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|本期目录/Table of Contents|

钾离子通道β亚单位KCNE4对KCNQ1及HERG电流的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第2期
页码:
129-133139
栏目:
专家论坛
出版日期:
2013-04-25

文章信息/Info

Title:
Effect of KCNE4 subunit on potassium ion channel KCNQ1 and HERG
作者:
马克娟1; 浦介麟2; 郭成军1; 张英川1
(1.首都医科大学附属北京安贞医院心电生理科，北京 100029；2.中国医学科学院阜外心血管病医院心律失常诊治中心、病理与生理实验室，北京 100037)
Author(s):
MA Ke-juan1;  PU Jie-lin2;  GUO Cheng-jun1;  ZHANG Ying-chuan1
(1.Department of Cardiac Electrophysiology, Beijing An Zhen Hospital, Capital Medical University, Beijing 100029, China; 2.Center for Arrhythmia Diagnosis and Treatment & Pathology and Physiology Lab, Fuwai Cardiovascular Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China)
关键词:
KCNE4; 钾离子通道; KCNQ1; HERG; 膜片钳; 膜电流
Keywords:
KCNE4;  potassium channels;  KCNQ1;  HERG;  patch clamp;  membrane currents
分类号:
R329.25
DOI:
-
文献标识码:
A
摘要:
目的:研究钾离子通道β亚单位KCNE4对KCNQ1及HERG通道电流的影响。方法： 构建离子通道细胞模型，单独表达基因KCNQ1、HERG，以及联合表达基因KCNQ1+KCNE4、HERG+KCNE4。采用全细胞膜片钳方法记录通道电流曲线，比较组间电流的大小及通道的动力学特征。采用免疫荧光细胞定位方法，检测KCNE4对通道蛋白表达的影响。结果： KCNE4与 KCNQ1共表达显著减低KCNQ1通道电流。单独表达KCNQ1通道的细胞，膜电位+60 mV时，平均电流密度为(24±2.9) pA/pF，共表达KCNQ1+KCNE4时，细胞电流密度降至(7.3±1.1) pA/pF。与KCNQ1电流相比，+40 mV时KCNQ1/KCNE4激活时间常数的快成分(τfast)增加，但慢成分(τslow)减慢，KCNQ1/KCNE4无尾电流产生，表明KCNE4参与了KCNQ1通道动力学的调整。单独表达KCNE4亚单位的细胞没有产生任何电流。当KCNE4与HERG共表达时，电流的大小、电流电压关系曲线及通道稳态激活曲线都与HERG通道无明显差异，电流密度为(26.7±3.9) pA/pF，半数激活电压(V1/2)为(-3.10±0.68) mV，斜率因子为8.89±0.33。从通道的失活时间常数以及失活后恢复时间常数与测试电压的关系曲线可见，KCNE4对HERG通道的动力学特征均无影响。免疫荧光染色结果显示，KCNE4没有影响KCNQ1蛋白的表达。结论： KCNE4亚单位可显著改变KCNQ1通道的电压敏感性，表现出抑制作用，KCNE4对KCNQ1蛋白在细胞膜上的表达及HERG通道电流均无影响。
Abstract:
AIM:To study the influence of KCNE4 on potassium ion channel KCNQ1 and HERG. METHOD: We constructed KCNE4 expression plasmids and performed whole-cell patch-clamp recording on cells cotransfected with KCNQ1 or HERG to identify potential functional consequences. Immunocytochemistry was used to study protein colocalization. RESULTS: The presence of KCNE4 resulted in a dramatic decrease of the KCNQ1 current and produced almost undetectable currents between -80 mV and +60 mV. KCNQ1-expressing cells showed a slowly activating, noninactivating voltage-dependent current ［current density (24±2.9) pA/pF recorded at +60 mV］. In KCNQ1+KCNE4 co-expressing cells, the current density decreased to (7.3±1.1) pA/pF at +60 mV. Expression of KCNE4 alone did not yield any current. Furthermore, the differences between KCNQ1 and KCNQ1/KCNE4 currents were also found in the time course of activation and deactivation, suggesting that KCNE4 can participate in kinetic control of KCNQ1 channel. Subcellular localization study showed the same plasma membrane fluorescence pattern of KCNQ1 when co-expressed with KCNE4, implying that KCNE4 had no effect on the protein trafficking and localization of KCNQ1. There were no differences between HERG and HERG/KCNE4 in the current density and the kinetics control of HERG channel. CONCLUSION: Our data suggest that KCNE4 dramatically decreases KCNQ1 current density at physiologically relevant potentials and exerts an inhibitory effect on KCNQ1 channel. KCNE4 has no effect on HERG channel.

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备注/Memo

备注/Memo:
收稿日期：2012-07-25.基金项目：国家自然科学基金青年科学基金项目资助（81200140） 作者简介：马克娟，主治医师，博士 Email:makejuan@tom.com
更新日期/Last Update: 2013-04-28