Potassium ion (K
+) channels play an important role in the modulation of calcium ion (Ca
2+) signaling
via control of the membrane potential. In T-lymphocytes, the voltage-gated K
+ channel, K
V1.3, and the intermediate-conductance Ca
2+-activated K
+ channel, K
Ca3.1, predominantly contribute to K
+ conductance, and are responsible for cell proliferation, differentiation, apoptosis and infiltration. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, afflicts more than 0.1% of the population worldwide. In the chemically-induced IBD model mouse, an increase in K
Ca3.1 activity was observed in mesenteric lymph node CD4
+ T-lymphocytes, concomitant with an upregulation of K
Ca3.1 and a positive K
Ca3.1 regulator, NDPK-B. Pharmacological blockade of the K
Ca3.1 K
+ channel by TRAM-34 and/or ICA17043 elicited 1) a significant decrease in IBD severity, as assessed by diarrhea, visible fecal blood, inflammation and crypt damage of the colon; and 2) restoration of the expression levels of K
Ca3.1 and Th1 cytokines in CD4
+ T-lymphocytes in the IBD model. Recent studies have indicated the impact of K
2P5.1 upregulation in T lymphocytes on the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The K
2P5.1 K
+ channel is therefore highlighted as a potent therapeutic target in managing the pathogenesis of autoimmune diseases. Alternatively, pre-mRNA splicing of ion channels is associated with the development and progression of various diseases, including autoimmune diseases. Therefore, mRNA-splicing mechanisms underlying the transcriptional regulation of K
2P5.1 K
+ channels may be a new strategic therapeutic target for autoimmune and inflammatory diseases.
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