18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels
18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels
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DOI：
10.1038/aps.2012.22
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发表时间：
2012-06-01
影响因子：
8.2
通讯作者：
Xia, Jia-hong
中科院分区：
文献类型：
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作者：
Du, Yi-mei;Xia, Cheng-kun;Xia, Jia-hong
目的：比较两种立体异构体形式的甘草次酸对Na+电流、HERG和Kv1.5通道电流不同组分的影响。方法：在爪蟾卵母细胞中表达野生型（WT）和长QT综合征3型（LQT-3）突变体Delta KPQ Nav1.5通道以及HERG和Kv1.5通道。此外，还使用了分离的人心房肌细胞。采用双微电极电压钳技术记录电压激活电流。结果：18p-甘草次酸（18 β - ga, 1-100 μ mol/L）的灌注对WT和Delta KPQ Nav1.5通道产生的峰值电流（I-Na,I-p）和后期电流（I-Na,I-L）均呈浓度依赖性阻断，而相同浓度的18 α -甘草次酸（18 α - ga）无影响。18 β - ga优先阻断由Delta KPQ Nav1.5通道产生的I-Na，I-L （IC50=37.2 +/- 14.4 mu mol/L）到I-Na，I-p （IC50=100.4 +/- 11.2 mu mol/L）。在人心房肌细胞中，18 β - ga （30 μ mol/L）抑制了由厌氧毒素（ATX-II, 30 nmol/L）诱导的47%的I-Na，I-P和87%的I-Na，I-L。18 β - ga （100 μ mol/L）对HERG和Kv1.5通道电流无影响。结论：18 β - ga优先阻断晚期Na电流，不影响HERG和Kv1.5通道。
Aim: To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na+ current, HERG and Kv1.5 channel currents.Methods: Wild-type (WT) and long QT syndrome type 3 (LQT-3) mutant Delta KPQ Nav1.5 channels, as well as HERG and Kv1.5 channels were expressed in Xenopus oocytes. In addition, isolated human atrial myocytes were used. Two-microelectrode voltage-clamp technique was used to record the voltage-activated currents.Results: Superfusion of 18p-glycyrrhetinic acid (18 beta-GA, 1-100 mu mol/L) blocked both the peak current (I-Na,I-p) and late current (I-Na,I-L) generated by WT and Delta KPQ Nav1.5 channels in a concentration-dependent manner, while 18 alpha-glycyrrhetinic acid (18 alpha-GA) at the same concentrations had no effects. 18 beta-GA preferentially blocked I-Na,I-L (IC50=37.2 +/- 14.4 mu mol/L) to I-Na,I-p (IC50=100.4 +/- 11.2 mu mol/L) generated by Delta KPQ Nav1.5 channels. In human atrial myocytes, 18 beta-GA (30 mu mol/L) inhibited 47% of I-Na,I-P and 87% of I-Na,I-L induced by Anemonia sulcata toxin (ATX-II, 30 nmol/L). Superfusion of 18 beta-GA (100 mu mol/L) had no effects on HERG and Kv1.5 channel currents.Conclusion: 18 beta-GA preferentially blocked the late Na current without affecting HERG and Kv1.5 channels.