Effects of Allicin on Late Sodium Current Caused by ΔKPQ-SCN5A Mutation in HEK293 Cells.
Effects of Allicin on Late Sodium Current Caused by ΔKPQ-SCN5A Mutation in HEK293 Cells.
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大蒜素对 HEK293 细胞中 αKPQ-SCN5A 突变引起的晚期钠电流的影响
DOI：
10.3389/fphys.2021.636485
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发表时间：
2021
影响因子：
4
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Chen Y;Huang Y;Bai J;Liu C;Ma S;Li J;Lu X;Fu Z;Fang L;Li Y;Zhang J
目的是研究大蒜素（Allicin）对HEK293细胞中ΔKPQ-SCN5A突变的晚钠电流异源表达的影响，以期筛选治疗长QT综合征3型（LQT3）的新药。通过脂质体技术将ΔKPQ-SCN5A质粒瞬时转入HEK293细胞中并通过细胞外灌注给药，并通过全细胞膜片钳技术记录钠电流。应用大蒜素 30 μM 将 ΔKPQ-SCN5A 编码的 Nav1.5 通道电流的晚期钠电流 (INa,L) 从 1.92 ± 0.12 降低至 0.65 ± 0.03 pA/pF (P < 0.01, n = 15)，从而导致 INa,L/INa,P 降低（从 0.94% ± 0.04%）至 0.32% ± 0.02%）。此外，大蒜素处理可使通道稳态失活向更负的方向移动，导致相同电压下通道失活增加，从而减少了窗口电流的增加，并进一步增加了通道中间态失活。然而，它对通道稳态激活（SSA）、失活机制和失活后的恢复动力学没有影响。此外，在 30 mM 大蒜素的作用下，ΔKPQ-SCN5A 突变的膜 Nav1.5 通道蛋白水平从 0.49% ± 0.04% 增强至 0.76% ± 0.02%，接近 WT 的 0.89% ± 0.02%。大蒜素降低了ΔKPQ-SCN5A的晚期钠电流，其机制可能与药物增加通道稳态失活（SSI）和中间态失活（ISI），从而降低窗口电流有关。
The aim was to study the effect of Allitridum (Allicin) on the heterologous expression of the late sodium current on the ΔKPQ-SCN5A mutations in HEK293 cells, with a view to screening new drugs for the treatment of long QT syndrome type 3 (LQT3). The ΔKPQ-SCN5A plasmid was transiently transferred into HEK293 cells by liposome technology and administered by extracellular perfusion, and the sodium current was recorded by whole-cell patch-clamp technology. Application of Allicin 30 μM reduced the late sodium current (INa,L) of the Nav1.5 channel current encoded by ΔKPQ-SCN5A from 1.92 ± 0.12 to 0.65 ± 0.03 pA/pF (P < 0.01, n = 15), which resulted in the decrease of INa,L/INa,P (from 0.94% ± 0.04% to 0.32% ± 0.02%). Furthermore, treatment with Allicin could move the steady-state inactivation of the channel to a more negative direction, resulting in an increase in channel inactivation at the same voltage, which reduced the increase in the window current and further increased the inactivation of the channel intermediate state. However, it had no effect on channel steady-state activation (SSA), inactivation mechanics, and recovery dynamics after inactivation. What’s more, the Nav1.5 channel protein levels of membrane in the ΔKPQ-SCN5A mutation were enhanced from 0.49% ± 0.04% to 0.76% ± 0.02% with the effect of 30 mM Allicin, close to 0.89% ± 0.02% of the WT. Allicin reduced the late sodium current of ΔKPQ-SCN5A, whose mechanism may be related to the increase of channel steady-state inactivation (SSI) and intermediate-state inactivation (ISI) by the drug, thus reducing the window current.
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DOI：
10.1161/circep.111.962019
发表时间：
2012-08-01
期刊：
Circulation. Arrhythmia and electrophysiology
影响因子：
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作者：
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DOI：
10.1111/j.1440-1681.2011.05511.x
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2011-05-01
影响因子：
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