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Regulation of Single-Channel Conductance of Voltage-Dependent Anion Channel by Mercuric Chloride in a Planar Lipid Bilayer.
The Journal of Membrane Biology ( IF 2.3 ) Pub Date : 2020-08-04 , DOI: 10.1007/s00232-020-00134-1
Chetan Malik 1 , Subhendu Ghosh 1
Affiliation  

The existence of mercury in various forms, e.g., elemental, organic, and inorganic has been known for decades. In any of these forms, it is poisonous to metabolism. In this, an investigation about the effect of the inorganic form of mercury, i.e., mercuric chloride (HgCl2) to the mitochondrial voltage-dependent anion channel (VDAC), has been done after isolation from the cardiac and brain tissues of Wistar rats. In vitro electrophysiology experiments were performed in Cardiolipin planar lipid bilayer membrane (BLM) to study the change in the conductance, selectivity, and gating charge of VDAC post HgCl2 treatment. A reduction in mean conductance of VDAC from 4.3 ± 0.18 to 1.66 ± 0.11 nS was observed. Further, the Gating charge calculated before (± 3.5) and after HgCl2 treatment (± 2.3) showed significant difference. Later, VDAC’s behavior was studied at different concentrations of HgCl2 ranging from 0.1 μM to 1 mM. The Inhibitory concentration (IC50) was calculated from the linear regression plot. The IC50 was found to be 488.1 μM. In the asymmetrical HgCl2 (5:1), a permeability ratio of cation to anion was found to be 4.2. It is interpreted that VDAC functioning is affected due to the application of 4 mM HgCl2 and a reduction in the conductance, gating charge, and permeability of VDAC was detected. The results provide clues to HgCl2-induced toxicity mediated through VDAC in the Cardiolipin BLM.

Graphic Abstract



中文翻译:

平面脂质双层中氯化汞对电压依赖性阴离子通道单通道电导的调节。

数十年来,人们已经知道以各种形式存在的汞,例如元素、有机和无机汞。在任何这些形式中,它对新陈代谢都是有毒的。在此,从 Wistar 大鼠的心脏和脑组织中分离出来的无机形式的汞,即氯化汞 (HgCl 2 ) 对线粒体电压依赖性阴离子通道 (VDAC) 的影响进行了研究。在心磷脂平面脂质双层膜 (BLM) 中进行体外电生理实验,以研究 HgCl 2后 VDAC 的电导、选择性和门控电荷的变化治疗。观察到 VDAC 的平均电导从 4.3 ± 0.18 降至 1.66 ± 0.11 nS。此外,在 HgCl 2处理之前 (± 3.5) 和之后(± 2.3)计算的门控电荷显示出显着差异。后来,VDAC 的行为在不同浓度的 HgCl 2 下进行了研究,范围从 0.1 μM 到 1 mM。抑制浓度 (IC 50 ) 由线性回归图计算。发现IC 50为488.1 μM。在不对称 HgCl 2 (5:1) 中,发现阳离子与阴离子的渗透率比为 4.2。据解释,由于应用了 4 mM HgCl 2,VDAC 功能受到影响并且检测到 VDAC 的电导、门控电荷和磁导率降低。结果提供了通过心磷脂 BLM 中的 VDAC 介导的HgCl 2诱导的毒性的线索。

图形摘要

更新日期:2020-08-04
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