Kir2.1 channels set two levels of resting membrane potential with inward rectification.
Kir2.1 channels set two levels of resting membrane potential with inward rectification.
复制标题
Kir2.1 通道通过内向整流设置两个水平的静息膜电位
DOI：
10.1007/s00424-017-2099-3
复制
发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Chen K;Zuo D;Liu Z;Chen H
强大的内向整流性K+通道(Kir2.1)主要调节维持静息膜电位的背景K+电流。多种类型的细胞表现出两个水平的静息膜电位。Kir2.1和K2P1电流相互抵消，部分解释了人心肌细胞在亚生理性细胞外K+浓度或病理性低血钾条件下的现象。Kir2.1通道如何在不同类型的细胞中对静息膜电位的两个水平起作用的机制尚不清楚。在这里，我们检验了Kir2.1通道通过内向整流设置两个水平的静息膜电位的假设。在低钾条件下，Kir2.1电流抵消了CHO细胞中异源表达两个通道的HCN2或HCN4阳离子电流，产生了三次跨越电压轴的N型电流-电压关系，并重建了两个水平的静息膜电位。阻断HCN通道可以消除K2P1缺陷的人心肌细胞表达Kir2.1的现象，这些细胞来自诱导的多能干细胞或同时表达Kir2.1和HCN2通道的CHO细胞。弱的内向整流通道Kir4.1或内向整流缺陷的Kir2.1·E224G突变通道在CHO细胞中与HCN2通道共表达或在诱导多能干细胞来源的人心肌细胞中过表达时，不能设置这两个水平的静息膜电位。这些发现证明了一个共同的机制，即Kir2.1通道通过平衡不同阳离子通道(如超极化激活的HCN通道或低钾诱导的K2P1泄漏通道)的内向电流来设置两个水平的静息膜电位和内向整流。
Strong inward rectifier K+channels (Kir2.1) mediate background K+currents primarily responsible for maintenance of resting membrane potential. Multiple types of cells exhibit two levels of resting membrane potential. Kir2.1 and K2P1 currents counterbalance, partially accounting for the phenomenon of human cardiomyocytes in subphysiological extracellular K+concentrations or pathological hypokalemic conditions. The mechanism of how Kir2.1 channels contribute to the two levels of resting membrane potential in different types of cells is not well understood. Here we test the hypothesis that Kir2.1 channels set two levels of resting membrane potential with inward rectification. Under hypokalemic conditions, Kir2.1 currents counterbalance HCN2 or HCN4 cation currents in CHO cells that heterologously express both channels, generating N-shaped current-voltage relationships that cross the voltage axis three times and reconstituting two levels of resting membrane potential. Blockade of HCN channels eliminated the phenomenon in K2P1-deficient Kir2.1-expressing human cardiomyocytes derived from induced pluripotent stem cells or CHO cells expressing both Kir2.1 and HCN2 channels. Weakly inward rectifier Kir4.1 or inward rectification-deficient Kir2.1•E224G mutant channels do not set such two levels of resting membrane potential when co-expressed with HCN2 channels in CHO cells or when overexpressed in human cardiomyocytes derived from induced pluripotent stem cells. These findings demonstrate a common mechanism that Kir2.1 channels set two levels of resting membrane potential with inward rectification by balancing inward currents through different cation channels such as hyperpolarization-activated HCN channels or hypokalemia-induced K2P1 leak channels.
登录
查看更多内容
DOI：
10.1085/jgp.70.6.725
发表时间：
1977-12
期刊：
The Journal of general physiology
影响因子：
--
作者：
Gadsby DC;Cranefield PF
通讯作者：
Cranefield PF
影响因子：
5.5
作者：
ELLIS, D
通讯作者：
ELLIS, D
影响因子：
10.8
作者：
CHRISTE, G
通讯作者：
CHRISTE, G
影响因子：
3.8
作者：
Miura, D S;Hoffman, B F;Rosen, M R
通讯作者：
Rosen, M R
影响因子：
7.3
作者：
Ma, Liqun;Zhang, Xuexin;Chen, Haijun
通讯作者：
Chen, Haijun