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

Dong-fang Gu, Xue-lian Li, Zhi-ping Qi, Sha-shan Shi, Mei-qin Hu, Dong-min Liu, Cheng-bai She, Yan-jie Lv, Bao-xin Li, Bao-feng Yang

文献索引：Naunyn Schmiedebergs Arch. Pharmacol. 380(2) , 143-51, (2009)

全文：HTML全文

摘要

We studied the effects of isoquinoline alkaloid neferine (Nef) extracted from the seed embryo of Nelumbo nucifera Gaertn on Human ether-à-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 IC(50) of 7.419 microM (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.