AUTHOR=Nakakura Sawa , Matsui Miki , Sato Aya , Ishii Mizuki , Endo Kyoko , Muragishi Sayaka , Murase Miki , Kito Hiroaki , Niguma Hiroki , Kurokawa Natsumi , Fujii Masanori , Araki Masatake , Araki Kimi , Ohya Susumu TITLE=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 JOURNAL=Frontiers in Physiology VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2015.00299 DOI=10.3389/fphys.2015.00299 ISSN=1664-042X ABSTRACT=

The alkaline pH-activated, two-pore domain K⁺ channel K_2P5.1 (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 K_2P5.1 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 K_2P5.1 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 K_2P5.1 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 K_2P5.1 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 K_2P5.1 was higher in CD4⁺CD25⁻ T cells than in CD4⁺CD25⁺ regulatory T cells. The knockout of K_2P5.1 in mice significantly suppressed the disease responses implicated in the IBD model. Alternations in intracellular Ca²⁺ signaling following the dysregulated expression of K_2P5.1 were associated with the disease pathogenesis of IBD. The results of the present study suggest that the K_2P5.1 K⁺ channel in CD4⁺CD25⁻ T cell subset is a potential therapeutic target and biomarker for IBD.