{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:10:41Z","timestamp":1790485841102,"version":"4.1.0"},"reference-count":54,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2003,8]]},"abstract":"<jats:p>Pancreatic duct cells express a Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>-activated Cl<jats:sup>-<\/jats:sup>conductance (CaCC), upregulation of which may be beneficial to patients with cystic fibrosis. Here, we report that HPAF, a human pancreatic ductal adenocarcinoma cell line that expresses CaCC, develops into a high-resistance, anion-secreting epithelium. Mucosal ATP (50 \u03bcM) caused a fourfold increase in short-circuit current ( I<jats:sub>sc<\/jats:sub>), a hyperpolarization of transepithelial potential difference (from -4.9 \u00b1 0.73 to -8.5 \u00b1 0.84 mV), and a fall in resistance to less than one-half of resting values. The effects of ATP were inhibited by mucosal niflumic acid (100 \u03bcM), implicating an apical CaCC in the response. RT-PCR indicated expression of hClC-2, hClC-3, and hClC-5, but surprisingly not hCLCA-1 or hCLCA-2. K<jats:sup>+<\/jats:sup>channel activity was necessary to maintain the ATP-stimulated I<jats:sub>sc<\/jats:sub>. Using a pharmacological approach, we found evidence for two types of K<jats:sup>+<\/jats:sup>channels in the mucosal and serosal membranes of HPAF cells, one activated by chlorzoxazone (500 \u03bcM) and sensitive to clotrimazole (30 \u03bcM), as well as one blocked by clofilium (100 \u03bcM) but not chromanol 293B (5 \u03bcM). RT-PCR indicated expression of the Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>channel KCNN4, as well as the acid-sensitive, four transmembrane domain, two pore K<jats:sup>+<\/jats:sup>channel, KCNK5 (hTASK-2). Western blot analysis verified the expression of CLC channels, as well as KCNK5. We conclude that HPAF will be a useful model system for studying channels pertinent to anion secretion in human pancreatic duct cells.<\/jats:p>","DOI":"10.1152\/ajpcell.00509.2002","type":"journal-article","created":{"date-parts":[[2013,5,14]],"date-time":"2013-05-14T00:15:31Z","timestamp":1368490531000},"page":"C433-C445","source":"Crossref","is-referenced-by-count":76,"title":["Characterization of vectorial chloride transport pathways in the human pancreatic duct adenocarcinoma cell line HPAF"],"prefix":"10.1152","volume":"285","author":[{"given":"Peying","family":"Fong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry E.","family":"Argent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Guggino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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acid-sensitive K+channel TASK-2 (KCNK5) by changes in cell volume.J Biol Chem276: 43166\u201343174, 2001.","DOI":"10.1074\/jbc.M107192200"},{"key":"REF36","doi-asserted-by":"crossref","unstructured":"Novak Iand Greger R.Effect of bicarbonate on potassium conductance of isolated perfused rat pancreatic ducts.Pfl\u00fcgers Arch419: 76\u201383, 1991.","DOI":"10.1007\/BF00373750"},{"key":"REF37","doi-asserted-by":"crossref","unstructured":"Novak Iand Hansen MR.Where have all the Na+channels gone? 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SM, Gelder FB, Rado TA, and Frizzell RA.A cystic fibrosis pancreatic adenocarcinoma cell line.Proc Natl Acad Sci USA87: 4012\u20134016, 1990.","DOI":"10.1073\/pnas.87.10.4012"},{"key":"REF43","doi-asserted-by":"crossref","unstructured":"Schroeder BC, Hechenberger M, Weinreich F, Kubisch C, and Jentsch TJ.KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents.J Biol Chem275: 24089\u201324095, 2000.","DOI":"10.1074\/jbc.M003245200"},{"key":"REF44","doi-asserted-by":"crossref","unstructured":"Schwake M, Friedrich T, and Jentsch TJ.An internalization signal in ClC-5, an endosomal Cl-channel mutated in Dent's disease.J Biol Chem276: 12049\u201312054, 2001.","DOI":"10.1074\/jbc.M010642200"},{"key":"REF45","doi-asserted-by":"crossref","unstructured":"Sewell WAand Young JA.Secretion of electrolytes by the pancreas of the anaesthetized rat.J Physiol252: 379\u2013396, 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2001.","DOI":"10.1016\/S0896-6273(01)00189-1"},{"key":"REF49","doi-asserted-by":"crossref","unstructured":"Thomas EJ, Gabriel SE, Makhlina M, Hardy SP, and Lethem MI.Expression of nucleotide-regulated Cl-currents in CF and normal mouse tracheal epithelial cell lines.Am J Physiol Cell Physiol279: C1578\u2013C1586, 2000.","DOI":"10.1152\/ajpcell.2000.279.5.C1578"},{"key":"REF50","doi-asserted-by":"crossref","unstructured":"Wills NKand Fong P.ClC chloride channels in epithelia: recent progress and remaining puzzles.News Physiol Sci16: 161\u2013166, 2001.","DOI":"10.1152\/physiologyonline.2001.16.4.161"},{"key":"REF51","doi-asserted-by":"crossref","unstructured":"Winpenny JP, Harris A, Hollingsworth MA, Argent BE, and Gray MA.Calcium-activated chloride conductance in a pancreatic adenocarcinoma cell line of ductal origin (HPAF) and in freshly isolated human pancreatic duct cells.Pfl\u00fcgers Arch435: 796\u2013803, 1998","DOI":"10.1007\/s004240050586"},{"key":"REF52","doi-asserted-by":"crossref","unstructured":"Winpenny JP, Verdon B, McAlroy HL, Colledge WH, Ratcliff R, Evans MJ, Gray MA, and Argent BE.Calcium-activated chloride conductance is not increased in pancreatic duct cells of CF mice.Pfl\u00fcgers Arch430: 26\u201333, 1995.","DOI":"10.1007\/BF00373836"},{"key":"REF53","doi-asserted-by":"crossref","unstructured":"Wong PYD.Do seminiferous tubules secrete a fluid rich in KHCO3?J Physiol542: 335, 2002.","DOI":"10.1113\/jphysiol.2002.020511"},{"key":"REF54","doi-asserted-by":"crossref","unstructured":"Zsembery \u00c1, Strazzabosco M and Graf J.Ca2+-activated Cl-channels can substitute for CFTR in stimulation of pancreatic duct bicarbonate secretion.FASEB J14: 2345\u20132356, 2000.","DOI":"10.1096\/fj.99-0509com"}],"container-title":["American Journal of Physiology-Cell 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