title: The AQP-3 water channel is a pivotal modulator of glycerol-induced chloride channel activation in nasopharyngeal carcinoma cells.
abstract: Aquaporin (AQP) and chloride channels are ubiquitous in virtually all living cells, playing pivotal roles in cell proliferation, migration and apoptosis. We previously reported that AQP-3 aquaglyceroporin and ClC-3 chloride channels could form complexes to regulate cell volume in nasopharyngeal carcinoma cells. In this study, the roles of AQP-3 in their hetero-complexes were further investigated. Glycerol entered the cells via AQP-3 and induced two different Cl(-) currents through cell swelling-dependent or -independent pathways. The swelling-dependent Cl(-) current was significantly inhibited by pretreatment with CuCl2 and AQP-3-siRNA. After siRNA-induced AQP-3 knock-down, the 140 mM glycerol isoosmotic solution swelled cells by 22% (45% in AQP-3-intact cells) and induced a smaller Cl(-) current; this current was smaller than that activated by 8% cell volume swelling, which induced by the 140 mM glycerol hyperosmotic solution in AQP-3-intact cells. This suggests that the interaction between AQP-3 and ClC-3 plays an important role in cell volume regulation and that AQP-3 may be a modulator that opens volume-regulated chloride channels. The swelling-independent Cl(-) current, which was activated by extracellular glycerol, was reduced by CuCl2 and AQP-3-siRNA pretreatment. Dialyzing glycerol into cells via the pipette directly induced the swelling-independent Cl(-) current; however this current was blocked by AQP-3 down-regulation, suggesting AQP-3 is essential for the opening of chloride channels. In conclusion, AQP-3 is the pathway for water, glycerol and other small solutes to enter cells, and it may be an essential modulator for the gating of chloride channels.
authors.affiliation: Department of Pathology, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: zhf19841011@126.com.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China; Department of Pathophysiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Academic Affairs, Guangzhou Medical University, Guangzhou 510182, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China; Department of Pathophysiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China; Department of Pathophysiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Shanwen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China; Department of Pathophysiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China; Department of Pathophysiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China; Department of Pathophysiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: twangliwei@jnu.edu.cn.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: tchenlixin@jnu.edu.cn.
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
mesh_terms: D051400:Aquaporin 3 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects; D065101:Chloride Channel Agonists / Q000494:pharmacology*; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005990:Glycerol / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D065101:Chloride Channel Agonists; D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D034741:RNA, Small Interfering; D051400:Aquaporin 3; D005990:Glycerol
keywords: AQP-3; Chloride channels; ClC-3; Glycerol; Protein–protein interaction