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

The alkaline pH activated, two pore domain K+ channel K(2P)5.1 (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(2P)5.1 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(2P)5.1 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(2P)5.1 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(2P)5.1 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(2P)5.1 was higher in CD4(+)CD25(-) T cells than in CD4(+)CD25(+) regulatory T cells. The knockout of K(2P)5.1 in mice significantly suppressed the disease responses implicated in the IBD model. Alternations in intracellular Ca2+ signaling following the dysregulated expression of K(2P)5.1 were associated with the disease pathogenesis of IBD. The results of the present study suggest that the K(2P)5.1 K channel in CD4(+)CD25(-) T cell subset is a potential therapeutic target and biomarker for IBD.