乌头碱阻断表达在非洲爪蟾卵母细胞上人类kv1.5和herg钾通道-aconitine blocks human kv 1.5 and herg potassium channels expressed on xenopus laevis oocyte.docxVIP

华 中 科 技 大 学 博 士 学 位 论 文 4 while I508A,and V512A mutation increased the IC50 1199-fold (IC50=954.671±55.135μM), and 1150-fold (IC50=915.840±213.953μM) respectively.. Conclusions :In this study, we first find that aconitine blocks HERG and hKv1.5 channel expressed in Xenopus laevis oocytes in a voltage-and time- and concentrate –dependent manner .In addition, the feature of its blockage is consistent with the open-state channel blocker. Furthermore, aconitine blocks HERG channels as potent as E-4031 which is a typical and selective blocker of HERG channels, on the other hand , it blocks hKv1.5 channel as potent as the specific blockers of hKv1.5 channels such as DPO- 1、S0100176 and mor e pot ent t han AVE0118, t he ot her sel ect i ve bl ocker of hKv1. 5 channel s. These r esul t s suggest t hat blockage of potassium channels, particular HERG channel may be one of important mechanisms of arrhythmias indced by ACO. The mutations of HERG and hKv1.5 channel can result in decrease of block potency for aconitine. Y－652 may be the key binding site of ACO interacting with HERG channel, on the other hand ,V505，I508 and V512 may be the key binding site for Kv1.5 channel. . Key words: electrophysiology; aconitine; HERG potassium channel, Kv1.5 potassium channel; arrhythmias; voltage clamp techniques 58 缩略词表 英文缩写 ACO英文全称 Aconitine中文全称 乌头碱IkurUltrarapid Component of the delayed HERGrectifier potassium current Human ether-a-go-go-related gene超速激活的延迟整流钾电流 人类ether-a-go-go相关基因HKv1.5Human voltage-gated potassium人类 Kv1.5 钾通道channel 1.5IkrRapid Component of the delayedrectifier potassium current快激活的延迟整流钾电流IksSlow Component of the delayedrectifier potassium current慢激活的延迟整流钾电流 LQTSLong QT interval syndrome长 QT 综合征TdpTorsades de pointes尖端扭转型室性心动过速Y652ATyr-652-Ala652 位点酪氨酸突变为丙氨酸T480AThr-480-Ala480位点苏氨酸突变为丙氨酸V505AVal-505-Ala505位点缬氨酸突变为丙氨酸L506ALeu-506-Ala506位点亮氨酸突变为丙氨酸I508AIle-508-Ala508位点异亮氨酸突变为丙氨酸V512A V51