Modulation of T Lymphocyte Calcium Influx Patterns Via the Inhibition of Kv1.3 and Ikca1 Potassium Channels in Autoimmune Disorders

cells play a pivotal role in the pathogenesis of autoimmunity (4). Wulff et al. described that the characteristic potassium channel phenotype of TEM cells in multiple sclerosis (MS) is Kv1.3high IKCa1low, contrasting naïve, and central memory T (TCM) cells, which exhibit a Kv1.3low IKCa1high channel phenotype (1). Therefore the therapeutic relevance of specific Kv1.3 channel inhibitors is of outstanding interest, as they may offer the possibility for selective modulation of pathogenic TEM cells, while naïve and TCM cells (needed for physiological immune responses) would escape the inhibition through upregulation of IKCa1 channel expression. Beeton et al. demonstrated that the symptoms of experimental autoimmune encephalitis, a murine model of MS, significantly improved after treatment with selective Kv1.3 inhibitors (5). Although results from animal models are promising, limited data is available on the effects of potassium channel inhibition on T cell function in humans. Furthermore, besides naïve and memory T cells, alterations in the activation pattern of effector (CD4+ helper and CD8+ cytotoxic) T lymphocytes have not been described upon Kv1.3 and IKCa1 inhibition. Although these cells might have a less-specific role in the maintenance of autoreactivity compared to TEM cells, their inhibition have important consequences on the overall immune response. Therefore, over the recent years, we have investigated calcium influx characteristics in effector T cell subsets in a number of autoimmune disorders. We isolated peripheral blood mononuclear cells from MS, rheumatoid arthritis (RA) and type 1 diabetes mellitus (T1DM) patients and applied a novel flow cytometry-based approach for the detection of calcium influx (7–10). Until the recent Modulation of T lymphocyte calcium influx patterns via the inhibition of Kv1.3 and IKCa1 potassium channels in autoimmune disorders