Control of outer vestibule dynamics and current magnitude in the Kv2.1 potassium channel.
Control of outer vestibule dynamics and current magnitude in the Kv2.1 potassium channel.
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DOI：
10.1085/jgp.20028639
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发表时间：
2002-11
期刊：
影响因子：
--
通讯作者：
Korn SJ
中科院分区：
文献类型：
--
作者：
Andalib P;Wood MJ;Korn SJ
在Kv2.1钾通道中，外部[K+]的变化调节电流大小，这是两种外前庭构象之间K+依赖性相互转换的结果。以前的证据表明，外前庭构象（因此电流大小）是由K+的选择性过滤器结合位点的占用率。在本文中，我们使用的电流大小的变化作为分析，研究如何控制外前庭构象之间的相互转换。在100 mM内部K+的情况下，当通道被激活时，外部[K+]从0到10 mM的快速升高不会产生电流大小的变化（外前庭构象没有变化）。当通道随后关闭并在[K+]升高的情况下重新打开时，电流幅度增加（外前庭构象发生变化）。当通道在低的内部[K+]存在下被激活时，或者当K+流入传导通道被内部通道阻断剂短暂中断时，在激活期间增加外部[K+]确实增加了电流幅度（通道构象确实改变）。这些数据表明，当通道在生理条件下处于激活状态时，尽管外部[K+]发生变化，但外前庭构象仍保持固定。相反，当通道占用率降低时（通过通道关闭，内部阻断剂或低内部[K+]），外前庭可以在两种构象之间相互转换。我们讨论的证据表明，外前庭构象的变化的能力是由K+的非选择性过滤器网站的占用率。独立于外前庭增强机制，Kv2.1对影响电流大小的K+依赖性过程非常不敏感（在−20和30 mV之间的膜电位下，电流大小变化<7%）。用较小的中性氨基酸替换Kv2.1中的两个外前庭赖氨酸使得电流幅度对K+驱动力的降低显着更敏感（电流幅度变化高达40%）。当结合时，这些外前庭特性（活化期间的固定构象和赖氨酸的存在）几乎阻止了当[K+]在活化期间改变时Kv2.1电流幅度的变化。此外，Kv2.1电流大小的K+驱动力的变化的不敏感性，促进了一个更均匀的调制电流在很宽的范围内的膜电位的K+依赖性调节外前庭构象。
In Kv2.1 potassium channels, changes in external [K+] modulate current magnitude as a result of a K+-dependent interconversion between two outer vestibule conformations. Previous evidence indicated that outer vestibule conformation (and thus current magnitude) is regulated by the occupancy of a selectivity filter binding site by K+. In this paper, we used the change in current magnitude as an assay to study how the interconversion between outer vestibule conformations is controlled. With 100 mM internal K+, rapid elevation of external [K+] from 0 to 10 mM while channels were activated produced no change in current magnitude (outer vestibule conformation did not change). When channels were subsequently closed and reopened in the presence of elevated [K+], current magnitude was increased (outer vestibule conformation had changed). When channels were activated in the presence of low internal [K+], or when K+ flow into conducting channels was transiently interrupted by an internal channel blocker, increasing external [K+] during activation did increase current magnitude (channel conformation did change). These data indicate that, when channels are in the activated state under physiological conditions, the outer vestibule conformation remains fixed despite changes in external [K+]. In contrast, when channel occupancy is lowered, (by channel closing, an internal blocker or low internal [K+]), the outer vestibule can interconvert between the two conformations. We discuss evidence that the ability of the outer vestibule conformation to change is regulated by the occupancy of a nonselectivity filter site by K+. Independent of the outer vestibule-based potentiation mechanism, Kv2.1 was remarkably insensitive to K+-dependent processes that influence current magnitude (current magnitude changed by <7% at membrane potentials between −20 and 30 mV). Replacement of two outer vestibule lysines in Kv2.1 by smaller neutral amino acids made current magnitude dramatically more sensitive to the reduction in K+ driving force (current magnitude changed by as much as 40%). When combined, these outer vestibule properties (fixed conformation during activation and the presence of lysines) all but prevent variation in Kv2.1 current magnitude when [K+] changes during activation. Moreover, the insensitivity of Kv2.1 current magnitude to changes in K+ driving force promotes a more uniform modulation of current over a wide range of membrane potentials by the K+-dependent regulation of outer vestibule conformation.
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DOI：
10.1085/jgp.112.6.665
发表时间：
1998-12
期刊：
The Journal of general physiology
影响因子：
--
作者：
Yang Y;Sigworth FJ
通讯作者：
Sigworth FJ
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
3.8
作者：
Holmgren, M;Smith, PL;Yellen, G
通讯作者：
Yellen, G
DOI：
10.1085/jgp.115.4.509
发表时间：
2000-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
Immke D;Korn SJ
通讯作者：
Korn SJ
影响因子：
3.4
作者：
Xiong, ZQ;Stringer, JL
通讯作者：
Stringer, JL