{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T23:38:18Z","timestamp":1769816298169,"version":"3.49.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2000,12,1]]},"abstract":"<jats:p> In this study, we examined the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup> cotransporter activity and expression in rat cortical astrocyte differentiation. Astrocyte differentiation was induced by dibutyryl cAMP (DBcAMP, 0.25 mM) for 7 days, and cells changed from a polygonal to process-bearing morphology. Basal activity of the cotransporter was significantly increased in DBcAMP-treated astrocytes ( P &lt; 0.05). Expression of an \u223c161-kDa cotransporter protein was increased by 91% in the DBcAMP-treated astrocytes. Moreover, the specific [<jats:sup>3<\/jats:sup>H]bumetanide binding was increased by 67% in the DBcAMP-treated astrocytes. Inhibition of protein synthesis by cyclohexamide (2\u20133 \u03bcg\/ml) significantly attenuated the DBcAMP-mediated upregulation of the cotransporter activity and expression. The Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>cotransporter in astrocytes has been suggested to play a role in K<jats:sup>+<\/jats:sup> uptake. In 75 mM extracellular K<jats:sup>+<\/jats:sup>concentration, the cotransporter-mediated K<jats:sup>+<\/jats:sup> influx was stimulated by 147% in nontreated cells and 79% in DBcAMP-treated cells ( P &lt; 0.05). To study whether this high K<jats:sup>+<\/jats:sup>-induced stimulation of the cotransporter is attributed to membrane depolarization and Ca<jats:sup>2+<\/jats:sup> influx, the role of the L-type voltage-dependent Ca<jats:sup>2+<\/jats:sup> channel was investigated. The high-K<jats:sup>+<\/jats:sup>-mediated stimulation of the cotransporter activity was abolished in the presence of either 0.5 or 1.0 \u03bcM of the L-type channel blocker nifedipine or Ca<jats:sup>2+<\/jats:sup>-free HEPES buffer. A rise in intracellular free Ca<jats:sup>2+<\/jats:sup> in astrocytes was observed in high K<jats:sup>+<\/jats:sup>. These results provide the first evidence that the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup> cotransporter protein expression can be regulated selectively when intracellular cAMP is elevated. The study also demonstrates that the cotransporter in astrocytes is stimulated by high K<jats:sup>+<\/jats:sup> in a Ca<jats:sup>2+<\/jats:sup>-dependent manner. <\/jats:p>","DOI":"10.1152\/ajpcell.2000.279.6.c1710","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T23:05:08Z","timestamp":1514156708000},"page":"C1710-C1721","source":"Crossref","is-referenced-by-count":60,"title":["Regulation of Na<sup>+<\/sup>-K<sup>+<\/sup>-Cl<sup>\u2212<\/sup>cotransporter in primary astrocytes by dibutyryl cAMP and high [K<sup>+<\/sup>]<sub>o<\/sub>"],"prefix":"10.1152","volume":"279","author":[{"given":"Gui","family":"Su","sequence":"first","affiliation":[{"name":"Departments of Neurological Surgery,"},{"name":"Physiology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Haworth","sequence":"additional","affiliation":[{"name":"Surgery, School of Medicine, University of Wisconsin, Madison, Wisconsin 53792"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Dempsey","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Sun","sequence":"additional","affiliation":[{"name":"Departments of Neurological Surgery,"},{"name":"Physiology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.110.4.453"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1988.tb13807.x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.46.28969"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90059-0"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)44299-2"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.51.030189.002303"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.267.4.C869"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83931-5"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020521308985"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.264.1.C189"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(98)90050-1"},{"key":"B14","first-page":"603","volume":"8","author":"Hertz L","year":"1985","journal-title":"Cell cultures. 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