KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels
KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels
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DOI：
10.1016/s0006-3495(03)74585-8
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发表时间：
2003-09-01
影响因子：
3.4
通讯作者：
Jespersen, T
中科院分区：
文献类型：
--
作者：
Grunnet, M;Rasmussen, HB;Jespersen, T
Kv 1钾通道广泛分布于哺乳动物的组织中，参与多种功能，包括调控细胞内钾离子的浓度、细胞内钾离子的浓度、细胞内钾离子的浓度、细胞内钾离子的浓度等。T淋巴细胞成熟的神经元环速率。在这里，我们表明，新描述的KCNE 4 β亚基对Kv1.1和Kv1.3钾通道产生的电流具有强烈的抑制作用。在非洲爪蟾卵母细胞和哺乳动物HEK 293细胞中异源表达的通道上发现抑制。mKCNE 4不抑制Kv1.2、Kv1.4、Kv1.5或Kv4.3同聚复合物，但可显著降低通过Kv1.1/Kv1.2和Kv1.2/ Kv1.3异聚复合物的电流。共聚焦显微镜和蛋白质印迹法显示Kv1.1与KCNE 4一起存在于细胞表面。实时RT-PCR显示mKCNE 4 mRNA在几个器官中相对较高，包括子宫，肾脏，肺，肠和胚胎，而在心脏和大脑的五个不同部位检测到低得多的mRNA水平。考虑到Kv 1通道的广泛分布，KCNE 4亚基的抑制特性可以局部和/或瞬时对细胞兴奋性和静息膜电位的设定产生显著影响。
Kv1 potassium channels are widely distributed in mammalian tissues and are involved in a variety of functions from controlling the. ring rate of neurons to maturation of T-lymphocytes. Here we show that the newly described KCNE4 beta-subunit has a drastic inhibitory effect on currents generated by Kv1.1 and Kv1.3 potassium channels. The inhibition is found on channels expressed heterologously in both Xenopus oocytes and mammalian HEK293 cells. mKCNE4 does not inhibit Kv1.2, Kv1.4, Kv1.5, or Kv4.3 homomeric complexes, but it does significantly reduce current through Kv1.1/Kv1.2 and Kv1.2/ Kv1.3 heteromeric complexes. Confocal microscopy and Western blotting reveal that Kv1.1 is present at the cell surface together with KCNE4. Real-time RT-PCR shows a relatively high presence of mKCNE4 mRNA in several organs, including uterus, kidney, lung, intestine, and in embryo, whereas a much lower mRNA level is detected in the heart and in five different parts of the brain. Having the broad distribution of Kv1 channels in mind, the demonstrated inhibitory property of KCNE4-subunits could locally and/or transiently have a dramatic influence on cellular excitability and on setting resting membrane potentials.