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AB0047 The effects of KV1.3 and IKCA1 potassium channel inhibition on calcium influx of human peripheral T lymphocytes in rheumatoid arthritis
  1. G. Toldi1,
  2. A. Bajnok1,
  3. D. Dobi2,
  4. A. Kaposi1,
  5. L. Kovács2,
  6. B. Vásárhelyi3,
  7. A. Balog2
  1. 1First Dept of Pediatrics, Semmelweis University, Budapest
  2. 2Dept of Rheumatology, University of Szeged, Szeged
  3. 3Dept of Laboratory Medicine, Semmelweis University, Budapest, Hungary

Abstract

Background The transient increase of the cytoplasmic free calcium level plays a key role in the process of lymphocyte activation. Kv1.3 and IKCa1 potassium channels are important regulators of the maintenance of calcium influx during lymphocyte activation and present a possible target for selective immunomodulation.

Objectives We aimed to characterize the effects of lymphocyte potassium channel inhibition on peripheral blood T lymphocyte activation in rheumatoid arthritis (RA).

Methods We took peripheral blood samples from 10 healthy individuals and 9 recently diagnosed RA patients receiving no anti-rheumatic treatment. We evaluated calcium influx kinetics following activation in CD4, Th1, Th2 and CD8 cells applying a novel flow cytometry approach. We also assessed the sensitivity of the above subsets to specific inhibition of the Kv1.3 and IKCa1 potassium channels.

Results The peak of calcium influx in lymphocytes isolated from RA patients is reached more rapidly, indicating that they respond more quickly to stimulation compared to controls. In healthy individuals, the inhibition of the IKCa1 channel decreased calcium influx in Th2 and CD4 cells to a lower extent than in Th1 and CD8 cells. On the contrary, the inhibition of Kv1.3 channels resulted in a larger decrease of calcium entry in Th2 and CD4 than in Th1 and CD8 cells. No difference was detected between Th1 and Th2 or CD4 and CD8 cells in the sensitivity to IKCa1 channel inhibition among lymphocytes of RA patients. However, specific inhibition of the Kv1.3 channel acts differentially on calcium influx kinetics in RA lymphocyte subsets. Th2 and particularly CD8 cells are inhibited more dominantly than Th1 and CD4 cells.

Conclusions Inhibition of Kv1.3 channels does not seem to be specific enough in peripheral RA lymphocytes, since anti-inflammatory Th2 cells are also affected to a noteworthy extent. Further studies are needed to evaluate the therapeutic potential of lymphocyte potassium channel inhibition in RA.

Disclosure of Interest None Declared

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