{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:47:59Z","timestamp":1787510879210,"version":"build-2736575974"},"reference-count":60,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91732108"],"award-info":[{"award-number":["91732108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81500057"],"award-info":[{"award-number":["81500057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["GZR81701113"],"award-info":[{"award-number":["GZR81701113"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571088"],"award-info":[{"award-number":["31571088"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31872788"],"award-info":[{"award-number":["31872788"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Basic Research Project of Applied Basic Research Program of Hebei Province","award":["16967712D"],"award-info":[{"award-number":["16967712D"]}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/R003068\/1"],"award-info":[{"award-number":["BB\/R003068\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/R02104X\/1"],"award-info":[{"award-number":["BB\/R02104X\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hebei Province Department of Education Grant","award":["BJ2017004"],"award-info":[{"award-number":["BJ2017004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:p>\n                    The swelling-activated chloride current ( I\n                    <jats:sub>Cl,swell<\/jats:sub>\n                    ) is induced when a cell swells and plays a central role in maintaining cell volume in response to osmotic stress. The major contributor of I\n                    <jats:sub>Cl,swell<\/jats:sub>\n                    is the volume-regulated anion channel (VRAC). Leucine-rich repeat containing 8A (LRRC8A; SWELL1) was recently identified as an essential component of VRAC, but the mechanisms of VRAC activation are still largely unknown; moreover, other Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channels, such as anoctamin 1 (ANO1), were also suggested to contribute to I\n                    <jats:sub>Cl,swell<\/jats:sub>\n                    . In this present study, we investigated the roles of LRRC8A and ANO1 in activation of I\n                    <jats:sub>Cl,swell<\/jats:sub>\n                    ; we also explored the role of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    in I\n                    <jats:sub>Cl,swell<\/jats:sub>\n                    activation. We used a CRISPR\/Cas9 gene editing approach, electrophysiology, live fluorescent imaging, selective pharmacology, and other approaches to show that both LRRC8A and ANO1 can be activated by cell swelling in HEK293 cells. Yet, both channels contribute biophysically and pharmacologically distinct components to I\n                    <jats:sub>Cl,swell<\/jats:sub>\n                    , with LRRC8A being the major component. Cell swelling induced oscillatory Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients, and these Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals were required to activate both the LRRC8A- and ANO1-dependent components of I\n                    <jats:sub>Cl,swell<\/jats:sub>\n                    . Both I\n                    <jats:sub>Cl,swell<\/jats:sub>\n                    components required localized rather than global Ca\n                    <jats:sup>2+<\/jats:sup>\n                    for activation. Interestingly, while intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    was necessary and sufficient to activate ANO1, it was necessary but not sufficient to activate LRRC8A-mediated currents. Finally, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients linked to the I\n                    <jats:sub>Cl,swell<\/jats:sub>\n                    activation were mediated by the G protein-coupled receptor-independent PLC isoforms.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00507.2018","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T17:06:36Z","timestamp":1561568796000},"page":"C466-C480","source":"Crossref","is-referenced-by-count":31,"title":["Volume-regulated Cl\n                    <sup>\u2212<\/sup>\n                    current: contributions of distinct Cl\n                    <sup>\u2212<\/sup>\n                    channels and localized Ca\n                    <sup>2+<\/sup>\n                    signals"],"prefix":"10.1152","volume":"317","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5675-4712","authenticated-orcid":false,"given":"Yani","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"},{"name":"Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"},{"name":"Department of Pulmonary Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchao","family":"Men","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaona","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Gamper","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"},{"name":"School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hebei Medical University, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China"},{"name":"The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1159\/000335867"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.06.015"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.208173"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.010074"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-016-1862-1"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.277145"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.06.032"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1163518"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-013-9609-9"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4916"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704413"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0134-y"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.018770"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.206698"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.075622"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00328"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-3012-0_3"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2014.00219"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5419.1527"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2007"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.278887"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.29"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004184"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.38461"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.07.005"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-015-1767-4"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nature07842"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2297-08.2008"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41084"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1572-5"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.196253"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-014-9561-0"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.12.044"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1418840112"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(97)90064-6"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80983-6"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00725.2017"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.2003.01060.x"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6107(97)00021-7"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.273.3.C755"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.165076"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7245"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2010.09.013"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12450"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-015-1781-6"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201592409"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.024"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101264200"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1559-2"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.09.003"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70135-6"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04353-y"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.031"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050023"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.739342"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.143.2.501"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252826"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/nature07313"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3514"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200409161"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00507.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T11:44:05Z","timestamp":1718624645000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00507.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,1]]},"references-count":60,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,9,1]]}},"alternative-id":["10.1152\/ajpcell.00507.2018"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00507.2018","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,1]]}}}