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

来源：

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY | 2009年 / 380卷 / 02期

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

页码：143 / 151

页数：9

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