title: [Physiological Role of K(+) Channels in the Regulation of T Cell Function].
abstract: Potassium ion (K(+)) channels play an important role in the modulation of calcium ion (Ca(2+)) signaling via control of the membrane potential. In T-lymphocytes, the voltage-gated K(+) channel, KV1.3, and the intermediate-conductance Ca(2+)-activated K(+) channel, KCa3.1, predominantly contribute to K(+) conductance, and are responsible for cell proliferation, differentiation, apoptosis and infiltration. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, afflicts more than 0.1% of the population worldwide. In the chemically-induced IBD model mouse, an increase in KCa3.1 activity was observed in mesenteric lymph node CD4(+) T-lymphocytes, concomitant with an upregulation of KCa3.1 and a positive KCa3.1 regulator, NDPK-B. Pharmacological blockade of the KCa3.1 K(+) channel by TRAM-34 and/or ICA17043 elicited 1) a significant decrease in IBD severity, as assessed by diarrhea, visible fecal blood, inflammation and crypt damage of the colon; and 2) restoration of the expression levels of KCa3.1 and Th1 cytokines in CD4(+) T-lymphocytes in the IBD model. Recent studies have indicated the impact of K2P5.1 upregulation in T lymphocytes on the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The K2P5.1 K(+) channel is therefore highlighted as a potent therapeutic target in managing the pathogenesis of autoimmune diseases. Alternatively, pre-mRNA splicing of ion channels is associated with the development and progression of various diseases, including autoimmune diseases. Therefore, mRNA-splicing mechanisms underlying the transcriptional regulation of K2P5.1 K(+) channels may be a new strategic therapeutic target for autoimmune and inflammatory diseases.
authors.affiliation: Department of Pharmacology, Kyoto Pharmaceutical University.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohya
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000628:therapy; D020013:Calcium Signaling / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000628:therapy; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D058990:Molecular Targeted Therapy; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000502:physiology*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger