Pathophysiological significance of the two-pore domain K+ channel K2P5.1 in splenic CD4+CD25- T cell subset from a chemically-induced murine inflammatory bowel disease model

• Main Authors: Sawa eNakakura, Miki eMatsui, Aya eSato, Mizuki eIshii, Kyoko eEndo, Sayaka eMuragishi, Miki eMurase, Hiroaki eKito, Hiroki eNiguma, Natsumi eKurokawa, Masanori eFujii, Masatake eAraki, Kimi eAraki, Susumu eOhya
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2015-10-01
• Series: Frontiers in Physiology
• Subjects: inflammatory bowel disease; Ca2+ influx; CD4+ T cell; Cytokine expression; background K+ channel; K2P5.1
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fphys.2015.00299/full

The alkaline pH-activated, two-pore domain K+ channel K2P5.1 (also known as TASK2/KCNK5) plays an important role in maintaining the resting membrane potential, and contributes to the control of Ca2+ signaling in several types of cells. Recent studies highlighted the potential role of the K2P5.1 K+ channel in the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The aim of the present study was to elucidate the pathological significance of the K2P5.1 K+ channel in inflammatory bowel disease (IBD). The degrees of colitis, colonic epithelial damage, and colonic inflammation were quantified in the dextran sulfate sodium-induced mouse IBD model by macroscopic and histological scoring systems. The expression and functional activity of K2P5.1 in splenic CD4+ T cells were measured using real-time PCR, Western blot, and fluorescence imaging assays. A significant increase was observed in the expression of K2P5.1 in the splenic CD4+ T cells of the IBD model. Concomitant with this increase, the hyperpolarization response induced by extracellular alkaline pH was significantly larger in the IBD model with the corresponding intracellular Ca2+ rises. The expression of K2P5.1 was higher in CD4+CD25- T cells than in CD4+CD25+ regulatory T cells. The knockout of K2P5.1 in mice significantly suppressed the disease responses implicated in the IBD model. Alternations in intracellular Ca2+ signaling following the dysregulated expression of K2P5.1 were associated with the disease pathogenesis of IBD. The results of the present study suggest that the K2P5.1 K+ channel in CD4+CD25- T cell subset is a potential therapeutic target and biomarker for IBD.