hKCNE4 inhibits the hKCNQ1 potassium current without affecting the activation kinetics
hKCNE4 inhibits the hKCNQ1 potassium current without affecting the activation kinetics
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DOI：
10.1016/j.bbrc.2005.01.071
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发表时间：
2005-03-25
影响因子：
3.1
通讯作者：
Jespersen, T
中科院分区：
文献类型：
--
作者：
Grunnet, M;Olesen, SP;Jespersen, T
kcnne β亚基家族的所有五个成员都能够调节KCNQ1钾电流。我们之前发表过KCNE4的小鼠变体抑制人类KCNQ1电流[J]。生理学报。542(2002)119]。最近，这一发现受到了Teng等人的挑战，他们指出KCNE4的人类变体不会减弱KCNQ1电流，但在非洲爪蟾卵母细胞中表达后，会略微调节该通道的激活动力学[Biochem]。Biophys。参考文献。303(2003)808]。在本研究中，我们对人和鼠KCNE4影响人和鼠KCNQ1电流的能力进行了详细的研究。我们发现hKCNE4亚基在X. laevis卵母细胞中表达后显著抑制hKCNQ1电流。当这些亚基中的任何一个与mKCNQ1共表达时，对hKCNE4和mKCNE4也观察到这种抑制作用。对hKCNQ1电流性质的分析表明，活化动力学与hKCNE4的存在无关。然而，hKCNE4具有防止KCNQ1电流失活的能力。综合前人的研究和本研究结果，我们认为hKCNE4和mKCNE4对hKCNQ1和mKCNQ1电流都有明显的抑制作用。(C) 2005爱思唯尔公司版权所有。
All five members of the KCNE beta-subunit family are capable of modulating the KCNQ1 potassium current. We have previously published that the murine variant of KCNE4 inhibits the human KCNQ1 current [J. Physiol. 542(2002) 119]. Recently, this finding has been challenged by Teng et al, stating that the human variant of KCNE4 does not attenuate the KCNQ1 current but does slightly modulate the activation kinetics of the channel after expression in Xenopus laevis oocytes [Biochem. Biophys. Res. Commun. 303 (2003) 808]. In the present study, a detailed investigation on the ability of human and murine KCNE4 to affect either human or murine KCNQ1 currents has been performed. We find that the hKCNE4 subunit drastically inhibits the hKCNQ1 current after expression in X. laevis oocytes. This inhibitory effect is also observed for both hKCNE4 and mKCNE4 when either of these subunits is co-expressed with mKCNQ1. Analyses of the current properties of hKCNQ1 revealed that activation kinetics are independent of the presence of hKCNE4. hKCNE4 has, however, the ability to prevent the inactivation observed for the KCNQ1 current. Based upon previous studies and the present results, it is concluded that both hKCNE4 and mKCNE4 have a drastic inhibitory impact on both hKCNQ1 and mKCNQ1 currents. (C) 2005 Elsevier Inc. All rights reserved.