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This inward-rectifying Cl<jats:sup>\u2212<\/jats:sup>current is activated by hyperpolarization and elevated intracellular Cl<jats:sup>\u2212<\/jats:sup>concentration. Here we show that ClC-2 immunolocalized to the basolateral region of acinar and duct cells in mouse salivary glands, whereas its expression was most robust in granular and striated duct cells. Consistent with this observation, nearly 10-fold larger ClC-2-like currents were observed in granular duct cells than the acinar cells obtained from submandibular glands. The loss of inward-rectifying Cl<jats:sup>\u2212<\/jats:sup>current in cells from Clcn2<jats:sup>\u2212\/\u2212<\/jats:sup>mice confirmed the molecular identity of the channel responsible for these currents as ClC-2. Nevertheless, both in vivo and ex vivo fluid secretion assays failed to identify significant changes in the ion composition, osmolality, or salivary flow rate of Clcn2<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Additionally, neither a compensatory increase in Cftr Cl<jats:sup>\u2212<\/jats:sup>channel protein expression nor in Cftr-like Cl<jats:sup>\u2212<\/jats:sup>currents were detected in Clcn2 null mice, nor did it appear that ClC-2 was important for blood-organ barrier function. We conclude that ClC-2 is the inward-rectifying Cl<jats:sup>\u2212<\/jats:sup>channel in duct cells, but its expression is not apparently required for the ion reabsorption or the barrier function of salivary ductal epithelium.<\/jats:p>","DOI":"10.1152\/ajpgi.90384.2008","type":"journal-article","created":{"date-parts":[[2008,9,19]],"date-time":"2008-09-19T00:55:09Z","timestamp":1221785709000},"page":"G1058-G1067","source":"Crossref","is-referenced-by-count":33,"title":["<i>Clcn2<\/i>encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands"],"prefix":"10.1152","volume":"295","author":[{"given":"Victor G.","family":"Romanenko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuji","family":"Nakamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo A.","family":"Catal\u00e1n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireya","family":"Gonzalez-Begne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George J.","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasna","family":"Jaramillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco V.","family":"Sep\u00falveda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos D.","family":"Figueroa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Melvin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005630429723"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021149"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.10.015"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.278.6.L1248"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0338-07.2007"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.6.1289"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00158.2002"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.01.010"},{"key":"R9","unstructured":"Cook DI, Van Lennep EW, Roberts ML, Young JA.Secretion by the Major Salivary Glands. 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