title: Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR).
abstract: The broadly expressed volume-sensitive outwardly rectifying anion channel (VSOR, also called VRAC) plays essential roles in cell survival and death. Recent findings have suggested that LRRC8A is a core component of VSOR in human cells. In the present study, VSOR currents were found to be largely reduced by siRNA against LRRC8A in mouse C127 cells as well. In contrast, LRRC8A knockdown never affected activities of 4 other types of anion channel activated by acid, Ca2+, patch excision or cAMP. While cisplatin-resistant KCP-4 cells poorly expressed endogenous VSOR activity, molecular expression levels of LRRC8A, LRRC8D and LRRC8E were indistinguishable between VSOR-deficient KCP-4 cells and the parental VSOR-rich KB cells. Furthermore, overexpression of LRRC8A alone or together with LRRC8D or LRRC8E in KCP-4 cells failed to restore VSOR activity. These results show that deficiency of VSOR currents in KCP-4 cells is not due to insufficient expression of the LRRC8A/D/E gene, suggesting an essential involvement of some other factor(s), and indicate that further study is required to better understand the complexities of the molecular determinants of VSOR, including the precise role of LRRC8 proteins.
authors.affiliation: a International Collaborative Research Project, National Institute for Physiological Sciences , Okazaki , Japan.|b Division of Cell Signaling , National Institute for Physiological Sciences , National Institutes of Natural Sciences , Okazaki , Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Okada
authors.affiliation: a International Collaborative Research Project, National Institute for Physiological Sciences , Okazaki , Japan.
authors.forename: Md Rafiqul
authors.initials: MR
authors.lastname: Islam
authors.affiliation: a International Collaborative Research Project, National Institute for Physiological Sciences , Okazaki , Japan.|c Laboratory of Molecular Physiology , Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences , Tashkent , Uzbekistan.
authors.forename: Nargiza A
authors.initials: NA
authors.lastname: Tsiferova
authors.affiliation: d SOKENDAI (The Graduate University for Advanced Studies) , Shonan Village, Hayama , Kanagawa , Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okada
authors.affiliation: a International Collaborative Research Project, National Institute for Physiological Sciences , Okazaki , Japan.|c Laboratory of Molecular Physiology , Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences , Tashkent , Uzbekistan.
authors.forename: Ravshan Z
authors.initials: RZ
authors.lastname: Sabirov
mesh_terms: D000818:Animals; D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015640:Ion Channel Gating; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D018118:Chloride Channels; C485976:LRRC8A protein, human; C000589080:LRRC8A protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: LRRC8; VSOR; anion channel; cisplatin resistance; volume-sensitive