普罗帕酮对Kv1.4通道内口突变前后的影响  

Effect of propafenone on Kv1.4 channel before and after inner pore mouth mutation.

作　　者：李绪勇[1] 李晓艳[1] 蒋学俊[1] 徐林[1] 

机构地区：[1]武汉大学人民医院心血管内科,湖北武汉430060

出　　处：《中国心脏起搏与心电生理杂志》2009年第1期55-58,共4页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：国家自然科学基金资助项目(项目编号:30270362);湖北省卫生厅青年人才基金(项目编号:QJX2005-8);湖北省十一五科技攻关项目(项目编号:2006AA301A04)

摘　　要：目的探讨普罗帕酮对编码瞬时外向钾电流(Ito)慢通道Kv1.4通道(fKv1.4ΔN)内口突变(fKv1.4[V561A]ΔN)前后的影响。方法将fKv1.4ΔN和fKv1.4[V561A]ΔN的cRNA注射到非洲爪蟾卵母细胞,孵育24～72 h后使用不同刺激程序用双微电极法记录通道电流的表达。用Clampfit 9.0对数据进行分析。部分电流用相应的方程拟合。结果普罗帕酮对fKv1.4ΔN和fKv1.4[V561A]ΔN的阻滞效应都呈电压和频率依赖性。通道内口的V561A突变使fKv1.4ΔN通道与普罗帕酮的结合能力减小,50%抑制浓度(IC50)在突变前后分别为100μmol/L和380μmol/L(P<0.01)。普罗帕酮能改变fKv1.4ΔN和fKv1.4[V561A]ΔN的失活特性。尽管普罗帕酮对fKv1.4ΔN的失活后恢复没有影响,但是它能延长fKv1.4[V561A]ΔN的50%失活后恢复时间。结论普罗帕酮是fKv1.4ΔN通道的开放通道阻滞剂,fKv1.4ΔN通道内口突变(V561A)能改变普罗帕酮与通道之间的结合能力,从而影响通道的失活和失活后恢复。Objective To discuss the effect of propafenone on the Kv1.4 channel（fKv1.4△N） ,which encodes a slow recovering transient outward current （ I10）, before and after the channel inner pore mouth mutation. Methods fKv1. 4AN and fKv1. 4[ V561A] AN cRNAs, were injected in Xenopus laevis oocytes. After 24 -72 hours incubation, currents were recorded by two-microelectrode voltage clamp technique using different depolarizing protocols. The data was analyzed with Clampfit 9.0 software. Some current traces were fitted with corresponding equations. Results The effects of propafenone on fKv1. dAN and fKv1. 4[ V561A] AN channel were both in voltage- and frequent- dependent manners. The binding ability of propafenone on fKv1. 4AN channel decreased after V561A mutation. Propafenone＇ s ICs0 was 100μmol/L and 380 μmol/L before and after mutation respectively（P 〈 0.01 ）. Propafenone altered the inactivation of fKv1. 4AN and fKv1. 4[ V561A] AN channels. Despite of no effect on fKv1. 4AN channel＇s recovery, propafenone can prolong the 50% re- covery time in fKv1.4[V561A]AN channe1. Conclusions Propafenone is an open channel blocker of fKv1.4AN,whose binding ability to this channel can be reduced by inner pore mouth mutation （V561A）. Moreover the drug can shift the character of the inactivation and recovery from inactivation of the channe1. [ Chinese Journal of Cardiac Pacing and Electro- physiology,2009,23 （ 1 ） ：55 - 58 ]

关 键 词：电生理学 Kv1.4通道 普罗帕酮 突变 c型失活 

分 类 号：R331.38[医药卫生—人体生理学] R972.2[医药卫生—基础医学]