KCNE4 is an inhibitory subunit to the KCNQ1 channel
KCNE4 is an inhibitory subunit to the KCNQ1 channel
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DOI：
10.1113/jphysiol.2002.017301
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发表时间：
2002-07-01
影响因子：
5.5
通讯作者：
Klaerke, DA
中科院分区：
文献类型：
--
作者：
Grunnet, M;Jespersen, T;Klaerke, DA
KCNE 4是属于已知对某些钾通道的门控具有显著影响的单跨膜结构域蛋白家族的膜蛋白。然而，到目前为止还没有KCNE 4的功能作用。在本文中，我们证明，KCNE 4是KCNQ 1通道的抑制亚基。KCNQ 1和KCNE 4在爪蟾卵母细胞中的共表达完全抑制KCNQ 1电流。这在哺乳动物CHO-K1细胞中重现。在表达KCNQ 1的卵母细胞中延迟表达编码KCNE 4的mRNA的实验表明，KCNE 4对已经在质膜中表达的KCNQ 1通道发挥作用。这一观点得到了免疫细胞化学研究和蛋白质印迹法的支持，表明在KCNE 4存在或不存在的情况下，KCNQ 1通道的质膜表达没有显着差异。KCNE 4对KCNQ 1的影响是特异性的，因为如果与KCNQ 2 -5通道或hERG 1通道共表达，则无法检测到KCNE 4的影响。RT-PCR研究显示KCNE 4在胚胎和成年子宫中高表达，其中KCNQ 1通道的显着表达也已被证明。
KCNE4 is a membrane protein belonging to a family of single transmembrane domain proteins known to have dramatic effect on the gating of certain potassium channels. However, no functional role of KCNE4 has been suggested so far. In the present paper we demonstrate that KCNE4 is an inhibitory subunit to KCNQ1 channels. Co-expression of KCNQ1 and KCNE4 in Xenopus oocytes completely inhibited the KCNQ1 current. This was reproduced in mammalian CHO-K1 cells. Experiments with delayed expression of mRNA coding for KCNE4 in KCNQ1-expressing oocytes suggested that KCNE4 exerts its effect on KCNQ1 channels already expressed in the plasma membrane. This notion was supported by immunocytochemical studies and Western blotting, showing no significant difference in plasma membrane expression of KCNQ1 channels in the presence or absence of KCNE4. The impact of KCNE4 on KCNQ1 was specific since no effect of KCNE4 could be detected if co-expressed with KCNQ2-5 channels or hERG1 channels. RT-PCR studies revealed high KCNE4 expression in embryos and adult uterus, where significant expression of KCNQ1 channels has also been demonstrated.