Inhibition of Kv1.3 potassium current by phosphoinositides and stromal-derived factor-1α in Jurkat T cells

The activation of Kv1.3 potassium channel has obligatory roles in immune responses of T lymphocytes. Stromal cell-derived factor-1α (SDF-1α) binds to C-X-C chemokine receptor type 4, activates phosphoinositide 3-kinase, and plays essential roles in cell migration of T lymphocytes. In this study, the effects of phosphoinositides and SDF-1α on Kv1.3 current activity were examined in the Jurkat T cell line using whole cell patch-clamp techniques. The internal application of 10 μM phosphatidylinositol 4,5-bisphosphate (PIP 2 ) or 10 μM phosphatidylinositol-3,4,5-trisphosphate (PIP 3 ) significantly reduced Kv1.3 current, but that of 10 μM phosphatidylinositol-4-monophosphate (PIP) did not. The coapplication of 10 μg/ml anti-PIP 3 antibody with PIP 2 from the pipette did not change the reduction of Kv1.3 current by PIP 2 , but the coapplication of the antibody with PIP 3 eliminated the reduction. The heat-inactivated anti-PIP 3 antibody had no effect on PIP 3 -induced inhibition. These results suggest that PIP 2 per se can reduce Kv1.3 current as well as PIP 3 . External application of 1 μM Akt-kinase inhibitor VIII did not reverse the effect of intracellular PIP 3 . External application of 10 and 30 ng/ml SDF-1α significantly reduced Kv1.3 current. Internal application of anti-PIP 3 antibody reversed the SDF-1α-induced reduction. These results suggest that, in Jurkat T cells, PIP 2 , PIP 3 , and SDF-1α reduce Kv1.3 channel activity and that the reduction by SDF-1α may be mediated by the enhancement of PIP 3 production. These novel inhibitory effects of phosphoinositides and SDF-1α on Kv1.3 current may have a significant function as a downregulation mechanism of Kv1.3 activity for the maintenance of T lymphocyte activation in immune responses.