title: Distinct contributions of LRRC8A and its paralogs to the VSOR anion channel from those of the ASOR anion channel.
abstract: Volume- and acid-sensitive outwardly rectifying anion channels (VSOR and ASOR) activated by swelling and acidification exhibit voltage-dependent inactivation and activation time courses, respectively. Recently, LRRC8A and some paralogs were shown to be essentially involved in the activity and inactivation kinetics of VSOR currents in human colonic HCT116 cells. In human cervix HeLa cells, here, inactivation of VSOR currents was found to become accelerated by RNA silencing only of LRRC8A but never decelerated by that of any LRRC8 isoform. These data suggest that LRRC8A is associated with the deceleration mechanism of VSOR inactivation, while none of LRRC8 members is related to the acceleration mechanism. Activation kinetics of ASOR currents was unaffected by knockdown of any LRRC8 family member. Double, triple and quadruple gene-silencing studies indicated that combinatory expression of LRRC8A with LRRC8D and LRRC8C is essential for VSOR activity, whereas none of LRRC8 family members is involved in ASOR activity.
authors: a Japan Society for the Promotion of Science , Chiyoda-ku , Japan.|b Department of Cell Physiology , National Institute for Physiological Sciences, National Institutes of Natural Sciences , Okazaki , Japan.|c Department of Physiology, School of Medicine , Fukuoka University , Fukuoka , Japan.
authors: Kaori
authors: K
authors: Sato-Numata
authors: c Department of Physiology, School of Medicine , Fukuoka University , Fukuoka , Japan.
authors: Tomohiro
authors: T
authors: Numata
authors: c Department of Physiology, School of Medicine , Fukuoka University , Fukuoka , Japan.
authors: Ryuji
authors: R
authors: Inoue
authors: d International Collaborative Research Project, National Institute for Physiological Sciences , Okazaki , Japan.
authors: Ravshan Z
authors: RZ
authors: Sabirov
authors: e SOKENDAI (The Graduate University for Advanced Studies) , Hayama , Kanagawa , Japan.
authors: Yasunobu
authors: Y
authors: Okada
mesh_terms: D000838:Anions; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D000838:Anions; D007473:Ion Channels; C485976:LRRC8A protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering
keywords: ASOR; LRRC8; VRAC; VSOR; activation; anion channel; inactivation