阿司咪唑阻断HERG通道的生物学特性及分子机制  

Biophysical properties and molecular mechanism of HERG channels blockade by astemizole

作　　者：涂丹娜[1] 廖玉华[1] 邹安若[1] 杜以梅[1] 肖华[1] 王宪沛[1] 李璐[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院,湖北武汉430022

出　　处：《山东医药》2008年第29期4-6,共3页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(编号:30470711)

摘　　要：目的观察阿司咪唑对野生型和Y652突变型HERG通道阻断的生物物理学特性,探讨HERG通道分子位点改变对阻断的影响。方法将HERG通道表达于非洲爪蟾卵母细胞,利用双电极电压钳技术测量其电流,观察阿司咪唑不同浓度、不同电压、不同作用时间下,对野生型和Y652A、Y652R突变型HERG通道电流的阻断作用。结果阿司咪唑以电压、浓度、时间依赖性阻断HERG通道电流;与野生型比较,Y652A和Y652R突变型可显著减弱阿司咪唑对HERG通道的阻断作用。结论阿司咪唑优先阻断开放状态的HERG通道,Y652是阿司咪唑与通道结合的关键位点,其极性和侧链长度改变可影响阿司咪唑与通道结合。Objective To investigate the inhibitory action of astemizole on wild type （WT） and Y652 mutational HERG channels and observe the molecular mechanism. Methods HERG channels were expressed in Xenopus oocytes, and currents were measured using two-microelectrode voltage-clamp technique. The effects of astemizole on HERG channels blockade were observed. Results Astemizole blocked HERG current in voltage-concentration-and time-dependent manner. Compared with the WT, Y652A and Y652R significantly attenuated the blockade by astemizolc. Conclusion Astemizole preferentially blocks open state HERG channel. Compared with the WT-652 is a critical residue in the astemizole-binding site.

关 键 词：HERG 钾通道 电压钳技术 阿司咪唑 突变 

分 类 号：R972[医药卫生—药品]