{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:53:34Z","timestamp":1790873614770,"version":"4.1.0"},"reference-count":52,"publisher":"Canadian Science Publishing","issue":"6","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochem. Cell Biol."],"published-print":{"date-parts":[[2004,12,1]]},"abstract":"<jats:p> In mammalian nonpigmented ciliary epithelial (NPE) cells, hyposmotic stimulation leading to cell swelling activates an outwardly rectifying Cl<jats:sup>\u0096<\/jats:sup> conductance (I<jats:sub>Cl,swell<\/jats:sub>), which, in turn, results in regulatory volume decrease. The aim of this study was to determine whether increased trafficking of intracellular ClC-3 Cl channels to the plasma membrane could contribute to the I<jats:sub>Cl,swell<\/jats:sub> following hyposmotic stimulation. Our results demonstrate that hyposmotic stimulation reversibly activates an outwardly rectifying Cl<jats:sup>\u0096<\/jats:sup> current that is inhibited by phorbol-12-dibutyrate and niflumic acid. Transfection with ClC-3 antisense, but not sense, oligonucleotides reduced ClC-3 expression as well as I<jats:sub>Cl,swell<\/jats:sub>. Intracellular dialysis with 2 different ClC-3 antibodies abolished activation of I<jats:sub>Cl,swell<\/jats:sub>. Immunofluorescence microscopy showed that hyposmotic stimulation increased ClC-3 immunoreactivity at the plasma membrane. To determine whether this increased expression of ClC-3 at the plasma membrane could be due to increased vesicular trafficking, we examined membrane dynamics with the fluorescent membrane dye FM1-43. Hyposmotic stimulation rapidly increased the rate of exocytosis, which, along with I<jats:sub>Cl,swell<\/jats:sub>, was inhibited by the phosphoinositide-3-kinase inhibitor wortmannin and the microtubule disrupting agent, nocodazole. These findings suggest that ClC-3 channels contribute to I<jats:sub>Cl,swell<\/jats:sub> following hyposmotic stimulation through increased trafficking of channels to the plasma membrane.Key words: ClC-3, NPE, cell swelling, membrane trafficking, ciliary body epithelium. <\/jats:p>","DOI":"10.1139\/o04-107","type":"journal-article","created":{"date-parts":[[2005,1,26]],"date-time":"2005-01-26T19:54:27Z","timestamp":1106769267000},"page":"708-718","source":"Crossref","is-referenced-by-count":39,"title":["Hyposmotic activation of I<sub>Cl,swell<\/sub> in rabbit nonpigmented ciliary epithelial cells involves increased ClC-3 trafficking to the plasma membrane"],"prefix":"10.1139","volume":"82","author":[{"given":"John P","family":"Vessey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanjuan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine AB","family":"Jollimore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly T","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Coca-Prados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie EM","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"p_1\/p_1_1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0955-0674(03)00084-X","volume":"15","author":"Altschuler Y.","year":"2003","journal-title":"Curr. 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