{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:17:21Z","timestamp":1790561841942,"version":"4.1.0"},"reference-count":190,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["25CDA1435154"],"award-info":[{"award-number":["25CDA1435154"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24CDA1269410"],"award-info":[{"award-number":["24CDA1269410"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endothelial cells (ECs) line the lumen of blood and lymphatic vessels and form capillaries. ECs are exposed to a diverse array of physiological stimuli and regulate a multitude of functions, including contractility, blood coagulation, leukocyte recruitment, wound healing, angiogenesis and the blood\u2013tissue exchange of gases, metabolites and macromolecules. Chloride (Cl<jats:sup>\u2212<\/jats:sup>) is the principal anion in ECs, with its intracellular concentration ([Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub>) regulated by pumps, transporters and channels. ECs express the Cl<jats:sup>\u2212<\/jats:sup> channel proteins transmembrane protein 16A (TMEM16A, ANO1), leucine\u2010rich repeat (LRR)\u2010containing 8 (LRRC8), CLCs and cystic fibrosis transmembrane conductance regulator (CFTR), which are plasma membrane proteins, and CLICs, which are located on intracellular organelles. Cl<jats:sup>\u2212<\/jats:sup> channels can regulate both the membrane potential and [Cl<jats:sup>\u2212<\/jats:sup>]<jats:sub>i<\/jats:sub> of ECs to modulate physiological functions. Recent evidence indicates that intracellular Cl<jats:sup>\u2212<\/jats:sup> is a physiological second messenger that regulates the activity of WNK (i.e. with\u2010no\u2010lysine) kinases in ECs. Impaired functions of Cl<jats:sup>\u2013<\/jats:sup> channels in ECs have also been associated with diseases such as hypertension, atherosclerosis, cancer and lung oedema. This review discusses the current knowledge of individual Cl<jats:sup>\u2212<\/jats:sup> channel types that are expressed in ECs, as well as their signalling mechanisms, physiological functions and pathological relevance.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70150-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1113\/jp287608","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T05:36:45Z","timestamp":1759815405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Chloride channels in endothelial cells"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1831-7842","authenticated-orcid":false,"given":"Alejandro","family":"Mata\u2010Daboin","sequence":"first","affiliation":[{"name":"Department of Physiology University of Tennessee Health Science Center  Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa A. C.","family":"Garrud","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Tennessee Health Science Center  Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1505-3335","authenticated-orcid":false,"given":"Jonathan H.","family":"Jaggar","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Tennessee Health Science Center  Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"issue":"7","key":"e_1_2_2_2_1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/bies.201100173","article-title":"LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell\u2010cell communication","volume":"34","author":"Abascal F.","year":"2012","journal-title":"BioEssays"},{"issue":"20","key":"e_1_2_2_3_1","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1161\/CIRCULATIONAHA.110.972745","article-title":"Proteomic analysis of lung tissues from patients with pulmonary arterial hypertension","volume":"122","author":"Abdul\u2010Salam V. 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