{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:42:57Z","timestamp":1778276577642,"version":"3.51.4"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T00:00:00Z","timestamp":1033430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:p>The ROMK subtypes of inward\u2010rectifier K<jats:sup>+<\/jats:sup> channels mediate potassium secretion and regulate <jats:styled-content>NaCl<\/jats:styled-content> reabsorption in the kidney. Loss\u2010of\u2010function mutations in this pH\u2010sensitive K<jats:sup>+<\/jats:sup> channel cause Bartter's disease, a familial salt wasting nephropathy. One disease\u2010causing mutation truncates the extreme COOH\u2010terminus and induces a closed gating conformation. Here we identify a region within the deleted domain that plays an important role in pH\u2010dependent gating. The domain contains a structural element that functionally interacts with the pH sensor in the cytoplasmic NH<jats:sub>2<\/jats:sub><jats:bold>\u2010<\/jats:bold>terminus to set a physiological range of pH sensitivity. Removal of the domain shifts the p<jats:italic>K<\/jats:italic><jats:sub>a<\/jats:sub> towards alkaline pH values, causing channel inactivation under physiological conditions. Suppressor mutations within the pH sensor rescued channel gating and trans addition of the cognate peptide restored pH sensitivity. A specific interdomain interaction was revealed in an <jats:italic>in vitro<\/jats:italic> protein\u2010protein binding assay between the NH<jats:sub>2<\/jats:sub>\u2010 and COOH\u2010terminal cytoplasmic domains expressed as bacterial fusion proteins. These results provide new insights into the molecular mechanisms underlying Kir channel regulation and channel gating defects that are associated with Bartter's disease.<\/jats:p>","DOI":"10.1113\/jphysiol.2002.027581","type":"journal-article","created":{"date-parts":[[2002,10,15]],"date-time":"2002-10-15T16:45:17Z","timestamp":1034700317000},"page":"351-362","source":"Crossref","is-referenced-by-count":26,"title":["Molecular mechanism of a COOH\u2010terminal gating determinant in the ROMK channel revealed by a Bartter's disease mutation"],"prefix":"10.1113","volume":"544","author":[{"given":"Thomas P.","family":"Flagg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher 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