Cellular Physiology and Biochemistry | |
The Novel Mechanism of Oxymatrine Affecting hERG Currents at Different Temperatures | |
关键词: HEK293 cell; hERG channel; Patch clamp; Oxymatrine; Temperature; | |
DOI : 10.1159/000322319 | |
学科分类:分子生物学,细胞生物学和基因 | |
来源: S Karger AG | |
【 摘 要 】
Background/Aims Human ether-à-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°C, oxymatrine inhibited hERG current in a concentration-dependent manner and the IC50 was ∼665 µM. However at the temperature of 20°C, low concentration oxymatrine C≤100 µM increased hERG current density. However, high concentration oxymatrine C>100 µM 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 µM-20°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°C, low concentration oxymatrine affect the hERG activation gating with accelerating hERG tail current at 20°C, oxymatrine is a potential hERG activator at low temperatures.
【 授权许可】
CC BY-NC-ND
【 预 览 】
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RO201901231005929ZK.pdf | 717KB | download |