{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:55:28Z","timestamp":1790506528381,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T00:00:00Z","timestamp":1437955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01DE017102"],"award-info":[{"award-number":["5R01DE017102"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Calcium\u2010activated chloride channel (CaCC) plays an important role in modulating epithelial secretion. It has been suggested that in salivary tissues, sustained fluid secretion is dependent on Ca<jats:sup>2+<\/jats:sup> influx that activates ion channels such as CaCC to initiate Cl<jats:sup>\u2212<\/jats:sup> efflux. However direct evidence as well as the molecular identity of the Ca<jats:sup>2+<\/jats:sup> channel responsible for activating CaCC in salivary tissues is not yet identified. Here we provide evidence that in human salivary cells, an outward rectifying Cl<jats:sup>\u2212<\/jats:sup> current was activated by increasing [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, which was inhibited by the addition of pharmacological agents niflumic acid (NFA), an antagonist of CaCC, or T16Ainh\u2010A01, a specific TMEM16a inhibitor. Addition of thapsigargin (Tg), that induces store\u2010depletion and activates TRPC1\u2010mediated Ca<jats:sup>2+<\/jats:sup> entry, potentiated the Cl<jats:sup>\u2212<\/jats:sup> current, which was inhibited by the addition of a non\u2010specific TRPC channel blocker SKF96365 or removal of external Ca<jats:sup>2+<\/jats:sup>. Stimulation with Tg also increased plasma membrane expression of TMEM16a protein, which was also dependent on Ca<jats:sup>2+<\/jats:sup> entry. Importantly, in salivary cells, TRPC1 silencing, but not that of TRPC3, inhibited CaCC especially upon store depletion. Moreover, primary acinar cells isolated from submandibular gland also showed outward rectifying Cl<jats:sup>\u2212<\/jats:sup> currents upon increasing [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. These Cl<jats:sup>\u2212<\/jats:sup> currents were again potentiated with the addition of Tg, but inhibited in the presence of T16Ainh\u2010A01. Finally, acinar cells isolated from the submandibular glands of TRPC1 knockout mice showed significant inhibition of the outward Cl<jats:sup>\u2212<\/jats:sup> currents without decreasing TMEM16a expression. Together the data suggests that Ca<jats:sup>2+<\/jats:sup> entry via the TRPC1 channels is essential for the activation of CaCC. J. Cell. Physiol. 9999: 2848\u20132856, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25017","type":"journal-article","created":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T12:02:08Z","timestamp":1429617728000},"page":"2848-2856","source":"Crossref","is-referenced-by-count":50,"title":["TRPC1 regulates calcium\u2010activated chloride channels in salivary gland cells"],"prefix":"10.1002","volume":"230","author":[{"given":"Yuyang","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, School of Medicine Health Sciences University of North Dakota Grand Forks North Dakota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Birnbaumer","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, NIHES NIH, Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brij 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