The intermediate-conductance Ca2+-activated K+ channel KCa3.1/KCNN4 plays an important role in the modulation of Ca2+ signaling through the control of the membrane potential in T lymphocytes. Here, we study the involvement of KCa3.1 in the enlargement of the mesenteric lymph nodes (MLNs in a mouse model of inflammatory bowel disease (IBD. The mouse model of IBD was prepared by exposing male C57BL/6J mice to 5% dextran sulfate sodium for 7 days. Inflammation-induced changes in KCa3.1 activity and the expressions of KCa3.1 and its regulators in MLN CD4+ T lymphocytes were monitored by real-time PCR, Western blot, voltage-sensitive dye imaging, patch-clamp, and flow cytometric analyses. Concomitant with an upregulation of KCa3.1a and nucleoside diphosphate kinase B (NDPK-B, a positive KCa3.1 regulator, an increase in KCa3.1 activity was observed in MLN CD4+ T lymphocytes in the IBD model. Pharmacological blockade of KCa3.1 elicited the following results: 1 a significant decrease in IBD disease severity, as assessed by diarrhea, visible fecal blood, inflammation, and crypt damage of the colon and MLN enlargement compared with control mice, and 2 the restoration of the expression levels of KCa3.1a, NDPK-B, and Th1 cytokines in IBD model MLN CD4+ T lymphocytes. These findings suggest that the increase in KCa3.1 activity induced by the upregulation of KCa3.1a and NDPK-B may be involved in the pathogenesis of IBD by mediating the enhancement of the proliferative response in MLN CD4+ T lymphocyte and, therefore, that the pharmacological blockade of KCa3.1 may decrease the risk of IBD.
|Journal||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|Publication status||Published - 15-05-2014|
All Science Journal Classification (ASJC) codes
- Physiology (medical)