{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:14:03Z","timestamp":1791278043904,"version":"4.1.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,1,2]]},"abstract":"<jats:p>\n                    Anoctamin 1 (ANO1)\/transmembrane protein 16A (TMEM16A) is a calcium-activated anion channel that may play a role in HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    secretion in epithelial cells. Here, we report that the anion selectivity of ANO1 is dynamically regulated by the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/calmodulin complex. Whole-cell current measurements in HEK 293T cells indicated that ANO1 becomes highly permeable to HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    at high [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    . Interestingly, this result was not observed in excised patches, indicating the involvement of cytosolic factors in this process. Further studies revealed that the direct association between ANO1 and calmodulin at high [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    is responsible for changes in anion permeability. Calmodulin physically interacted with ANO1 in a [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    -dependent manner, and addition of recombinant calmodulin to the cytosolic side of excised patches reversibly increased P\n                    <jats:sub>HCO3<\/jats:sub>\n                    \/P\n                    <jats:sub>Cl<\/jats:sub>\n                    . In addition, the high [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    -induced increase in HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    permeability was reproduced in mouse submandibular gland acinar cells, in which ANO1 plays a critical role in fluid secretion. These results indicate that the HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    permeability of ANO1 can be dynamically modulated and that ANO1 may play an important role in cellular HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    transport, especially in transepithelial HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    secretion.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1211594110","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T00:24:36Z","timestamp":1355790276000},"page":"360-365","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":160,"title":["Dynamic modulation of ANO1\/TMEM16A HCO\n                    <sub>3<\/sub>\n                    <sup>\u2212<\/sup>\n                    permeability by Ca\n                    <sup>2+<\/sup>\n                    \/calmodulin"],"prefix":"10.1073","volume":"110","author":[{"given":"Jinsei","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, and"},{"name":"Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 120-752, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hyun","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Dongguk University, Gyeongju 780-714, Korea; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uhtaek","family":"Oh","sequence":"additional","affiliation":[{"name":"Sensory Research Center, Creative Research Initiatives, College of Pharmacy, Seoul National University, Seoul 151-742, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo-Heon","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 120-752, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Goo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,12,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.032003.154341"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.068544"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07313"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1163518"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.09.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903304106"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.116.6.825"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200810122"},{"key":"e_1_3_3_9_2","first-page":"77","article-title":"HCO3\n                  - transport in a mathematical model of the pancreatic ductal epithelium","volume":"176","author":"Sohma Y","year":"2000","unstructured":"Y Sohma, MA Gray, Y Imai, BE Argent, HCO3- transport in a mathematical model of the pancreatic ductal epithelium. 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