Effect of dexamethasone on voltage-gated K+ channels in Jurkat T-lymphocytes

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 I(CRAC). 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 microM dexamethasone led to a significant decrease of voltage-gated K+ currents. Fura-2-fluorescence measurements showed that the readdition of Ca2+ to Ca(2+)-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 microM). In conclusion, dexamethasone inhibits voltage-gated K+ channels in Jurkat T-lymphocytes, an effect impeding Ca2+ entry through I(CRAC).