盐酸昌欣沙星抑制开放状态的HERG钾通道  

Chinfloxacin hydrochloride inhibits HERG potassium channel at open state

作　　者：张香梅[1] 朱中华[1] 孙晓莉[1] 郭佳[1] 赵钟钟[1,2] 张朝[1,2] 

机构地区：[1]南京师范大学生命科学学院江苏省分子医学生物技术重点实验室,江苏南京210046 [2]南京师范大学生命科学学院江苏省超分了医用材料及应用重点实验室,江苏南京210046

出　　处：《药学学报》2010年第12期1491-1496,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30570662,30871228)

摘　　要：探讨一种新型氟喹诺酮类抗菌剂盐酸昌欣沙星(chinfloxacin hydrochloride,CFX)对HERG(human ether-à-go-go-related gene)钾离子通道动力学的影响。利用全细胞膜片钳技术,在HEK293细胞中记录异源表达的HERG钾电流,观察CFX对通道的抑制作用,分析其对通道激活、失活和去激活等动力学过程的影响。结果表明,CFX作用于HERG钾离子通道的开放状态,以浓度依赖的方式抑制HERG钾电流,半有效抑制浓度(IC50)为(162.1±14.2)μmol.L?1,是其改造前体盐酸莫西沙星的2倍,但CFX不改变通道动力学特性。由于改变细胞外液K+浓度,CFX对HERG钾电流抑制作用增强。This study is designed to investigate the effects of chinfloxacin hydrochloride（CFX） on the kinetics of HERG K＋ channel.Whole cell patch clamp technique was used to record HERG K＋ currents from HEK293 cells transiently transfected with cgi-HERG-GFP plasmids and channel kinetics were assessed in the absence and presence of CFX and moxifloxacin hydrochloride（MOX）.Results demonstrated that the open state of HERG K＋ channel was inhibited by CFX in a concentration-and time-dependent manner,with an IC50 of 162.1 ± 14.2 μmol.L？1,two folds higher than its positive control MOX.But there were no significant effects on channel kinetics.In addition,the inhibitory effect of CFX on HERG was enhanced when cells were subjected to altered extracellular K＋ concentration.

关 键 词：盐酸昌欣沙星 HERG钾离子通道 氟喹诺酮 

分 类 号：R966[医药卫生—药理学] R978.69[医药卫生—药学]