槐果碱对HERG钾通道电生理功能的影响

HERG(human ether-a-go-go-related gene)钾通道在心律失常的发生及治疗中具有重要作用， 因此已成为近些年来的研究热点。本研究应用全细胞膜片钳技术记录在HEK(human embryonic kidney) 293细胞上稳定表达的HERG钾通道的电流和动力学曲线(激活、 失活、 复活和去活化)来研究不同浓度槐果碱对HERG电流及动力学曲线的影响， 以了解槐果碱抗心律失常的作用机制。结果表明， 槐果碱浓度依赖性地抑制HERG时间依赖性电流(I_step)及其尾电流(I_tail)。在0 mV时， 10、 30、 100及300 μmol·L^-1槐果碱对I_step的抑制率分别为(10.7±2.8)%、 (11.3±5.5)%、 (47.0±2.3)%及(53.7±2.5)%， 对I_tail的抑制率分别为(1.1±3.0)%、 (17.1±3.3)%、 (32.7±1.9)%(P<0.05， n=12)及(56.0±2.4)%(P<0.05， n=13)。100 μmol·L^-1槐果碱作用后失活时间常数减小， 失活速率变快；复活时间常数在大部分指令电压下明显减小(P<0.01， n=12)，复活速度加快；瞬时失活时间常数减小(P<0.05， n=12)；稳态激活、去活化无明显改变。由此可看出，槐果碱通过影响通道的失活过程抑制HERG钾电流，使得心肌细胞复极时间延长，改善快速性心律失常。

Effect of sophocarpine on HERG K+ channels

Human ether-a-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier K+ current, which has an important effect on both proarrhythmia and antiarrhythmia. To investigate the effect of sophocarpine (SC) on HERG channel stably expressing in human embryonic kidney-293 (HEK293) cells, whole-cell patch-clamp technique was used to record HERG current and kinetic curves. As the result, it was found that SC inhibited HERG current in a concentration-dependent manner (10, 30, 100, and 300 micromol x L(-1)). At 0 mV, 10, 30, 100, and 300 micromol x L(-1) SC respectively inhibited IHERG by Istep ( 10.7 +/- 2.8)% , (11.3 +/- 5.5)% , (47.0 +/- 2.3)% and (53.7 +/- 2.5)% , and Itail (1.1 +/- 3.0)%, (17.1 +/- 3.3)%, (32.7 +/- 1.9)% (P < 0.05, n = 12) and (56.0 +/- 2.4)% (P < 0.05, n = 13). The time constants of inactivation, recovery from inactivation and onset of inactivation were accelerated. SC did not change other channel kinetics (activation and deactivation). It is concluded that SC inhibited the transfected HERG channels by influencing the inactivation state, which is the probable anti-arrhythmic mechanism.