title: Expression of TASK-2 and its upregulation by B cell receptor stimulation in WEHI-231 mouse immature B cells.
abstract: Stimulation of B cell receptors (BCR ligation) induces apoptosis of immature B cells, which is critical to the elimination of self-reactive clones. In the mouse immature B cell line WEHI-231, the authors previously reported two types of background K+ channels with large (~300 pS, LK(bg)) and medium (~100 pS, MK(bg)) conductance in divalent cation-free conditions. While the authors have recently identified LK(bg) as TREK-2, the molecular nature of MK(bg) is unknown yet. In the present study, the authors found that BCR ligation markedly increased the background K+ conductance of WEHI-231. A single-channel study revealed that MK(bg) activity is increased by BCR ligation and that the biophysical properties (unitary conductance and pH sensitivity) of MK(bg) are consistent with those of TWIK-related acid-sensitive K+ channel 2 (TASK-2). The expression of TASK-2 and its upregulation by BCR ligation were confirmed by RT-PCR and immunoblot assays in WEHI-231. The BCR ligation-induced increase of K+ current was prevented by calcineurin inhibitors (cyclosporine A or FK506), and also by TASK-2-specific small interfering RNA (siRNA) transfection (si-TASK-2). Furthermore, si-TASK-2 attenuated the apoptosis of WEHI-231 caused by BCR ligation. TASK-2 activity and its mRNA were also confirmed in the primary splenic B cells of mouse. Summarizing, the authors report for the first time the expression of TASK-2 in B cells and surmise that the upregulation of TASK-2 by BCR ligation is associated with the apoptosis of immature B cells.
authors.affiliation: Dept. of Physiology, Ischemia/Hypoxia Disease Institute, Seoul National Univ. College of Medicine, Seoul, Korea. sjoonkim@snu.ac.kr
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Nam
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Shin
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zheng
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Kyung Sun
authors.initials: KS
authors.lastname: Park
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D065095:Calcineurin Inhibitors; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D051379:Mice; D024683:Potassium Channels, Tandem Pore Domain / Q000096:biosynthesis* / Q000235:genetics; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism* / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism* / Q000502:physiology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D065095:Calcineurin Inhibitors; C498739:Kcnk5 protein, mouse; D024683:Potassium Channels, Tandem Pore Domain; D034741:RNA, Small Interfering; D011947:Receptors, Antigen, B-Cell; D016572:Cyclosporine; D016559:Tacrolimus