{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:19:02Z","timestamp":1792685942084,"version":"4.5.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,1]]},"abstract":"\n We recently described a novel thiazide\u2013sensitive electroneutral NaCl transport mechanism resulting from the parallel operation of the Cl\n \u2212<\/jats:sup>\n \/HCO\n 3<\/jats:sub>\n \u2212<\/jats:sup>\n exchanger pendrin and the Na\n +<\/jats:sup>\n \u2013driven Cl\n \u2212<\/jats:sup>\n \/2HCO\n 3<\/jats:sub>\n \u2212<\/jats:sup>\n exchanger (NDCBE) in\n \u03b2<\/jats:italic>\n -intercalated cells of the collecting duct. Although a role for pendrin in maintaining Na\n +<\/jats:sup>\n balance, intravascular volume, and BP is well supported, there is no\n in vivo<\/jats:italic>\n evidence for the role of NDCBE in maintaining Na\n +<\/jats:sup>\n balance. Here, we show that deletion of NDCBE in mice caused only subtle perturbations of Na\n +<\/jats:sup>\n homeostasis and provide evidence that the Na\n +<\/jats:sup>\n \/Cl\n \u2212<\/jats:sup>\n cotransporter (NCC) compensated for the inactivation of NDCBE. To unmask the role of NDCBE, we generated\n Ndcbe\/Ncc<\/jats:italic>\n double\u2013knockout (dKO) mice. On a normal salt diet, dKO and single-knockout mice exhibited similar activation of the renin-angiotensin-aldosterone system, whereas only dKO mice displayed a lower blood K\n +<\/jats:sup>\n concentration. Furthermore, dKO mice displayed upregulation of the epithelial sodium channel (ENaC) and the Ca\n 2+<\/jats:sup>\n \u2013activated K\n +<\/jats:sup>\n channel BKCa. During NaCl depletion, only dKO mice developed marked intravascular volume contraction, despite dramatically increased renin activity. Notably, the increase in aldosterone levels expected on NaCl depletion was attenuated in dKO mice, and single-knockout and dKO mice had similar blood K\n +<\/jats:sup>\n concentrations under this condition. In conclusion, NDCBE is necessary for maintaining sodium balance and intravascular volume during salt depletion or NCC inactivation in mice. Furthermore, NDCBE has an important role in the prevention of hypokalemia. Because NCC and NDCBE are both thiazide targets, the combined inhibition of NCC and the NDCBE\/pendrin system may explain thiazide-induced hypokalemia in some patients.\n <\/jats:p>","DOI":"10.1681\/asn.2015070734","type":"journal-article","created":{"date-parts":[[2016,5,6]],"date-time":"2016-05-06T00:48:50Z","timestamp":1462495730000},"page":"130-139","source":"Crossref","is-referenced-by-count":52,"title":["Double Knockout of the Na+-Driven Cl\u2212\/HCO3 \u2212 Exchanger and Na+\/Cl\u2212 Cotransporter Induces Hypokalemia and Volume Depletion"],"prefix":"10.1681","volume":"28","author":[{"given":"Anne","family":"Sinning","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Humangenetik, University Hospital Jena, Friedrich Schiller Universit\u00e4t, Jena, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Radionov","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U970, Paris Cardiovascular Research Center, Paris, France;"},{"name":"Faculty de Medicine, Universit\u00e9 Paris-Descartes, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Trepiccione","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U970, Paris Cardiovascular Research Center, Paris, France;"},{"name":"Faculty de Medicine, Universit\u00e9 Paris-Descartes, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen I.","family":"L\u00f3pez-Cayuqueo","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U970, Paris Cardiovascular Research Center, Paris, France;"},{"name":"Faculty de Medicine, Universit\u00e9 Paris-Descartes, Paris, France;"},{"name":"Centro de Estudios Cient\u00edficos (CECs), Valdivia, Chile;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilien","family":"Jayat","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U970, Paris Cardiovascular Research Center, Paris, France;"},{"name":"Faculty de Medicine, Universit\u00e9 Paris-Descartes, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Baron","sequence":"additional","affiliation":[{"name":"Department de Physiologie, Hopital Europ\u00e9en Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Corni\u00e8re","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie et Transplantation R\u00e9nale, Centre Hospitalier Universitaire de La