Different calcium influx characteristics upon Kv1.3 and IKCa1 potassium channel inhibition in T helper subsets.
Functional imbalance between T helper subsets plays important role in the pathogenesis of autoimmune disorders. Transient increase of cytoplasmic calcium level, and sustention of negative membrane potential by voltage sensitive Kv1.3 and calcium-dependent IKCa1 potassium channels are essential for short-term lymphocyte activation, thus present possible target for selective immunomodulation. We aimed to investigate calcium influx sensitivity to the inhibition of potassium channels in the main T helper subsets. Peripheral blood from 11 healthy individuals was drawn and calcium influx kinetics following activation with phytohemagglutinin in Th1, Th2, Th17, and Treg cells were evaluated. Alteration of calcium influx induced by specific inhibitors of Kv1.3 and IKCa1 potassium channels, and the expression of Kv1.3 channels were also assessed. Highest cytoplasmic calcium concentration was observed in stimulated Th1 cells, while the lowest level was measured in Treg cells. In Th1 and Th17 cells, inhibition of both investigated potassium channels decreased calcium influx. In Th2 cells only the inhibitor of Kv1.3 channels, while in Treg cells none of the inhibitors had significant effect. Upon the inhibition of IKCa1 channels, short-term activation of proinflammatory cells was specifically decreased without affecting anti-inflammatory subsets, indicating that selective immunomodulation is possible in healthy individuals.
First Department of Pediatrics, Semmelweis University, H-1083, Budapest, Hungary.
Csaba
C
Orbán
Anna
A
Bajnok
Barna
B
Vásárhelyi
Tivadar
T
Tulassay
Gergely
G
Toldi
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology*; D005260:Female; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors*; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D000911:Antibodies, Monoclonal; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D051664:Kv1.3 Potassium Channel; D010835:Phytohemagglutinins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011720:Pyrazoles; D012604:Scorpion Venoms; C411671:TRAM 34; C077910:margatoxin; D002118:Calcium
Th17; Treg; lymphocyte activation; potassium channels