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Front Physiol. 2015 Oct 27;6:299. doi: 10.3389/fphys.2015.00299. eCollection 2015.

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.

Author information

1
Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Kyoto, Japan.
2
Institute of Resource Development and Analysis, Kumamoto University Kumamoto, Japan.

Abstract

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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.

KEYWORDS:

CD4+ T cell; Ca2+ influx; K2P5.1; background K+ channel; cytokine production; inflammatory bowel disease

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