R\u00e9union, St. Denis, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Todd","family":"Alexander","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Physiology, University of Alberta, Edmonton, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Hadchouel","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U970, Paris Cardiovascular Research Center, Paris, France;"},{"name":"Faculty de Medicine, Universit\u00e9 Paris-Descartes, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Eladari","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U970, Paris Cardiovascular Research Center, Paris, France;"},{"name":"Faculty de Medicine, Universit\u00e9 Paris-Descartes, Paris, France;"},{"name":"Department de Physiologie, Hopital Europ\u00e9en Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A.","family":"H\u00fcbner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, University Hospital Jena, Friedrich Schiller Universit\u00e4t, Jena, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9gine","family":"Chambrey","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U970, Paris Cardiovascular Research Center, Paris, France;"},{"name":"Faculty de Medicine, Universit\u00e9 Paris-Descartes, Paris, France;"},{"name":"Centre National de la Recherche Scientifique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,5,5]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1126\/science.2063193","article-title":"Blood pressure control--special role of the kidneys and 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in the renal cortical collecting ducts of mice.","volume":"120","author":"Leviel","year":"2010","journal-title":"J Clin Invest"},{"key":"B5-20230819","doi-asserted-by":"crossref","first-page":"7928","DOI":"10.1073\/pnas.1221496110","article-title":"Renal intercalated cells are rather energized by a proton than a sodium pump.","volume":"110","author":"Chambrey","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B6-20230819","doi-asserted-by":"crossref","first-page":"F1314","DOI":"10.1152\/ajprenal.00155.2007","article-title":"Reduced ENaC protein abundance contributes to the lower blood pressure observed in pendrin-null mice.","volume":"293","author":"Kim","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"key":"B7-20230819","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1161\/01.HYP.0000088321.67254.B7","article-title":"Deoxycorticosterone upregulates PDS (Slc26a4) in mouse kidney: Role of pendrin in mineralocorticoid-induced hypertension.","volume":"42","author":"Verlander","year":"2003","journal-title":"Hypertension"},{"key":"B8-20230819","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1681\/ASN.2012080787","article-title":"Overexpression of pendrin in intercalated cells produces chloride-sensitive hypertension.","volume":"24","author":"Jacques","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B9-20230819","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1681\/ASN.2005101054","article-title":"Pendrin regulation in mouse kidney primarily is chloride-dependent.","volume":"17","author":"Vallet","year":"2006","journal-title":"J Am Soc Nephrol"},{"key":"B10-20230819","doi-asserted-by":"crossref","first-page":"20447","DOI":"10.1074\/jbc.R800083200","article-title":"ENaC at the cutting edge: Regulation of epithelial sodium channels by proteases.","volume":"284","author":"Kleyman","year":"2009","journal-title":"J Biol 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Physiol"},{"key":"B14-20230819","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1161\/01.HYP.0000145863.96091.89","article-title":"NaCl restriction upregulates renal Slc26a4 through subcellular redistribution: Role in Cl- conservation.","volume":"44","author":"Wall","year":"2004","journal-title":"Hypertension"},{"key":"B15-20230819","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1097\/01.ASN.0000138234.18569.63","article-title":"Altered renal distal tubule structure and renal Na(+) and Ca(2+) handling in a mouse model for Gitelman\u2019s syndrome.","volume":"15","author":"Loffing","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"B16-20230819","doi-asserted-by":"crossref","first-page":"29150","DOI":"10.1074\/jbc.273.44.29150","article-title":"Phenotype resembling Gitelman\u2019s syndrome in mice lacking the apical Na+-Cl- cotransporter of the distal convoluted tubule.","volume":"273","author":"Schultheis","year":"1998","journal-title":"J Biol 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