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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

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

Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Submitted 26 December 2008 ; accepted in final form 16 March 2009

The activation of Kv1.3 potassium channel has obligatory roles in immune responses of T lymphocytes. Stromal cell-derived factor-1 (SDF-1) 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-1 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 (PIP₂) or 10 µM phosphatidylinositol-3,4,5-trisphosphate (PIP₃) significantly reduced Kv1.3 current, but that of 10 µM phosphatidylinositol-4-monophosphate (PIP) did not. The coapplication of 10 µg/ml anti-PIP₃ antibody with PIP₂ from the pipette did not change the reduction of Kv1.3 current by PIP₂, but the coapplication of the antibody with PIP₃ eliminated the reduction. The heat-inactivated anti-PIP₃ antibody had no effect on PIP₃-induced inhibition. These results suggest that PIP₂ per se can reduce Kv1.3 current as well as PIP₃. External application of 1 µM Akt-kinase inhibitor VIII did not reverse the effect of intracellular PIP₃. External application of 10 and 30 ng/ml SDF-1 significantly reduced Kv1.3 current. Internal application of anti-PIP₃ antibody reversed the SDF-1-induced reduction. These results suggest that, in Jurkat T cells, PIP₂, PIP₃, and SDF-1 reduce Kv1.3 channel activity and that the reduction by SDF-1 may be mediated by the enhancement of PIP₃ production. These novel inhibitory effects of phosphoinositides and SDF-1 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.

potassium channel; T lymphocytes