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伽马射线对电压门控钾通道 Kv10.1 功能表达的作用及其在放射生物学反应中的重要性。

Role of gamma radiation on functional expression of the voltage-gated potassium channel Kv10.1 and its importance in the radiobiological response.

机构信息

Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, C.U., Coyoacán, 04510, CDMX, Mexico; Cátedras CONACYT - Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, C.U, Coyoacán, 04510, CDMX, Mexico.

Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, C.U., Coyoacán, 04510, CDMX, Mexico.

出版信息

Appl Radiat Isot. 2022 Sep;187:110331. doi: 10.1016/j.apradiso.2022.110331. Epub 2022 Jun 16.

Abstract

Exposure of biological systems to a radiation absorbed dose produces early and late radiogenic responses, such as ion channel modulation, oxidative stress, cell migration enhancement, and metabolic changes that could impact the efficiency of radiotherapy. To understand how radiation modulates ion channels, we irradiated HEK cells stably expressing the human ether à-go-go potassium channel-1 with gamma photons in the dose range of 2-10 Gy (Co, 0.2 Gy/min) and measured ionic currents generated by the channel. The importance of the Kv10.1 modulation by gamma radiation was studied using cell proliferation. Results showed that a radiation-absorbed dose of 4 Gy significantly reduced the Kv10.1-evoked currents by depolarizing pulses between -100 mV and +50 mV. Additionally, the expression of Kv10.1 positively modulates HEK293 proliferation and, certainly, prevents the effect of gamma radiation on this phenomenon. Results allow concluding that the modulation of the functional expression of the Kv10.1 channel, induced by gamma radiation, leads to the expression of a radioresistant phenotype in Kv10.1 expressing cells.

摘要

生物系统暴露于辐射吸收剂量下会产生早期和晚期放射源性反应,例如离子通道调制、氧化应激、细胞迁移增强和代谢变化,这些变化可能会影响放射疗法的效率。为了了解辐射如何调节离子通道,我们用γ光子照射稳定表达人 ether à-go-go 钾通道-1 的 HEK 细胞,γ光子辐射剂量范围为 2-10 Gy(Co,0.2 Gy/min),并测量通道产生的离子电流。使用细胞增殖研究了 γ 辐射对 Kv10.1 的调制的重要性。结果表明,4 Gy 的辐射吸收剂量通过将 -100 mV 至 +50 mV 的去极化脉冲显著降低了 Kv10.1 诱发的电流。此外,Kv10.1 的表达正向调节 HEK293 的增殖,并且肯定可以防止 γ 辐射对这种现象的影响。结果表明,γ 辐射诱导的 Kv10.1 通道功能表达的调制导致 Kv10.1 表达细胞中表现出耐辐射表型。

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