{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:41:57Z","timestamp":1791160917892,"version":"4.1.0"},"reference-count":41,"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 reported previously that inhibition of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup> cotransporter isoform 1 (NKCC1) by bumetanide abolishes high extracellular K<jats:sup>+<\/jats:sup>concentration ([K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>)-induced swelling and intracellular Cl<jats:sup>\u2212<\/jats:sup> accumulation in rat cortical astrocytes. In this report, we extended our study by using cortical astrocytes from NKCC1-deficient (NKCC1<jats:sup>\u2212\/\u2212<\/jats:sup>) mice. NKCC1 protein and activity were absent in NKCC1<jats:sup>\u2212\/\u2212<\/jats:sup> astrocytes. [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> of 75 mM increased NKCC1 activity approximately fourfold in NKCC1<jats:sup>+\/+<\/jats:sup> cells ( P&lt; 0.05) but had no effect in NKCC1<jats:sup>\u2212\/\u2212<\/jats:sup> astrocytes. Intracellular Cl<jats:sup>\u2212<\/jats:sup> was increased by 70% in NKCC1<jats:sup>+\/+<\/jats:sup> astrocytes under 75 mM [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> ( P &lt; 0.05) but remained unchanged in NKCC1<jats:sup>\u2212\/\u2212<\/jats:sup> astrocytes. Baseline intracellular Na<jats:sup>+<\/jats:sup> concentration ([Na<jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>) in NKCC1<jats:sup>+\/+<\/jats:sup> astrocytes was 19.0 \u00b1 0.5 mM, compared with 16.9 \u00b1 0.3 mM [Na<jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub> in NKCC1<jats:sup>\u2212\/\u2212<\/jats:sup> astrocytes ( P &lt; 0.05). Relative cell volume of NKCC1<jats:sup>+\/+<\/jats:sup> astrocytes increased by 13 \u00b1 2% in 75 mM [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>, compared with a value of 1.0 \u00b1 0.5% in NKCC1<jats:sup>\u2212\/\u2212<\/jats:sup> astrocytes ( P &lt; 0.05). Regulatory volume increase after hypertonic shrinkage was completely impaired in NKCC1<jats:sup>\u2212\/\u2212<\/jats:sup> astrocytes. High-[K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>-induced <jats:sup>14<\/jats:sup>C-labeledd-aspartate release was reduced by \u223c30% in NKCC1<jats:sup>\u2212\/\u2212<\/jats:sup> astrocytes. Our study suggests that stimulation of NKCC1 is required for high-[K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>-induced swelling, which contributes to glutamate release from astrocytes under high [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>. <\/jats:p>","DOI":"10.1152\/ajpcell.00538.2001","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T00:08:22Z","timestamp":1368490102000},"page":"C1147-C1160","source":"Crossref","is-referenced-by-count":160,"title":["Astrocytes from Na<sup>+<\/sup>-K<sup>+<\/sup>-Cl<sup>\u2212<\/sup>cotransporter-null mice  exhibit absence of swelling and decrease in EAA release"],"prefix":"10.1152","volume":"282","author":[{"given":"Gui","family":"Su","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery and"},{"name":"Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53792; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B.","family":"Kintner","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Flagella","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E.","family":"Shull","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Sun","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"},{"name":"Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53792; 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