{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:10:50Z","timestamp":1780103450909,"version":"3.54.0"},"reference-count":33,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["A1-S-8290"],"award-info":[{"award-number":["A1-S-8290"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"HHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["DK51496"],"award-info":[{"award-number":["DK51496"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:p> The thiazide-sensitive Na<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup> cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule, and the inhibition of its function with thiazides is widely used for the treatment of arterial hypertension. In mammals and teleosts, NCC is present as one ortholog that is mainly expressed in the kidney. One exception, however, is the eel, which has two genes encoding NCC. The eNCC\u03b1 is located in the kidney and eNCC\u03b2, which is present in the apical membrane of the rectum. Interestingly, the European eNCC\u03b2 functions as a Na<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup> cotransporter that is nevertheless resistant to thiazides and is not activated by low-chloride hypotonic stress. However, in the Japanese eel rectal sac, a thiazide-sensitive NaCl transport mechanism has been described. The protein sequences between eNCC\u03b2 and jNCC\u03b2 are 98% identical. Here, by site-directed mutagenesis, we transformed eNCC\u03b2 into jNCC\u03b2. Our data showed that jNCC\u03b2, similar to eNCC\u03b2, is resistant to thiazides. In addition, both NCC\u03b2 proteins have high transport capacity with respect to their renal NCC orthologs and, in contrast to known NCCs, exhibit electrogenic properties that are reduced when residue I172 is substituted by A, G, or M. This is considered a key residue for the chloride ion-binding sites of NKCC and KCC. We conclude that NCC\u03b2 proteins are not sensitive to thiazides and have electrogenic properties dependent on Cl<jats:sup>\u2212<\/jats:sup>, and site I172 is important for the function of NCC\u03b2. <\/jats:p>","DOI":"10.1152\/ajpcell.00213.2022","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T17:19:34Z","timestamp":1656350374000},"page":"C385-C399","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["The European and Japanese eel NaCl cotransporters \u03b2 exhibit chloride currents and are resistant to thiazide type diuretics"],"prefix":"10.1152","volume":"323","author":[{"given":"Erika","family":"Moreno","sequence":"first","affiliation":[{"name":"Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Plata","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"},{"name":"Molecular Physiology Unit, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dulce Mar\u00eda","family":"Oropeza-Viveros","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Pacheco-Alvarez","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Rojas-Vega","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viridiana","family":"Olin-Sandoval","sequence":"additional","affiliation":[{"name":"Department of Physiology of Nutrition, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4378-9043","authenticated-orcid":true,"given":"Gerardo","family":"Gamba","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"},{"name":"Molecular Physiology Unit, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00159.2009"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.37.6.1458"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1969.tb13015.x"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062844"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2218"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nature10814"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.1.F161"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00284.2001"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602614200"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400602200"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00412.2010"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.742783"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3129"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167056"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-01750-w"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100793"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1438-2"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpb.2007.08.007"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2011.04.009"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00071.2005"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609313200"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-009-9165-5"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00574.2013"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00044.2004"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00465.2019"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52505"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00145.2018"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411961200"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00488.2019"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2004"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.11.002"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.063859"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00437-x"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00213.2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T15:13:52Z","timestamp":1718637232000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00213.2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,1]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,8,1]]}},"alternative-id":["10.1152\/ajpcell.00213.2022"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00213.2022","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,1]]},"assertion":[{"value":"2022-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-14","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}