{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:02:34Z","timestamp":1791266554565,"version":"4.1.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,12,21]]},"abstract":"<jats:p>\n                    Inward-rectifier K\n                    <jats:sup>+<\/jats:sup>\n                    channels of the ROMK (K\n                    <jats:sub>ir<\/jats:sub>\n                    1.1) subtype are responsible for K\n                    <jats:sup>+<\/jats:sup>\n                    secretion and control of NaCl absorption in the kidney. A hallmark of these channels is their gating by intracellular pH in the neutral range. Here we show that a lysine residue close to TM1, identified previously as a structural element required for pH-induced gating, is protonated at neutral pH and that this protonation drives pH gating in ROMK and other K\n                    <jats:sub>ir<\/jats:sub>\n                    channels. Such anomalous titration of this lysine residue (Lys-80 in K\n                    <jats:sub>ir<\/jats:sub>\n                    1.1) is accomplished by the tertiary structure of the K\n                    <jats:sub>ir<\/jats:sub>\n                    protein: two arginines in the distant N and C termini of the same subunit (Arg-41 and Arg-311 in K\n                    <jats:sub>ir<\/jats:sub>\n                    1.1) are located in close spatial proximity to the lysine allowing for electrostatic interactions that shift its pK\n                    <jats:sub>a<\/jats:sub>\n                    into the neutral pH range. Structural disturbance of this triad as a result from a number of point mutations found in patients with antenatal Bartter syndrome shifts the pK\n                    <jats:sub>a<\/jats:sub>\n                    of the lysine residue off the neutral pH range and results in channels permanently inactivated under physiological conditions. Thus, the results provide molecular understanding for normal pH gating of K\n                    <jats:sub>ir<\/jats:sub>\n                    channels as well as for the channel defects found in patients with antenatal Bartter syndrome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.26.15298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:43:20Z","timestamp":1027680200000},"page":"15298-15303","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":130,"title":["pH gating of ROMK (K\n                    <sub>ir<\/sub>\n                    1.1) channels: Control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome"],"prefix":"10.1073","volume":"96","author":[{"given":"U.","family":"Schulte","sequence":"first","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Konrad","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Jeck","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Derst","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Wild","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Weidemann","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Ruppersberg","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Fakler","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Ob dem Himmelreich 7, 72074 T\u00fcbingen, Germany, and Department of Pediatrics and Institut of Physiology, Philipps University, Deutschhausstr. 12, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,12,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.54.030192.000501"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.274.5.F817"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.275.3.F325"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/362031a0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.59.1.171"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-4388(95)80038-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1995.0145"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90021-7"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.31.19699"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/374135a0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90459-X"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7973666"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/372366a0"},{"key":"e_1_3_3_14_2","first-page":"F1132","volume":"268","author":"Boim M A","year":"1995","unstructured":"M A Boim, K Ho, M E Shuck, M J Bienkowski, J H Block, J L Slightom, Y Yang, B M Brenner, S C Hebert Am J Physiol 268, F1132\u2013F1140 (1995).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.266.3.C809"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.268.1.C127"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.29.17261"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00784.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.268.5.C1173"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.51.34575"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1997.273.4.F516"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-183"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-152"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.1.17"},{"key":"e_1_3_3_25_2","volume-title":"Hypokalemic Tubular Disorders: The Hyperprostaglandine E Syndrome and Gitelman-Bartter Syndrome","author":"Seyberth H","year":"1997","unstructured":"H Seyberth, M Soergel, A K\u00f6ckerling Hypokalemic Tubular Disorders: The Hyperprostaglandine E Syndrome and Gitelman-Bartter Syndrome (Oxford Univ. Press, Oxford, 1997)."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050223"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.6024"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.37.23884"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.105.1.61"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00722a043"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1159\/000154823"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020225"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00096a004"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(94)90132-5"},{"key":"e_1_3_3_35_2","volume-title":"Data for Biochemical Research","author":"Dawson R","year":"1986","unstructured":"R Dawson, D Elliot, W Elliot, K Jones Data for Biochemical Research (Oxford Univ. Press, 3rd Ed., London, 1986).","edition":"3"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0698-459"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/35882"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1138"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1141"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.16.9313"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.96.26.15298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:19:32Z","timestamp":1649870372000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.96.26.15298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,12,21]]},"references-count":40,"journal-issue":{"issue":"26","published-print":{"date-parts":[[1999,12,21]]}},"alternative-id":["10.1073\/pnas.96.26.15298"],"URL":"https:\/\/doi.org\/10.1073\/pnas.96.26.15298","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,12,21]]},"assertion":[{"value":"1999-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-12-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}