{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:17:49Z","timestamp":1789179469423,"version":"build-2803163510"},"reference-count":23,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2001,4,1]]},"abstract":"<jats:p>In the absence of vasopressin, medullary thick ascending limb cells express a K<jats:sup>+<\/jats:sup>-independent, furosemide-sensitive Na<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>cotransporter that is inhibited by hypertonicity. The murine renal specific Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2 Cl<jats:sup>\u2212<\/jats:sup>cotransporter gene ( SLC12A1) gives rise to six alternatively spliced isoforms. Three feature a long COOH-terminal domain that encodes the butmetanide-sensitive Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2 Cl<jats:sup>\u2212<\/jats:sup>cotransporter (BSC1\u20139\/NKCC2), and three with a short COOH-terminal domain, known as mBSC1-A4, B4, or F4 (19). Here we have determined the functional characteristics of mBSC1-A4, as expressed in Xenopus laevis oocytes. When incubated at normal oocyte osmolarity (\u223c200 mosmol\/kgH<jats:sub>2<\/jats:sub>O), mBSC1\u20134-injected oocytes do not express significant Na<jats:sup>+<\/jats:sup>uptake over H<jats:sub>2<\/jats:sub>O-injected controls, and immunohistochemical analysis shows that the majority of mBSC1\u20134 protein is in the oocyte cytoplasm and not at the plasma membrane. In contrast, when mBSC1\u20134 oocytes are exposed to hypotonicity (\u223c100 mosmol\/kgH<jats:sub>2<\/jats:sub>O), a significant increase in Na<jats:sup>+<\/jats:sup>uptake but not in<jats:sup>86<\/jats:sup>Rb<jats:sup>+<\/jats:sup>uptake is observed. The increased Na<jats:sup>+<\/jats:sup>uptake is Cl<jats:sup>\u2212<\/jats:sup>dependent, furosemide sensitive, and cAMP sensitive but K<jats:sup>+<\/jats:sup>independent. Sodium uptake increases with decreasing osmolarity between 120 and 70 mosmol\/kgH<jats:sub>2<\/jats:sub>O ( r = 0.95, P &lt; 0.01). Immunohistochemical analysis shows that in hypotonic conditions mBSC1-A4 protein is expressed in the plasma membrane. These studies indicate that the mBSC1-A4 isoform of the SLC12A1 gene encodes a hypotonically activated, cAMP- and furosemide-sensitive Na<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>cotransporter. Thus it is possible that alternative splicing of the BSC1 gene could provide the molecular mechanism enabling the Na<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>-to-Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>switching in thick ascending limb cells.<\/jats:p>","DOI":"10.1152\/ajprenal.2001.280.4.f574","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T13:16:53Z","timestamp":1514035013000},"page":"F574-F582","source":"Crossref","is-referenced-by-count":52,"title":["Alternatively spliced isoform of apical Na<sup>+<\/sup>-K<sup>+<\/sup>-Cl<sup>\u2212<\/sup>cotransporter gene encodes a furosemide-sensitive Na<sup>+<\/sup>-Cl<sup>\u2212<\/sup>cotransporter"],"prefix":"10.1152","volume":"280","author":[{"given":"Consuelo","family":"Plata","sequence":"first","affiliation":[{"name":"Molecular Physiology Unit, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n and Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City CP 14000, Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Meade","sequence":"additional","affiliation":[{"name":"Molecular Physiology Unit, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n and Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City CP 14000, Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University Medical School, New Haven, Connecticut 06520; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick C.","family":"Welch","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Molecular Physiology Unit, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n and Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City CP 14000, Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Hebert","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Yale University Medical School, New Haven, Connecticut 06520; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Gamba","sequence":"additional","affiliation":[{"name":"Molecular Physiology Unit, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n and Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City CP 14000, Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1985.249.1.F34"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00581776"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1051360203"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1986.250.1.F176"},{"key":"B6","doi-asserted-by":"crossref","first-page":"17713","DOI":"10.1016\/S0021-9258(17)32499-7","volume":"296","author":"Gamba G","year":"1994","journal-title":"J Biol Chem"},{"key":"B7","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/S0026-895X(25)13396-8","volume":"33","author":"Garay RP","year":"1988","journal-title":"Mol Pharmacol"},{"key":"B8","first-page":"S211","volume":"3","author":"Giesen-Crouse E","year":"1985","journal-title":"J Hypertens,"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(85)90516-3"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.27.16237"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.260.4.C791"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.275.3.F325"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1984.246.6.F745"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/BF01868440"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1981.241.4.F432"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1981.241.4.F443"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1995.269.3.F405"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.1.F161"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.276.3.F347"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.23.16355"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.276.3.F359"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(90)90412-H"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/BF01868594"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7332"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.2001.280.4.F574","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T04:37:26Z","timestamp":1751171846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.2001.280.4.F574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,4,1]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,4,1]]}},"alternative-id":["10.1152\/ajprenal.2001.280.4.F574"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.2001.280.4.f574","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,4,1]]}}}