title: Role of the K(Ca)3.1 K+ channel in auricular lymph node CD4+ T-lymphocyte function of the delayed-type hypersensitivity model.
abstract: OBJECTIVE
  The intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) modulates the Ca(2+) response through the control of the membrane potential in the immune system. We investigated the role of K(Ca)3.1 on the pathogenesis of delayed-type hypersensitivity (DTH) in auricular lymph node (ALN) CD4(+) T-lymphocytes of oxazolone (Ox)-induced DTH model mice.
  
  
  METHODS
  The expression patterns of K(Ca)3.1 and its possible transcriptional regulators were compared among ALN T-lymphocytes of three groups [non-sensitized (Ox-/-), Ox-sensitized, but non-challenged (Ox+/-) and Ox-sensitized and -challenged (Ox+/+)] using real-time polymerase chain reaction, Western blotting and flow cytometry. KCa 3.1 activity was measured by whole-cell patch clamp and the voltage-sensitive dye imaging. The effects of K(Ca)3.1 blockade were examined by the administration of selective K(Ca)3.1 blockers.
  
  
  RESULTS
  Significant up-regulation of K(Ca)3.1a was observed in CD4(+) T-lymphocytes of Ox+/- and Ox+/+, without any evident changes in the expression of the dominant-negative form, K(Ca)3.1b. Negatively correlated with this, the repressor element-1 silencing transcription factor (REST) was significantly down-regulated. Pharmacological blockade of K(Ca)3.1 resulted in an accumulation of the CD4(+) T-lymphocytes of Ox+/+ at the G0/G1 phase of the cell cycle, and also significantly recovered not only the pathogenesis of DTH, but also the changes in the K(Ca)3.1 expression and activity in the CD4(+) T-lymphocytes of Ox+/- and Ox+/+.
  
  
  CONCLUSIONS
  The up-regulation of K(Ca)3.1a in conjunction with the down-regulation of REST may be involved in CD4(+) T-lymphocyte proliferation in the ALNs of DTH model mice; and K(Ca)3.1 may be an important target for therapeutic intervention in allergy diseases such as DTH.
authors.affiliation: Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohya
authors.forename: Erina
authors.initials: E
authors.lastname: Nakamura
authors.forename: Sayuri
authors.initials: S
authors.lastname: Horiba
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kito
authors.forename: Miki
authors.initials: M
authors.lastname: Matsui
authors.forename: Hisao
authors.initials: H
authors.lastname: Yamamura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Imaizumi
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D004195:Disease Models, Animal; D054644:Ear Auricle / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D010081:Oxazolone; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012097:Repressor Proteins / Q000276:immunology; D000099229:RE1-Silencing Transcription Factor
chemical_list: D000276:Adjuvants, Immunologic; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D010081:Oxazolone; D026902:Potassium Channel Blockers; D011720:Pyrazoles; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C496925:Kcnn4 protein, mouse; C411671:TRAM 34