tram-34 and Diabetes-Mellitus--Type-1

Kv1.3 and IKCa1 potassium channels participate in the maintenance of calcium-influx during lymphocyte activation. Kv1.3 channels have a prominent role in specific T cell subsets, presenting a possible target for selective immunomodulation. We investigated the impact of Kv1.3 and IKCa1 channel inhibitors on calcium-influx characteristics in human T cells in type 1 diabetes mellitus. We isolated lymphocytes from 9 healthy and 9 type 1 diabetic individuals and measured the alteration of calcium-influx with flow cytometry in the Th1, Th2, CD4 and CD8 subsets after treatment of samples with specific channel inhibitors. Our results indicate an increased reactivity of type 1 diabetes lymphocytes, which is correlated to their increased sensitivity to Kv1.3 channel inhibition. However, the contribution of Kv1.3 channels to calcium flux is not exclusive for a specific lymphocyte subset as previous reports suggest, but is characteristic for each subset investigated. Therefore, the proposed inhibition of Kv1.3 channels as a novel therapeutic approach for the treatment of type 1 diabetes mellitus may have a major effect on overall lymphocyte function in this disease.

Topics: Adult; Calcium Signaling; CD4 Antigens; CD8 Antigens; Cells, Cultured; Diabetes Mellitus, Type 1; Humans; Intermediate-Conductance Calcium-Activated Potassium Channels; Kv1.3 Potassium Channel; Lymphocyte Activation; Male; Middle Aged; Pyrazoles; Scorpion Venoms; T-Lymphocyte Subsets; Th1 Cells; Th2 Cells