Inhibition of Kv1.3 potassium current by phosphoinositides and stromal-derived factor-1alpha in Jurkat T cells.
Inhibition of Kv1.3 potassium current by phosphoinositides and stromal-derived factor-1alpha in Jurkat T cells.
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DOI：
10.1152/ajpcell.00668.2008
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
Y. Matsushita;S. Ohya;Yoshiaki Suzuki;Haruna Itoda;Takuya Kimura;H. Yamamura;Y. Imaizumi
中科院分区：
文献类型：
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作者：
Y. Matsushita;S. Ohya;Yoshiaki Suzuki;Haruna Itoda;Takuya Kimura;H. Yamamura;Y. Imaizumi
Kv1.3 钾通道的激活在 T 淋巴细胞的免疫反应中具有重要作用。基质细胞衍生因子 1α (SDF-1α) 与 4 型 C-X-C 趋化因子受体结合，激活磷酸肌醇 3-激酶，并在 T 淋巴细胞的细胞迁移中发挥重要作用。在本研究中，使用全细胞膜片钳技术在 Jurkat T 细胞系中检查了磷酸肌醇和 SDF-1α 对 Kv1.3 电流活性的影响。内服10μM磷脂酰肌醇4,5-二磷酸(PIP(2))或10μM磷脂酰肌醇-3,4,5-三磷酸(PIP(3))显着降低Kv1.3电流，但10μM磷脂酰肌醇-4-单磷酸(PIP)则没有显着降低Kv1.3电流。将10μg/ml抗PIP(3)抗体与移液器中的PIP(2)共同应用并没有改变PIP(2)对Kv1.3电流的减少，但该抗体与PIP(3)共同应用消除了这种减少。热灭活的抗 PIP(3) 抗体对 PIP(3) 诱导的抑制没有影响。这些结果表明 PIP(2) 本身可以像 PIP(3) 一样降低 Kv1.3 电流。外用1μM Akt激酶抑制剂VIII并不能逆转细胞内PIP的作用(3)。外用10和30 ng/ml SDF-1alpha可显着降低Kv1.3电流。内部应用抗PIP(3)抗体逆转了SDF-1α诱导的减少。这些结果表明，在 Jurkat T 细胞中，PIP(2)、PIP(3) 和 SDF-1α 降低 Kv1.3 通道活性，并且 SDF-1α 的降低可能是通过 PIP(3) 产生的增强介导的。磷酸肌醇和 SDF-1α 对 Kv1.3 电流的这些新的抑制作用可能作为 Kv1.3 活性的下调机制在维持免疫反应中 T 淋巴细胞活化方面具有重要作用。
The activation of Kv1.3 potassium channel has obligatory roles in immune responses of T lymphocytes. Stromal cell-derived factor-1alpha (SDF-1alpha) 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-1alpha on Kv1.3 current activity were examined in the Jurkat T cell line using whole cell patch-clamp techniques. The internal application of 10 microM phosphatidylinositol 4,5-bisphosphate (PIP(2)) or 10 microM phosphatidylinositol-3,4,5-trisphosphate (PIP(3)) significantly reduced Kv1.3 current, but that of 10 microM phosphatidylinositol-4-monophosphate (PIP) did not. The coapplication of 10 microg/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 muM Akt-kinase inhibitor VIII did not reverse the effect of intracellular PIP(3). External application of 10 and 30 ng/ml SDF-1alpha significantly reduced Kv1.3 current. Internal application of anti-PIP(3) antibody reversed the SDF-1alpha-induced reduction. These results suggest that, in Jurkat T cells, PIP(2), PIP(3), and SDF-1alpha reduce Kv1.3 channel activity and that the reduction by SDF-1alpha may be mediated by the enhancement of PIP(3) production. These novel inhibitory effects of phosphoinositides and SDF-1alpha 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.