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“非传导性” 摇椅钾通道突变体W434F中的宏观钠离子电流

Macroscopic Na+ currents in the "Nonconducting" Shaker potassium channel mutant W434F.

作者信息

Starkus J G, Kuschel L, Rayner M D, Heinemann S H

机构信息

Max-Planck Society, Research Unit Molecular and Cellular Biophysics, D-07747 Jena, Germany.

出版信息

J Gen Physiol. 1998 Jul;112(1):85-93. doi: 10.1085/jgp.112.1.85.

DOI:10.1085/jgp.112.1.85
PMID:9649585
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2229408/
Abstract

C-type inactivation in Shaker potassium channels inhibits K+ permeation. The associated structural changes appear to involve the outer region of the pore. Recently, we have shown that C-type inactivation involves a change in the selectivity of the Shaker channel, such that C-type inactivated channels show maintained voltage-sensitive activation and deactivation of Na+ and Li+ currents in K+-free solutions, although they show no measurable ionic currents in physiological solutions. In addition, it appears that the effective block of ion conduction produced by the mutation W434F in the pore region may be associated with permanent C-type inactivation of W434F channels. These conclusions predict that permanently C-type inactivated W434F channels would also show Na+ and Li+ currents (in K+-free solutions) with kinetics similar to those seen in C-type-inactivated Shaker channels. This paper confirms that prediction and demonstrates that activation and deactivation parameters for this mutant can be obtained from macroscopic ionic current measurements. We also show that the prolonged Na+ tail currents typical of C-type inactivated channels involve an equivalent prolongation of the return of gating charge, thus demonstrating that the kinetics of gating charge return in W434F channels can be markedly altered by changes in ionic conditions.

摘要

果蝇钾通道中的C型失活抑制钾离子通透。相关的结构变化似乎涉及孔道的外部区域。最近,我们发现C型失活涉及果蝇通道选择性的改变,因此C型失活的通道在无钾溶液中表现出维持的电压敏感性激活以及钠离子和锂离子电流的失活,尽管它们在生理溶液中没有可测量的离子电流。此外,孔道区域的W434F突变所产生的离子传导有效阻断似乎与W434F通道的永久性C型失活有关。这些结论预测,永久性C型失活的W434F通道在无钾溶液中也会表现出与C型失活的果蝇通道类似动力学的钠离子和锂离子电流。本文证实了这一预测,并表明该突变体的激活和失活参数可从宏观离子电流测量中获得。我们还表明,C型失活通道典型的延长的钠离子尾电流涉及门控电荷返回的等效延长,从而证明离子条件的变化可显著改变W434F通道中门控电荷返回的动力学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/41642f74062c/JGP7715.f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/1bac33458a22/JGP7715.f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/32fa050536d8/JGP7715.f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/70cb87fc90ff/JGP7715.f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/e04234c0e0f7/JGP7715.f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/41642f74062c/JGP7715.f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/1bac33458a22/JGP7715.f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/32fa050536d8/JGP7715.f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/70cb87fc90ff/JGP7715.f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/e04234c0e0f7/JGP7715.f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b75/2229408/41642f74062c/JGP7715.f5.jpg

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本文引用的文献

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Biophys J. 1998 Apr;74(4):1840-9. doi: 10.1016/S0006-3495(98)77894-4.
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Correlation between charge movement and ionic current during slow inactivation in Shaker K+ channels.Shaker钾离子通道缓慢失活过程中电荷移动与离子电流之间的相关性。
J Gen Physiol. 1997 Nov;110(5):579-89. doi: 10.1085/jgp.110.5.579.
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Ion conduction through C-type inactivated Shaker channels.离子通过C型失活的Shaker通道的传导。
bioRxiv. 2024 Aug 10:2023.06.02.543446. doi: 10.1101/2023.06.02.543446.
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When Is a Potassium Channel Not a Potassium Channel?当一个钾离子通道不是一个钾离子通道时,它是什么?
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The nonconducting W434F mutant adopts upon membrane depolarization an inactivated-like state that differs from wild-type Shaker-IR potassium channels.非传导性的W434F突变体在膜去极化时会呈现出一种与野生型Shaker-IR钾通道不同的失活样状态。
Sci Adv. 2022 Sep 16;8(37):eabn1731. doi: 10.1126/sciadv.abn1731.
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Regulation of K Conductance by a Hydrogen Bond in Kv2.1, Kv2.2, and Kv1.2 Channels.Kv2.1、Kv2.2和Kv1.2通道中氢键对钾离子电导的调节
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The C-terminal HRET sequence of Kv1.3 regulates gating rather than targeting of Kv1.3 to the plasma membrane.Kv1.3 的 C 端 HRET 序列调节门控而不是 Kv1.3 向质膜的靶向。
Sci Rep. 2018 Apr 12;8(1):5937. doi: 10.1038/s41598-018-24159-8.
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Dynamics of the EAG1 K channel selectivity filter assessed by molecular dynamics simulations.通过分子动力学模拟评估EAG1钾通道选择性过滤器的动力学
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Allosteric effects of permeating cations on gating currents during K+ channel deactivation.钾离子通道失活过程中渗透阳离子对门控电流的变构效应。
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