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纳秒级电脉冲通过电压门控 K、Ca 和 TRPM8 通道使 U87 神经胶质瘤细胞的跨膜电位去极化。

Nanosecond pulsed electric fields depolarize transmembrane potential via voltage-gated K, Ca and TRPM8 channels in U87 glioblastoma cells.

机构信息

Univ. Limoges, CNRS, XLIM, UMR 7252, F-87000 Limoges, France.

Univ. Limoges, CNRS, XLIM, UMR 7252, F-87000 Limoges, France; Bioelectronics Department, École des Mines de Saint-Étienne, Centre Microélectronique de Provence - Georges Charpak Campus, 880 route de Mimet, 13541 Gardanne, France.

出版信息

Biochim Biophys Acta Biomembr. 2017 Oct;1859(10):2040-2050. doi: 10.1016/j.bbamem.2017.07.004. Epub 2017 Jul 8.

DOI:10.1016/j.bbamem.2017.07.004
PMID:28693898
Abstract

Nanosecond pulsed electric fields (nsPEFs) have a variety of applications in the biomedical and biotechnology industries. Cancer treatment has been at the forefront of investigations thus far as nsPEFs permeabilize cellular and intracellular membranes leading to apoptosis and necrosis. nsPEFs may also influence ion channel gating and have the potential to modulate cell physiology without poration of the membrane. This phenomenon was explored using live cell imaging and a sensitive fluorescent probe of transmembrane voltage in the human glioblastoma cell line, U87 MG, known to express a number of voltage-gated ion channels. The specific ion channels involved in the nsPEF response were screened using a membrane potential imaging approach and a combination of pharmacological antagonists and ion substitutions. It was found that a single 10ns pulsed electric field of 34kV/cm depolarizes the transmembrane potential of cells by acting on specific voltage-sensitive ion channels; namely the voltage and Ca2 gated BK potassium channel, L- and T-type calcium channels, and the TRPM8 transient receptor potential channel.

摘要

纳秒脉冲电场(nsPEFs)在生物医药和生物技术领域有多种应用。迄今为止,癌症治疗一直是研究的前沿,因为 nsPEFs 使细胞膜和细胞内的膜通透性增加,导致细胞凋亡和坏死。nsPEFs 还可能影响离子通道的门控,并且有可能在不破坏细胞膜的情况下调节细胞生理。使用活细胞成像和跨膜电压的敏感荧光探针,在人神经胶质瘤细胞系 U87 MG 中探索了这种现象,该细胞系表达多种电压门控离子通道。使用膜电位成像方法和药理学拮抗剂和离子替代物的组合,筛选出参与 nsPEF 反应的特定离子通道。结果发现,作用于特定的电压敏感离子通道的单个 10ns 脉冲电场 34kV/cm 会使细胞膜的跨膜电位去极化;即电压和 Ca2 门控 BK 钾通道、L 和 T 型钙通道以及 TRPM8 瞬时受体电位通道。

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