Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K(+) Current and Intermediate-Conductance Ca(2+)-Activated K(+) Channel in Jurkat T-Lymphocytes

FTY720 (fingolimod), a modulator of sphingosine-1-phosphate receptors, is known to produce the immunomodulatory actions and to be beneficial for treating the relapsing multiple sclerosis. However, whether it exerts any effects on membrane ion currents in immune cells remains largely unknown. Herein, the effects of FTY720 on ionic currents in Jurkat T-lymphocytes were investigated. Cell exposure to FTY720 suppressed the amplitude of delayed-rectifier K(+) current (I(K(DR))) in a time- and concentration-dependent manner with an IC(50) value of 1.51 μM. Increasing the FTY720 concentration not only decreased the I(K(DR)) amplitude but also accelerated the inactivation time course of the current. By using the minimal reaction scheme, the effect of FTY720 on I(K(DR)) inactivation was estimated with a dissociation constant of 3.14 μM. FTY720 also shifted the inactivation curve of I(K(DR)) to a hyperpolarized potential with no change in the slope factor, and recovery from I(K(DR)) became slow during the exposure to this compound. Cumulative inactivation for I(K(DR)) in response to repetitive depolarizations was enhanced in the presence of FTY720. In SEW2871-treated cells, FTY720-induced inhibition of I(K(DR)) was attenuated. This compound also exerted a stimulatory action on the activity of intermediate-conductance Ca(2+)-activated K(+) channels in Jurkat T-lymphocytes. However, in NSC-34 neuronal cells, FTY720 did not modify the inactivation kinetics of KV3.1-encoded I(K(DR)), although it suppressed I(K(DR)) amplitude in these cells. Collectively, the perturbations by FTY720 on different types of K(+) channels may contribute to the functional activities of immune cells, if similar findings appear in vivo.