Submitted on December 27, 2008
Revised on March 16, 2009
Accepted on March 16, 2009
Inhibition of Kv1.3 potassium current by phosphoinositides and stromal-derived factor-1
in Jurkat T cells
Yuichiro Matsushita1, Susumu Ohya1, Yoshiaki Suzuki1, Haruna Itoda1, Takuya Kimura1, Hisao Yamamura2, and Yuji Imaizumi1*
1 Nagoya City University, Graduate School of Pharmaceutical Sciences
2 Nagoya City University Graduate School of Medical Sciences
* To whom correspondence should be addressed. E-mail: yimaizum{at}phar.nagoya-cu.ac.jp.
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 (CXCR4), activates phosphoinositide 3-kinase(PI3 kinase) and plays essential roles in cell migration of T lymphocyte. In this study, effects of phosphoinositides and SDF-1 on Kv1.3 current activity were examined in 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 co-application 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 co-application of the antibody with PIP3 removed 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. This novel inhibitory effects of phosphoinositides and SDF-1 on Kv1.3 current may have significant functions as a down-regulation mechanism of Kv1.3 activity for the maintenance of T lymphocyte activation in immune responses.
