{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:08:28Z","timestamp":1789967308778,"version":"4.0.1"},"reference-count":68,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,4,24]]},"abstract":"<jats:p>\n                    The cystic fibrosis transmembrane conductance regulator (CFTR)\n protein has the ability to function as both a chloride channel and a\n channel regulator. The loss of these functions explains many of the\n manifestations of the cystic fibrosis disease (CF), including lung and\n pancreatic failure, meconium ileus, and male infertility. CFTR has\n previously been implicated in the cell regulatory volume decrease (RVD)\n response after hypotonic shocks in murine small intestine crypts, an\n effect associated to the dysfunction of an unknown swelling-activated\n potassium conductance. In the present study, we investigated the RVD\n response in human tracheal CF epithelium and the nature of the\n volume-sensitive potassium channel affected. Neither the human tracheal\n cell line CFT1, expressing the mutant CFTR-\u0394F508 gene, nor the\n isogenic vector control line CFT1-LC3, engineered to express the \u03b2gal\n gene, showed RVD. On the other hand, the cell line CFT1-LCFSN,\n engineered to express the wild-type CFTR gene, presented a full RVD.\n Patch-clamp studies of swelling-activated potassium currents in the\n three cell lines revealed that all of them possess a potassium current\n with the biophysical and pharmacological fingerprints of the\n intermediate conductance Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent potassium channel\n (IK, also known as KCNN4). However, only CFT1-LCFSN cells showed an\n increase in IK currents in response to hypotonic challenges. Although\n the identification of the molecular mechanism relating CFTR to the hIK\n channel remains to be solved, these data offer new evidence on the\n complex integration of CFTR in the cells where it is expressed.\n                  <\/jats:p>","DOI":"10.1073\/pnas.091096498","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"5329-5334","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Defective regulatory volume decrease in human cystic fibrosis tracheal cells because of altered regulation of intermediate conductance Ca\n                    <sup>2+<\/sup>\n                    -dependent potassium channels"],"prefix":"10.1073","volume":"98","author":[{"given":"Esther","family":"V\u00e1zquez","sequence":"first","affiliation":[{"name":"Unitat de Senyalitzaci\u00f3 Cel\u00b7lular, Departament de\r Ci\u00e8ncies Experimentals i de la Salut, Universitat Pompeu Fabra,\r C\/Dr. Aiguader 80, 08003 Barcelona, Spain; and Medical\r Research Council Clinical Sciences Centre, Du Cane Road, London W12\r 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Nobles","sequence":"additional","affiliation":[{"name":"Unitat de Senyalitzaci\u00f3 Cel\u00b7lular, Departament de\r Ci\u00e8ncies Experimentals i de la Salut, Universitat Pompeu Fabra,\r C\/Dr. Aiguader 80, 08003 Barcelona, Spain; and Medical\r Research Council Clinical Sciences Centre, Du Cane Road, London W12\r 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Valverde","sequence":"additional","affiliation":[{"name":"Unitat de Senyalitzaci\u00f3 Cel\u00b7lular, Departament de\r Ci\u00e8ncies Experimentals i de la Salut, Universitat Pompeu Fabra,\r C\/Dr. Aiguader 80, 08003 Barcelona, Spain; and Medical\r Research Council Clinical Sciences Centre, Du Cane Road, London W12\r 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,4,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.S3"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2475911"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90148-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.S23"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.S145"},{"key":"e_1_3_3_6_2","first-page":"191","volume-title":"Cellular and Molecular Physiology of Cell Volume Regulation","author":"MacLeod R J","year":"1994","unstructured":"R J MacLeod Cellular and Molecular Physiology of Cell Volume Regulation, ed K Strange (CRC, Boca Raton), pp. 191\u2013213 (1994)."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00823.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.045bi.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00757.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.20.9038"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000016365"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.264.5.C1219"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.20.5.3243"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000633200"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90263-C"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374290"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.21.11651"},{"key":"e_1_3_3_19_2","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J","year":"1989","unstructured":"J Sambrook, E F Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. 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