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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(Istep)及其尾电流(Itail)。在0 mV时,10、30、100及300μmol.L-1槐果碱对Istep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Itail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)。100μmol.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。
The potassium channel of HERG (human ether-a-go-go-related gene) plays an important role in the occurrence and treatment of arrhythmia, so it has become a research hotspot in recent years. In this study, the current and kinetic curves (activated, inactivated, revived, and deactivated) of HERG potassium channels stably expressed on HEK (human embryonic kidney) 293 cells were recorded using a whole cell patch clamp technique to investigate the effects of different concentrations of sarcothene. The influence of HERG current and kinetic curves to understand the mechanism of anti-arrhythmic effects of sophocarpine. The results indicate that sarcoma inhibits the HERG time-dependent current (Istep) and its tail current (Itail) in a concentration-dependent manner. At 0 mV, the inhibitory rates of 10, 30, 100, and 300 μmol·L-1 sophocarpine on Istep were (10.7±2.8)%, (11.3±5.5)%, (47.0±2.3)%, and (53.7±) respectively. In 2.5)%, the inhibition rates to Itail were (1.1±3.0)%, (17.1±3.3)%, (32.7±1.9)% (P<0.05, n=12) and (56.0±2.4)%, respectively (P< 0.05, n=13). After 100μmol.L-1 sophocarpine treatment, the inactivation time constant decreased and the inactivation rate became faster. The resurrection time constant decreased significantly under most commanded voltages (P<0.01, n=12), and the recovery rate accelerated. The inactivation time constant decreased (P<0.05, n=12); steady state activation and deactivation did not change significantly. It can be seen that sophocarpine inhibits the HERG potassium current by influencing the inactivation process of the channel, so that the repolarization time of the myocardium is prolonged and the rapid arrhythmia is improved.