KCNE3 is an inhibitory subunit of the Kv4.3 potassium channel

被引:26
作者
Lundby, Alicia [1 ]
Olesen, Soren-Peter [1 ]
机构
[1] Univ Copenhagen, Panum Inst, Danish Natl Res Fdn, Ctr Cardiac Arrhythmia,Dept Med Physiol, DK-2200 Copenhagen N, Denmark
关键词
voltage-gated potassium channel; I-to current; inhibitory beta-subunit; MIRP2; Kv4.3; KCND3; KCNE3;
D O I
10.1016/j.bbrc.2006.06.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mammalian Kv4.3 potassium channel is a fast activating and inactivating K+ channel widely distributed in mammalian tissues. Kv4.3 is the major component of various physiologically important currents ranging from A-type currents in the CNS to the transient outward potassium conductance in the heart (I-to). Here we show that the KCNE3 beta-subunit has a strong inhibitory effect on current conducted by heterologously expressed Kv4.3 channels. KCNE3 reduces the Kv4.3 current amplitude, and it slows down the channel activation and inactivation as well as the recovery from inactivation. KCNE3 also inhibits currents generated by Kv4.3 in complex with the accessory subunit KChIP2. We find the inhibitory effect of KCNE3 to be specific for Kv4.3 within the Kv4 channel family. Kv4.3 has previously been shown to interact with a number of beta-subunits, but none of the described subunit-interactions exert an inhibitory effect on the Kv4.3 current. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:958 / 967
页数:10
相关论文
共 34 条
[11]   Role of the Kv4.3 K+ channel in ventricular muscle - A molecular correlate for the transient outward current [J].
Dixon, JE ;
Shi, WM ;
Wang, HS ;
McDonald, C ;
Yu, H ;
Wymore, RS ;
Cohen, IS ;
McKinnon, D .
CIRCULATION RESEARCH, 1996, 79 (04) :659-668
[12]   KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels [J].
Grunnet, M ;
Rasmussen, HB ;
Hay-Schmidt, A ;
Rosenstierne, M ;
Klaerke, DA ;
Olesen, SP ;
Jespersen, T .
BIOPHYSICAL JOURNAL, 2003, 85 (03) :1525-1537
[13]   KCNE4 is an inhibitory subunit to the KCNQ1 channel [J].
Grunnet, M ;
Jespersen, T ;
Rasmussen, HB ;
Ljungstrom, T ;
Jorgensen, NK ;
Olesen, SP ;
Klaerke, DA .
JOURNAL OF PHYSIOLOGY-LONDON, 2002, 542 (01) :119-130
[14]   Role of heteromultimers in the generation of myocardial transient outward K+ currents [J].
Guo, WN ;
Li, HL ;
Aimond, F ;
Johns, DC ;
Rhodes, KJ ;
Trimmer, JS ;
Nerbonne, JM .
CIRCULATION RESEARCH, 2002, 90 (05) :586-593
[15]  
Hille B., 2001, Ion channels of excitable membranes, V3rd
[16]   Molecular basis of transient outward potassium current downregulation in human heart failure -: A decrease in Kv4.3 mRNA correlates with a reduction in current density [J].
Kääb, S ;
Dixon, J ;
Duc, J ;
Ashen, D ;
Näbauer, M ;
Beuckelmann, DJ ;
Steinbeck, G ;
McKinnon, D ;
Tomaselli, GF .
CIRCULATION, 1998, 98 (14) :1383-1393
[17]   Ito channels are octomeric complexes with four subunits of each Kv4.2 and K+ channel-interacting protein 2 [J].
Kim, LA ;
Furst, J ;
Butler, MH ;
Xu, SH ;
Grigorieff, N ;
Goldstein, SAN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (07) :5549-5554
[18]  
KONG W, 1998, AM J PHYSIOL, V275, P1963
[19]   A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of Ito and confers susceptibility to ventricular tachycardia [J].
Kuo, HC ;
Cheng, CF ;
Clark, RB ;
Lin, JJC ;
Lin, JLC ;
Hoshijima, M ;
Nguyêñ-Trân, VTB ;
Gu, YS ;
Ikeda, Y ;
Chu, PH ;
Ross, J ;
Giles, WR ;
Chien, KR .
CELL, 2001, 107 (06) :801-813
[20]  
McCrossan ZA, 2003, J NEUROSCI, V23, P8077