title: ClC-3 is a candidate of the channel proteins mediating acid-activated chloride currents in nasopharyngeal carcinoma cells.
abstract: Acid-activated chloride currents have been reported in several cell types and may play important roles in regulation of cell function. However, the molecular identities of the channels that mediate the currents are not defined. In this study, activation of the acid-induced chloride current and the possible candidates of the acid-activated chloride channel were investigated in human nasopharyngeal carcinoma cells (CNE-2Z). A chloride current was activated when extracellular pH was reduced to 6.6 from 7.4. However, a further decrease of extracellular pH to 5.8 inhibited the current. The current was weakly outward-rectified and was suppressed by hypertonicity-induced cell shrinkage and by the chloride channel blockers 5-nitro-2-3-phenylpropylamino benzoic acid (NPPB), tamoxifen, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate (DIDS). The permeability sequence of the channel to anions was I(-) > Br(-) > Cl(-) > gluconate(-). Among the ClC chloride channels, ClC-3 and ClC-7 were strongly expressed in CNE-2Z cells. Knockdown of ClC-3 expression with ClC-3 small interfering (si)RNA prevented the activation of the acid-induced current, but silence of ClC-7 expression with ClC-7 siRNA did not significantly affect the current. The results suggest that the chloride channel mediating the acid-induced chloride current was volume sensitive. ClC-3 is a candidate of the channel proteins that mediate or regulate the acid-activated chloride current in nasopharyngeal carcinoma cells.
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China. wangliweic@sohu.com
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.forename: Wenbo
authors.initials: W
authors.lastname: Ma
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.forename: Dong
authors.initials: D
authors.lastname: Ye
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Shanwen
authors.initials: S
authors.lastname: Liu
authors.forename: Huarong
authors.initials: H
authors.lastname: Li
authors.forename: Wanhong
authors.initials: W
authors.lastname: Zuo
authors.forename: Bingxue
authors.initials: B
authors.lastname: Li
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D002277:Carcinoma; D045744:Cell Line, Tumor; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D034622:RNA Interference; D034741:RNA, Small Interfering; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C097540:CLCN7 protein, human; D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D009579:Nitrobenzoates; D034741:RNA, Small Interfering; D013629:Tamoxifen; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid