18β-Glycyrrhetinic acid preferentially blocks late Na current generated by AKPQ Navl.5 channels

Aim： To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na current, HERG and Kvl.5 channel currents. Methods： Wild-type （WT） and long QT syndrome type 3 （LQT-3） mutant AKPQ Navl.5 channels, as well as HERG and Kvl.5 channels were expressed in Xenopus...

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Published in:中国药理学报：英文版 2012, Vol.33 (6), p.752-760
Main Author: Yi-mei DU Cheng-kun XIA Ning ZHAO Qian DONG Ming LEI Jia-hong XIA
Format: Article
Language:English
Subjects:
后期
浓度依赖性
渠道
爪蟾卵母细胞
甘草次酸
甘草酸
钠电流
长QT综合征
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Summary:Aim： To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na current, HERG and Kvl.5 channel currents. Methods： Wild-type （WT） and long QT syndrome type 3 （LQT-3） mutant AKPQ Navl.5 channels, as well as HERG and Kvl.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 1813-glycyrrhetinic acid （1813-GA, 1-100 pmol/L） blocked both the peak current （INa,P） and late current （INa,L） generated by WT and AKPQ Navl.5 channels in a concentration-dependent manner, while 18a-glycyrrhetinic acid （18a-GA） at the same concentrations had no effects. 1813-GA preferentially blocked INa,L （IC50=37-2＋14.4 pmol/L） to INa,P （IC5o=100.4＋11.2 IJmol/L） generated by AKPQ Navl.5 channels. In human atrial myocytes, 18β-GA （30 pmoVL） inhibited 47% of INa,P and 87% of INa,L induced by Anemonia sulcata toxin （ATX-II, 30 nmol/L）. Superfusion of 1813-GA （100 pmol/L） had no effects on HERG and Kvl.5 channel currents. Conclusion： 1813-GA preferentially blocked the late Na current without affecting HERG and Kvl.5 channels.
ISSN:1671-4083
1745-7254