III类抗心律失常药RP58866对豚鼠及犬内向整流及瞬时外向钾电流的作用  

EFFECTS OF NOVEL CLASS III ANTIARRHYTHMIC DRUG RP58866 ON I K1 AND I to IN GUINEA PIG AND CANINE VENTRICULAR MYOCYTES

作　　者：杨宝峰[1] 孙建平[1] 李贵荣[2] StanleyNattel 周晋[1] 高焕焕[1] 

机构地区：[1]哈尔滨医科大学药理教研室,哈尔滨150086 [2]加拿大蒙特利尔心脏病研究所

出　　处：《药学学报》1999年第10期730-733,共4页Acta Pharmaceutica Sinica

摘　　要：目的：研究ＩＩＩ类抗心律失常药ＲＰ５８８６６ 对ＩＫ１ ，瞬时外向钾电流（Ｉｔｏ） 的作用。方法：用豚鼠和犬离体心肌细胞及全细胞电压钳技术。结果：在－ １００ ｍ Ｖ 时，ＲＰ５８８６６ 以浓度依赖方式明显减少了豚鼠心室肌细胞ＩＫ１ ，其ＩＣ５０ 为（３－４±０－８） μｍｏｌ·Ｌ－ １ 。在犬心室肌细胞，ＲＰ５８８６６ 可明显抑制Ｉｔｏ（ 在１００ μｍｏｌ·Ｌ－ １ 时减少８７％ ±２－１％ ），其ＩＣ５０ 为（２－３±０－５） μｍｏｌ·Ｌ－ １ 。结论：ＲＰ５８８６６ 对心肌细胞的ＩＫ１ 和Ｉｔｏ 均有抑制作用。AIM: Novel class III antiarrhythmic compounds RP58866 are known to block inward rectifier K + current ( I K1 ), and have been used as “specific” probes for the physiologic role of I K1 . However, the specificity is not completely established. The present study was designed to determine the effects of RP58866 on I K1 and transient outward K + current ( I to) in isolated cardia myocytes. METHODS: The tight seal cell clamp technique was used. RESULTS: RP58866 significantly decreased I K1 in a concentration dependent manner, with an IC 50 of (3 4±0 8) μmol·L -1 ( ±s ) at -100 mV in guinea pig ventricular cells. In canine ventricular myocytes, RP58866 significantly inhibited I to (decreased by 87%±2 1% at 100 μmol·L -1 ) with IC 50 an of (2 3±0 5) μmol·L -1 . CONCLUSION: Our results suggest that RP58866 inhibits I K1 and I to in cardiac myocytes with similar potency and that the compound is not a specific I K1 inhibitor.

关 键 词：离子通道 钾通道阻断剂 抗心律失常药 药理 

分 类 号：R972.2[医药卫生—药品]