Abstract
The voltage-gated K+ channel Kv1.3 is an important regulator of lymphocyte function. Activation of lymphocytes is accompanied by stimulation, whereas CD95-induced apoptosis by inhibition, of Kv1.3. The channel serves to maintain cell membrane potential, a prerequisite for signalling through the Ca2+ release-activated Ca2+ channel ICRAC. As glucocorticoids are known to regulate lymphocyte function, the present study addressed the effect of dexamethasone on voltage-gated K+ channels in Jurkat T-lymphocytes. In whole-cell patch-clamp experiments current families evoked by 200-ms potential steps every 15 s from −70 mV to values from −120 to +100 mV revealed the functional expression of voltage-gated K+ channels. Pre-treatment of Jurkat T-lymphocytes for 2–3 h with 1 µM dexamethasone led to a significant decrease of voltage-gated K+ currents. Fura-2-fluorescence measurements showed that the readdition of Ca2+ to Ca2+-depleted cells led to a rapid increase of cytosolic Ca2+ activity. This increase of Ca2+ activity was blunted by both the K+ channel blocker margatoxin (10 nM) and 24 h pre-treatment with dexamethasone (1 µM). In conclusion, dexamethasone inhibits voltage-gated K+ channels in Jurkat T-lymphocytes, an effect impeding Ca2+ entry through ICRAC.
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Acknowledgements
The authors gratefully acknowledge the technical assistance of E. Faber. This work was supported by the Deutsche Forschungsgemeinschaft (La 315/4-4, Le 792/3-3), a grant of the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (Fö. 01KS9602) and the Interdisziplinäres Zentrum für Klinische Forschung der Universität Tübingen (IZKF) (S. 05.00023.2/IIB9) and of the fortune program, Tübingen.
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Lampert, A., Müller, M.M., Berchtold, S. et al. Effect of dexamethasone on voltage-gated K+ channels in Jurkat T-lymphocytes. Pflugers Arch - Eur J Physiol 447, 168–174 (2003). https://doi.org/10.1007/s00424-003-1148-2
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DOI: https://doi.org/10.1007/s00424-003-1148-2