Effect of dexamethasone on voltage-gated K+ channels in Jurkat T-lymphocytes.
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).
Lampert
Angelika
A
Physiologisches Institut, Universität Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
Müller
Matthias M
MM
Berchtold
Susanne
S
Lang
Karl S
KS
Palmada
Monica
M
Dobrovinskaya
Oxana
O
Lang
Florian
F
D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000172:deficiency / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000378:metabolism* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors*
D002121:Calcium Channel Blockers; D005938:Glucocorticoids; D024642:Potassium Channels, Voltage-Gated; D003907:Dexamethasone; D002118:Calcium