Co-expression of KCNE2 and KChlP2c modulates the electrophysiologi- cal properties of Kv4.2 current in COS-7 cells  

作　　者：Wen-juan LIU Hai-tang WANG Wei-wei Chen Jian-xin DENG Yong JIANG Jie LIU 

机构地区：[1]Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China

出　　处：《Acta Pharmacologica Sinica》2008年第6期653-660,共8页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China （No 30570418 and 30570940）.

摘　　要：Aim： Several β-subunits have been suggested to modulate the electrophysiological properties of the transient outward current （Ito） in cardiac myocytes, including the obligatory β-subunit K^＋-channel interacting protein （KChIP2） and KCNE2. However, neither KChIP2 nor KCNE2 modulation of Kv4.x （x=2 and/or 3） can fully recapitulate the electrophysiological properties of nativeIto. The present study is to investigate howIto current is modulated when both KChIP2 and KCNE2 are coexpressed. Methods： Kv4.2, KChIP2c, and KCNE2 cDNA were simultaneously transfected into COS-7 cells at a molar ratio of 3：1：1. Whole-cell currents were recorded by the patch-clamp method. Results： In comparison with the current regulated by KChIP2c alone, the co-expression of KCNE2 further slowed Kv4.2 current inactivation kinetics, but diminished KChIP2c-induced positive shift of the voltage-dependent activation of Kv4.2 current. Importantly, co-expression of KCNE2 accelerated the current recovery from inactivation, and caused an ＂overshoot＂ of peak current amplitude during Kv4.2 current recovery, a phenomenon which has been uniquely described for humanIto. However, co-expression of KCNE2 exerted no further effect on Kv4.2 current amplitude, the rate of Kv4.2 current activation and voltage-dependent inactivation. Conclusion： Co-expression of Kv4.2 with KChIP2c and KCNE2, but not with KChIP2c or KCNE2 alone, yields a current profile similar to nativeIto. Both KChIP2c and KCNE2 simultaneously participate in recapitulation of the electrophysiological properties of Ito in cardiac myocytes.Aim： Several β-subunits have been suggested to modulate the electrophysiological properties of the transient outward current （Ito） in cardiac myocytes, including the obligatory β-subunit K^＋-channel interacting protein （KChIP2） and KCNE2. However, neither KChIP2 nor KCNE2 modulation of Kv4.x （x=2 and/or 3） can fully recapitulate the electrophysiological properties of nativeIto. The present study is to investigate howIto current is modulated when both KChIP2 and KCNE2 are coexpressed. Methods： Kv4.2, KChIP2c, and KCNE2 cDNA were simultaneously transfected into COS-7 cells at a molar ratio of 3：1：1. Whole-cell currents were recorded by the patch-clamp method. Results： In comparison with the current regulated by KChIP2c alone, the co-expression of KCNE2 further slowed Kv4.2 current inactivation kinetics, but diminished KChIP2c-induced positive shift of the voltage-dependent activation of Kv4.2 current. Importantly, co-expression of KCNE2 accelerated the current recovery from inactivation, and caused an ＂overshoot＂ of peak current amplitude during Kv4.2 current recovery, a phenomenon which has been uniquely described for humanIto. However, co-expression of KCNE2 exerted no further effect on Kv4.2 current amplitude, the rate of Kv4.2 current activation and voltage-dependent inactivation. Conclusion： Co-expression of Kv4.2 with KChIP2c and KCNE2, but not with KChIP2c or KCNE2 alone, yields a current profile similar to nativeIto. Both KChIP2c and KCNE2 simultaneously participate in recapitulation of the electrophysiological properties of Ito in cardiac myocytes.

关 键 词：transient outward current KV4.2 K^＋-channel interacting protein KCNE2 ELECTROPHYSIOLOGY 

分 类 号：R96[医药卫生—药理学]