Lack of negatively charged residues at the external mouth of Kir2.2 channels enable the voltage-dependent block by external Mg2+.
Lack of negatively charged residues at the external mouth of Kir2.2 channels enable the voltage-dependent block by external Mg2+.
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Kir2.2 通道外部口处缺乏带负电的残留物，可通过外部 Mg2 实现电压相关模块
DOI：
10.1371/journal.pone.0111372
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
An H
中科院分区：
文献类型：
--
作者：
Li J;Xie X;Liu J;Yu H;Zhang S;Zhan Y;Zhang H;Logothetis DE;An H
Kir通道显示由胞质阳离子如Mg 2+和多胺引起的电压依赖性阻断，其引起向内整流。事实上，阳离子可以从细胞外和细胞内两方面调节K通道活性。以前的研究提供了洞察Kir通道活性的上调细胞外K+浓度。相比之下，细胞外Mg 2+已被发现，以降低在毫摩尔浓度的单通道电流的幅度。然而，外界Mg ~（2+）阻断Kir通道的分子机制以及Mg ~（2+）阻断与渗透性K ~+离子增强活性之间的关系知之甚少。在本研究中，我们采用了理论和实验之间的互动方法。通过在非洲爪蟾卵母细胞中异源表达Kir2.2及其突变体进行电生理记录。我们的研究结果证实，细胞外Mg 2+可以降低异源表达的WT Kir2.2电流的电压依赖性方式。Mg ~（2+）的抑制和恢复动力学的时间常数为3 × 10 ~（-4）s。分子动力学模拟结果显示，镁离子结合位点位于胞外口的Kir2.2，显示电压依赖性镁离子结合。突变体，G119 D，Q126 E和H128 D，增加了渗透性K+离子的数量，减少了细胞外Mg 2+对Kir2.2的电压依赖性阻断。
Kir channels display voltage-dependent block by cytosolic cations such as Mg2+ and polyamines that causes inward rectification. In fact, cations can regulate K channel activity from both the extracellular and intracellular sides. Previous studies have provided insight into the up-regulation of Kir channel activity by extracellular K+ concentration. In contrast, extracellular Mg2+ has been found to reduce the amplitude of the single-channel current at milimolar concentrations. However, little is known about the molecular mechanism of Kir channel blockade by external Mg2+ and the relationship between the Mg2+ blockade and activity potentiation by permeant K+ ions. In this study, we applied an interactive approach between theory and experiment. Electrophysiological recordings on Kir2.2 and its mutants were performed by heterologous expression in Xenopus laevis oocytes. Our results confirmed that extracellular Mg2+ could reduce heterologously expressed WT Kir2.2 currents in a voltage dependent manner. The kinetics of inhibition and recovery of Mg2+ exhibit a 3∼4s time constant. Molecular dynamics simulation results revealed a Mg2+ binding site located at the extracellular mouth of Kir2.2 that showed voltage-dependent Mg2+ binding. The mutants, G119D, Q126E and H128D, increased the number of permeant K+ ions and reduced the voltage-dependent blockade of Kir2.2 by extracellular Mg2+.
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影响因子：
64.8
作者：
Hansen, Scott B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
DOI：
10.1098/rspb.1991.0053
发表时间：
1991-05-22
影响因子：
4.7
作者：
KONNO, T;BUSCH, C;SAKMANN, B
通讯作者：
SAKMANN, B
MG2+在主动脉内皮细胞中向内整流的K+通道失活中的作用。
DOI：
10.1085/jgp.105.4.463
发表时间：
1995-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
Elam TR;Lansman JB
通讯作者：
Lansman JB
影响因子：
2.9
作者：
MACKINNON, R;LATORRE, R;MILLER, C
通讯作者：
MILLER, C