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3-甲基菲对异源表达系统CHO-K1中由K11.1和Na1.5通道介导的离子电流的影响

The Effects of 3-Methylphenanthrene on Ion Currents Mediated by K11.1 and Na1.5 Channels in the Heterologous Expression System CHO-K1.

作者信息

Dzhumaniiazova I, Pustovit O B, Abramochkin D V

机构信息

Department of Human and Animal Physiology, Lomonosov Moscow State University, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2025 Apr;178(6):788-793. doi: 10.1007/s10517-025-06418-7. Epub 2025 May 30.

Abstract

Polycyclic aromatic hydrocarbons are widespread environmental pollutants that can accumulate in tissues and affect numerous physiological functions. Using the patch-clamp technique, we characterized the effects of an aromatic hydrocarbon 3-methylphenanthrene (3-MP) on currents mediated by the α-subunits of Na1.5 (I) and K11.1 (I) channels in the CHO-K1 heterologous expression system. 3-MP caused a dose-dependent blockade of I tail current (IC = 38.2 μM). At a concentration of 10 μM, 3-MP induced a shift in the half-activation potential (V) from -46.5 to -51.3 mV and reduced the time required for 50% of channels to become available from 120.9 to 99.6 msec. Significant changes were observed in inactivation parameters (V increased from -79.9 to -73.4 mV) and deactivation kinetics (time constant decreased from 63.5 to 46.3 msec). In contrast, I remained tolerant to the effects of 3-MP. Therefore, it can be assumed that 3-MP can lead to lengthening of the action potential in human working cardiomyocytes, without significantly altering its amplitude or the rate of its propagation.

摘要

多环芳烃是广泛存在的环境污染物,可在组织中蓄积并影响多种生理功能。我们采用膜片钳技术,在CHO-K1异源表达系统中,研究了芳烃3-甲基菲(3-MP)对由Na1.5(I)和K11.1(I)通道α亚基介导的电流的影响。3-MP对I尾电流产生剂量依赖性阻断(IC = 38.2 μM)。在10 μM浓度下,3-MP使半激活电位(V)从-46.5 mV移至-51.3 mV,并将50%通道可用所需时间从120.9毫秒缩短至99.6毫秒。失活参数(V从-79.9 mV升至-73.4 mV)和去激活动力学(时间常数从63.5毫秒降至46.3毫秒)均发生显著变化。相比之下,I对3-MP的作用具有耐受性。因此,可以推测3-MP可导致人类工作心肌细胞动作电位延长,而不会显著改变其幅度或传播速率。

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