抗癫痫药物氨己烯酸（γ-乙烯基 GABA）对人神经胶质瘤细胞中中电导钙激活钾通道的抗抑郁作用。

Depressive effectiveness of vigabatrin (γ-vinyl-GABA), an antiepileptic drug, in intermediate-conductance calcium-activated potassium channels in human glioma cells.

机构信息

Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan.

Neuroscience Program, McGill University, Montréal, Quebec, Canada.

出版信息

BMC Pharmacol Toxicol. 2021 Jan 13;22(1):6. doi: 10.1186/s40360-021-00472-3.

BACKGROUND

Vigabatrin (VGB) is an approved non-traditional antiepileptic drug that has been revealed to have potential for treating brain tumors; however, its effect on ionic channels in glioma cells remains largely unclear.

METHODS

With the aid of patch-clamp technology, we investigated the effects of VGB on various ionic currents in the glioblastoma multiforme cell line 13-06-MG.

RESULTS

In cell-attached configuration, VGB concentration-dependently reduced the activity of intermediate-conductance Ca-activated K (IK) channels, while DCEBIO (5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) counteracted the VGB-induced inhibition of IK channels. However, the activity of neither large-conductance Ca-activated (BK) nor inwardly rectifying K (K) channels were affected by the presence of VGB in human 13-06-MG cells. However, in the continued presence of VGB, the addition of GAL-021 or BaCl effectively suppressed BK and K channels.

CONCLUSIONS

The inhibitory effect of VGB on IK channels demonstrated in the current study could be an important underlying mechanism of VGB-induced antineoplastic (e.g., anti-glioma) actions.

背景

氨己烯酸（VGB）是一种已被证实具有治疗脑肿瘤潜力的新型抗癫痫药物，但它对神经胶质瘤细胞离子通道的影响在很大程度上仍不清楚。

方法

借助膜片钳技术，我们研究了 VGB 对多形性成胶质细胞瘤细胞系 13-06-MG 中各种离子电流的影响。

结果

在细胞贴附式构型中，VGB 浓度依赖性地降低了中间电导钙激活钾（IK）通道的活性，而 DCEBIO（5,6-二氯-1-乙基-1,3-二氢-2H-苯并咪唑-2-酮）则拮抗了 VGB 对 IK 通道的抑制作用。然而，VGB 对人 13-06-MG 细胞中大电导钙激活（BK）和内向整流钾（K）通道的活性均无影响。然而，在持续存在 VGB 的情况下，添加 GAL-021 或 BaCl 可有效抑制 BK 和 K 通道。