电离辐射通过激活 BK K(+) 通道诱导神经胶质瘤细胞迁移。

Ionizing radiation induces migration of glioblastoma cells by activating BK K(+) channels.

机构信息

Department of Pharmacology, Toxicology and Clinical Pharmacy, University of Tübingen, Germany.

出版信息

Radiother Oncol. 2011 Oct;101(1):122-6. doi: 10.1016/j.radonc.2011.05.069. Epub 2011 Jun 23.

DOI:10.1016/j.radonc.2011.05.069

PMID:21704404

Abstract

BACKGROUND AND PURPOSE

Glioblastoma cells express high levels of Ca(2+)-activated BK K(+) channels which have been proposed to be indispensable for glioblastoma proliferation and migration. Since migration of glioblastoma cells is reportedly stimulated by ionizing radiation (IR), we tested for an IR-induced increase in BK channel activity and its effect on cell migration.

MATERIALS AND METHODS

T98G and U87MG cells were X-ray-irradiated with 0-2 Gy, BK channel activity was assessed by patch-clamp recording, migration by trans-well migration assay, and activation of the Ca(2+)/calmodulin-dependent kinase II (CaMKII) by immunoblotting.

RESULTS

IR dose-dependently stimulated migration of glioblastoma cells which was sensitive to the BK channel inhibitor paxilline. Ca(2+)-permeabilization of T98G cells activated up to 350 BK channels per cells. Importantly, IR stimulated an increase in BK channel open probability but did not modify the total number of channels. Moreover, IR activated CaMKII in a paxilline-sensitive manner. Finally, inhibition of CaMKII by KN-93 abolished the IR-stimulated migration.

CONCLUSIONS

We conclude that IR stimulates BK channel activity which results in activation of CaMKII leading to enhanced glioblastoma cell migration.

摘要

背景与目的

脑胶质瘤细胞表达高水平的钙激活 BK K(+)通道，该通道被认为对脑胶质瘤的增殖和迁移是必不可少的。由于脑胶质瘤细胞的迁移据称受到电离辐射（IR）的刺激，我们测试了 IR 诱导的 BK 通道活性增加及其对细胞迁移的影响。

材料与方法

用 X 射线照射 T98G 和 U87MG 细胞，0-2Gy，通过膜片钳记录评估 BK 通道活性，通过 Trans-well 迁移测定评估迁移，通过免疫印迹评估 Ca(2+)/钙调蛋白依赖性激酶 II (CaMKII)的激活。

结果

IR 剂量依赖性地刺激脑胶质瘤细胞的迁移，该迁移对 BK 通道抑制剂 paxilline敏感。T98G 细胞的 Ca(2+)通透性使多达 350 个 BK 通道激活/细胞。重要的是，IR 刺激 BK 通道开放概率增加，但不改变通道总数。此外，IR 以 paxilline 敏感的方式激活 CaMKII。最后，CaMKII 的抑制物 KN-93 消除了 IR 刺激的迁移。