{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T10:46:31Z","timestamp":1793357191146,"version":"4.5.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,6,21]]},"abstract":"<jats:p>\n                    The heteromeric inwardly rectifying Kir4.1\/Kir5.1 K\n                    <jats:sup>+<\/jats:sup>\n                    channel underlies the basolateral K\n                    <jats:sup>+<\/jats:sup>\n                    conductance in the distal nephron and is extremely sensitive to inhibition by intracellular pH. The functional importance of Kir4.1\/Kir5.1 in renal ion transport has recently been highlighted by mutations in the human Kir4.1 gene (\n                    <jats:italic>KCNJ10<\/jats:italic>\n                    ) that result in seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME)\/epilepsy, ataxia, sensorineural deafness, and renal tubulopathy (EAST) syndrome, a complex disorder that includes salt wasting and hypokalemic alkalosis. Here, we investigated the role of the Kir5.1 subunit in mice with a targeted disruption of the Kir5.1 gene (\n                    <jats:italic>Kcnj16<\/jats:italic>\n                    ). The\n                    <jats:italic>\n                      Kir5.1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice displayed hypokalemic, hyperchloremic metabolic acidosis with hypercalciuria. The short-term responses to hydrochlorothiazide, an inhibitor of ion transport in the distal convoluted tubule (DCT), were also exaggerated, indicating excessive renal Na\n                    <jats:sup>+<\/jats:sup>\n                    absorption in this segment. Furthermore, chronic treatment with hydrochlorothiazide normalized urinary excretion of Na\n                    <jats:sup>+<\/jats:sup>\n                    and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , and abolished acidosis in\n                    <jats:italic>\n                      Kir5.1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Finally, in contrast to WT mice, electrophysiological recording of K\n                    <jats:sup>+<\/jats:sup>\n                    channels in the DCT basolateral membrane of\n                    <jats:italic>\n                      Kir5.1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice revealed that, even though Kir5.1 is absent, there is an increased K\n                    <jats:sup>+<\/jats:sup>\n                    conductance caused by the decreased pH sensitivity of the remaining homomeric Kir4.1 channels. In conclusion, disruption of\n                    <jats:italic>Kcnj16<\/jats:italic>\n                    induces a severe renal phenotype that, apart from hypokalemia, is the opposite of the phenotype seen in SeSAME\/EAST syndrome. These results highlight the important role that Kir5.1 plays as a pH-sensitive regulator of salt transport in the DCT, and the implication of these results for the correct genetic diagnosis of renal tubulopathies is discussed.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1101400108","type":"journal-article","created":{"date-parts":[[2011,6,2]],"date-time":"2011-06-02T23:04:27Z","timestamp":1307055867000},"page":"10361-10366","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":110,"title":["Renal phenotype in mice lacking the Kir5.1 (\n                    <i>Kcnj16<\/i>\n                    ) K\n                    <sup>+<\/sup>\n                    channel subunit contrasts with that observed in SeSAME\/EAST syndrome"],"prefix":"10.1073","volume":"108","author":[{"given":"Marc","family":"Paulais","sequence":"first","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Bloch-Faure","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Picard","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Jacques","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"},{"name":"Faculty of Medicine, Universit\u00e9 Paris\u2013Descartes, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh Krishna","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Keck","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Sohet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Eladari","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"},{"name":"Faculty of Medicine, Universit\u00e9 Paris\u2013Descartes, 75006 Paris, France;"},{"name":"Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, 75015 Paris, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Houillier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"},{"name":"Faculty of Medicine, Universit\u00e9 Paris\u2013Descartes, 75006 Paris, France;"},{"name":"Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, 75015 Paris, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Lourdel","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Teulon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie Paris 6, Universit\u00e9 Paris 5, and Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, 75006 Paris, France;"},{"name":"Centre National de la Recherche Scientifique, \u00c9quipes de Recherche Labellis\u00e9es 7226, Genomics Physiology, and Renal Physiopathology Laboratory, Centre de Recherche des Cordeliers, 75270 Paris 6, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Clarendon Laboratory and Department of Physics, University of Oxford, Oxford OX1 3PU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.59.1.413"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205627200"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400081101"},{"key":"e_1_3_3_4_2","first-page":"F262","article-title":"Basolateral membrane potassium channels in rabbit cortical thick ascending limb","volume":"263","author":"Hurst AM","year":"1992","unstructured":"AM Hurst, M Duplain, JY Lapointe, Basolateral membrane potassium channels in rabbit cortical thick ascending limb. 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