The Novel Mechanism of Oxymatrine Affecting hERG Currents at Different Temperatures
The Novel Mechanism of Oxymatrine Affecting hERG Currents at Different Temperatures
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DOI：
10.1159/000322319
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
Yang, Bao-Feng
中科院分区：
文献类型：
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作者：
Hu, Mei-Qin;Dong, Zeng-Xiang;Yang, Bao-Feng
背景/目的：人ether-a-go-go-related基因（hERG）在心脏动作电位复极过程中起重要作用。本研究旨在探讨苦参素（Oxymatrine）在不同温度下对hERG编码的K+通道的作用及其机制。方法：采用全细胞膜片钳技术检测氧化苦参碱对HEK 293细胞hERG通道的影响。结果：在30 ℃时，氧化苦参碱呈浓度依赖性抑制hERG电流，IC 50约为665 μ M。但在20 ℃时，低浓度氧化苦参碱C（100 μ M）对hERG电流密度有明显的抑制作用。氧化苦参碱在所有温度下仅影响hERG通道的激活动力学，并且除了300 μ M-20 ℃组对hERG通道的失活状态具有高结合亲和力外，氧化苦参碱对hERG通道的开放状态具有高结合亲和力。结论：氧化苦参碱在30 ℃时是hERG K+通道的低效阻断剂，低浓度氧化苦参碱在20 ℃时影响hERG激活门控，加速hERG尾电流，氧化苦参碱在低温下是潜在的hERG激活剂。版权所有（C）2010 S. Karger AG，巴塞尔
Background/Aims: Human ether-a-go-go-related gene (hERG) has an important role in the repolarization of the cardiac action potential. Our studies were to investigate the effects of oxymatrine (one of the natural constituents extracted from Chinese herb Sophora flavescens Ait) on hERG-encoded K+ channels at different temperatures and its underlying mechanism. Methods: The effects of oxymatrine were examined on hERG channels stably expressed in HEK293 cells using a whole-cell patch clamp technique. Results: At the temperature 30 degrees C, oxymatrine inhibited hERG current in a concentration-dependent manner and the IC50 was similar to 665 mu M. However at the temperature of 20 degrees C, low concentration oxymatrine C 100 mu M inhibited the hERG current density significantly. Oxymatrine only affected the activation kinetic of hERG channels at all temperatures and had a high binding affinity for open state of hERG channels except the 300 mu M-20 degrees C group which had a high binding affinity for inactive state of hERG channels. Conclusion: Oxymatrine is a low potency blocker of hERG K+ channels at 30 degrees C, low concentration oxymatrine affect the hERG activation gating with accelerating hERG tail current at 20 degrees C, oxymatrine is a potential hERG activator at low temperatures. Copyright (C) 2010 S. Karger AG, Basel