Blockade of HERG K+ channel by isoquinoline alkaloid neferine in the stable transfected HEK293 cells

被引:45
作者
Gu, Dong-fang [2 ]
Li, Xue-lian [2 ]
Qi, Zhi-ping [2 ]
Shi, Sha-shan [2 ]
Hu, Mei-qin [2 ]
Liu, Dong-min [2 ]
She, Cheng-bai [2 ]
Lv, Yan-jie [2 ]
Li, Bao-xin [1 ,2 ]
Yang, Bao-feng [1 ,2 ]
机构
[1] Key Lab, Biopharmaceut Key Lab Heilongjiang Prov Incubator, Harbin 150081, Peoples R China
[2] Harbin Med Coll, Dept Pharmacol, Harbin 150081, Peoples R China
基金
中国国家自然科学基金;
关键词
Neferine; HEK293; cells; HERG channel; Patch clamp; Immunofluorescence; Western blot; LONG QT SYNDROME; POTASSIUM CHANNELS; PROTEIN TRAFFICKING; CARDIAC-ARRHYTHMIA; DE-POINTES; CURRENTS; PROLONGATION; INHIBITION; MECHANISM; DRUGS;
D O I
10.1007/s00210-009-0419-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We studied the effects of isoquinoline alkaloid neferine (Nef) extracted from the seed embryo of Nelumbo nucifera Gaertn on Human ether-a-go-go-related gene (HERG) channels stably expressed in human embryonic kidney (HEK293) cells using whole-cell patch clamp technique, western blot analysis and immunofluorescence experiment. Nef induced a concentration-dependent decrease in current amplitude according to the voltage steps and tail currents of HERG with an IC50 of 7.419 mu M (n(H)-0.5563). Nef shifted the activation curve in a significantly negative direction and accelerated recovery from inactivation and onset of inactivation, however, slowed deactivation. In addition, it had no significant influence on steady-state inactivation curve. Western blot and immunofluorescence results suggested Nef had no significant effect on the expression of HERG protein. In summary, Nef can block HERG K+ channels that functions by changing the channel activation and inactivation kinetics. Nef has no effect on the generation and trafficking of HERG protein. A blocked-off HERG channel was one mechanism of the anti-arrhythmic effects by Nef.
引用
收藏
页码:143 / 151
页数:9
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