Lymphocyte activation in type 1 diabetes mellitus: the increased significance of Kv1.3 potassium channels.
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.
Toldi
Gergely
G
First Department of Pediatrics, Semmelweis University, Budapest H-1083, Hungary. toldigergely@yahoo.com
Vásárhelyi
Barna
B
Kaposi
Ambrus
A
Mészáros
Gergo
G
Pánczél
Pál
P
Hosszufalusi
Nóra
N
Tulassay
Tivadar
T
Treszl
András
A
D000328:Adult; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D015704:CD4 Antigens; D016827:CD8 Antigens; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D051664:Kv1.3 Potassium Channel; D011720:Pyrazoles; D012604:Scorpion Venoms; C411671:TRAM 34; C077910:margatoxin