{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:36:58Z","timestamp":1792726618182,"version":"4.5.0"},"reference-count":29,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2012,9,1]]},"abstract":"<jats:p>Kidney-specific WNK1 (KS-WNK1) is a variant of full-length WNK1. Previous studies have reported that KS-WNK1 is predominantly expressed in the distal convoluted tubule (DCT) where it regulates sodium-chloride cotransporter. The role of KS-WNK1 in other nephron segments is less clear. Here, we measured the expression of KS-WNK1 transcript in microdissected renal tubules and found that KS-WNK1 was most abundant in the DCT, followed by cortical thick ascending limb (cTAL), connecting tubule, and cortical collecting duct. A high K<jats:sup>+<\/jats:sup>diet enhanced the expression of KS-WNK1 in the DCT and cTAL, selectively. It has been reported that a high-K diet suppresses Na<jats:sup>+<\/jats:sup>reabsorption in TAL. To understand the role of KS-WNK1 in Na<jats:sup>+<\/jats:sup>transport in cTAL and the regulation by dietary K<jats:sup>+<\/jats:sup>, we examined Na<jats:sup>+<\/jats:sup>reabsorption using in vitro microperfusion in cTAL isolated from KS-WNK1-knockout mice and wild-type littermates fed either a control-K<jats:sup>+<\/jats:sup>or high-K<jats:sup>+<\/jats:sup>diet. Furosemide-sensitive Na<jats:sup>+<\/jats:sup>reabsorption in cTAL was higher in KS-WNK1-knockout (KO) mice than in wild-type. A high-K<jats:sup>+<\/jats:sup>diet inhibited Na<jats:sup>+<\/jats:sup>reabsorption in cTAL from wild-type mice, but the inhibition was eliminated in KS-WNK1-KO mice. We further examined the role of KS-WNK1 using transgenic mice that overexpress KS-WNK1. Na<jats:sup>+<\/jats:sup>reabsorption in cTAL was lower in transgenic than in wild-type mice. In whole animal clearance studies, a high-K<jats:sup>+<\/jats:sup>diet increased daily urine volume and urinary Na<jats:sup>+<\/jats:sup>and K<jats:sup>+<\/jats:sup>excretion in wild-type mice, which was blunted in KS-WNK1-KO mice. Thus KS-WNK1 inhibits Na<jats:sup>+<\/jats:sup>reabsorption in cTAL and mediates the inhibition of Na<jats:sup>+<\/jats:sup>reabsorption in the segment by a high-K diet.<\/jats:p>","DOI":"10.1152\/ajprenal.00290.2012","type":"journal-article","created":{"date-parts":[[2012,7,12]],"date-time":"2012-07-12T04:24:03Z","timestamp":1342067043000},"page":"F667-F673","source":"Crossref","is-referenced-by-count":42,"title":["Kidney-specific WNK1 inhibits sodium reabsorption in the cortical thick ascending limb"],"prefix":"10.1152","volume":"303","author":[{"given":"Chih-Jen","family":"Cheng","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;"},{"name":"Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao","family":"Truong","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Baum","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;"},{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chou-Long","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1152\/ajplegacy.1972.222.2.421","volume":"222","author":"Brandis M","year":"1972","journal-title":"Am J Physiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00633.2011"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(97)90079-2"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.24.9208-9221.2003"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2001.7775"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00053.2006"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303435200"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006128107"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30087"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e32830dd580"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00598.2010"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00522.2009"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00366.2007"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510609103"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806551200"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq525"},{"key":"B17","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1242\/jeb.177.1.273","volume":"177","author":"Maddrell SH","year":"1993","journal-title":"J Exp Biol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1993.265.3.F361"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510042200"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005111197"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00122.2003"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.243by.x"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00280.2005"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1994.371"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062844"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.22.16795"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkf492"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17443"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00290.2012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T23:37:35Z","timestamp":1642721855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00290.2012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,1]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,9,1]]}},"alternative-id":["10.1152\/ajprenal.00290.2012"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00290.2012","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,1]]}}}