumetanide (10 \u03bcM, 1.0 \u00b1 3.1%; P &lt; 0.05). Intracellular<jats:sup>36<\/jats:sup>Cl<jats:sup>\u2212<\/jats:sup> accumulation was increased from a control value of 0.39 \u00b1 0.06 to 0.68 \u00b1 0.05 \u03bcmol\/mg protein in response to 75 mM [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>. This increase was significantly reduced by bumetanide ( P &lt; 0.05). Basal intracellular Na<jats:sup>+<\/jats:sup> concentration ([Na<jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>) was reduced from 19.1 \u00b1 0.8 to 16.8 \u00b1 1.9 mM by bumetanide ( P &lt; 0.05). [Na<jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub> decreased to 8.4 \u00b1 1.0 mM under 75 mM [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> and was further reduced to 5.2 \u00b1 1.7 mM by bumetanide. In addition, the recovery rate of [Na<jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub> on return to 5.8 mM [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> was decreased by 40% in the presence of bumetanide ( P &lt; 0.05). Bumetanide inhibited high-[K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>-induced <jats:sup>14<\/jats:sup>C-labeledd-aspartate release by \u223c50% ( P &lt; 0.05). These results suggest that NKCC1 contributes to high-[K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>-induced astrocyte swelling and glutamate release. <\/jats:p>","DOI":"10.1152\/ajpcell.00478.2001","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T00:08:22Z","timestamp":1368490102000},"page":"C1136-C1146","source":"Crossref","is-referenced-by-count":134,"title":["Contribution of Na<sup>+<\/sup>-K<sup>+<\/sup>-Cl<sup>\u2212<\/sup>cotransporter to high-[K<sup>+<\/sup>]<sub>o<\/sub>-  induced swelling and EAA release in astrocytes"],"prefix":"10.1152","volume":"282","author":[{"given":"Gui","family":"Su","sequence":"first","affiliation":[{"name":"Departments of Neurological Surgery and"},{"name":"Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B.","family":"Kintner","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Sun","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery and"},{"name":"Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1136(200010)32:1<1::AID-GLIA10>3.0.CO;2-W"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-02-00666.2000"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90145-H"},{"key":"B5","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1113\/jphysiol.1993.sp019735","volume":"466","author":"Barbour B","year":"1993","journal-title":"J Physiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-12-04637.1998"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.110.3.297"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(90)90013-7"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-04-02720.1995"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.085aa.x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-5876-4_22"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5233.99"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1999.81.1.49"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.83.1.406"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.1.31"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-05-01800.2000"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1139\/y87-163"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1995.51"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00152-9"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-20-07817.1997"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.273.5.C1516"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.1.626"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021216"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-10-03554.1998"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.1.211"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.274.6.C1511"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-24-07803.1996"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1992.77.2.0169"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(85)90442-7"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00189-1"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.111.5.617"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.6.C1710"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00538.2001"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-20-07531.2000"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-03-00932.1997"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1139\/y92-270"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(88)90123-9"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1139\/y92-271"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.275.6.C1565"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02649-X"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200106000-00009"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00478.2001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:10:10Z","timestamp":1718651410000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00478.2001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,1]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2002,5,1]]}},"alternative-id":["10.1152\/ajpcell.00478.2001"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00478.2001","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,5,1]]}}}