Kir2.1 and K2P1 channels reconstitute two levels of resting membrane potential in cardiomyocytes
Kir2.1 and K2P1 channels reconstitute two levels of resting membrane potential in cardiomyocytes
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Kir2.1 和 K2P1 通道重建心肌细胞中两个水平的静息膜电位
DOI：
10.1113/jp274268
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Haijun Chen
中科院分区：
文献类型：
--
作者：
Dongchuan Zuo;Kuihao Chen;Min Zhou;Zheng Liu;Haijun Chen
跨细胞膜的外向和内向背景电流平衡，决定静息膜电位。内向整流钾通道亚家族2（Kir 2）主要维持心肌细胞的静息膜电位。人心肌细胞在亚生理性细胞外钾浓度或病理性低钾血症时表现出两种水平的静息膜电位，然而，其内在机制尚不清楚。在本研究中，我们发现，来自诱导多能干细胞的人心肌细胞具有Kir 2（Kir2.1）通道亚型1的增强表达，小鼠HL-1心肌细胞具有两个孔域K+通道亚型1（K2 P1）的异位表达，重现了两个水平的静息膜电位，表明Kir2.1和K2 P1通道对该现象的贡献。在表达通道的中国仓鼠卵巢细胞中，Kir2.1电流非线性地抵消低钾血症诱导的K2 P1漏阳离子电流，重建两个水平的静息膜电位。这些发现支持了Kir 2电流非线性地平衡内向背景阳离子电流（如K2 P1电流）的假设，解释了人类心肌细胞中两个水平的静息膜电位，并证明了一种调节兴奋性的新机制。
Outward and inward background currents across the cell membrane balance, determining resting membrane potential. Inward rectifier K+ channel subfamily 2 (Kir2) channels primarily maintain the resting membrane potential of cardiomyocytes. Human cardiomyocytes exhibit two levels of resting membrane potential at subphysiological extracellular K+ concentrations or pathological hypokalaemia, however, the underlying mechanism is unclear. In the present study, we show that human cardiomyocytes derived from induced pluripotent stem cells with enhanced expression of isoform 1 of Kir2 (Kir2.1) channels and mouse HL‐1 cardiomyocytes with ectopic expression of two pore‐domain K+ channel isoform 1 (K2P1) recapitulate two levels of resting membrane potential, indicating the contributions of Kir2.1 and K2P1 channels to the phenomenon. In Chinese hamster ovary cells that express the channels, Kir2.1 currents non‐linearly counterbalance hypokalaemia‐induced K2P1 leak cation currents, reconstituting two levels of resting membrane potential. These findings support the hypothesis that Kir2 currents non‐linearly counterbalance inward background cation currents, such as K2P1 currents, accounting for two levels of resting membrane potential in human cardiomyocytes and demonstrating a novel mechanism that regulates excitability.
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影响因子：
11.4
作者：
Lesage, F;Guillemare, E;Barhanin, J
通讯作者：
Barhanin, J
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：
Bett, Glenna C. L.;Kaplan, Aaron D.;Lis, Agnieszka;Cimato, Thomas R.;Tzanakakis, Emmanuel S.;Zhou, Qinlian;Morales, Michael J.;Rasmusson, Randall L.
通讯作者：
Rasmusson, Randall L.
影响因子：
5.5
作者：
Gaborit, Nathalie;Le Bouter, Sabrina;Demolombe, Sophie
通讯作者：
Demolombe, Sophie
DOI：
10.1093/europace/eup005
发表时间：
2008-12
期刊：
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
影响因子：
--
作者：
A. Zaza
通讯作者：
A. Zaza