Ion-Ion interactions at the selectivity filter. Evidence from K(+)-dependent modulation of tetraethylammonium efficacy in Kv2.1 potassium channels.
Ion-Ion interactions at the selectivity filter. Evidence from K(+)-dependent modulation of tetraethylammonium efficacy in Kv2.1 potassium channels.
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DOI：
10.1085/jgp.115.4.509
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发表时间：
2000-04
期刊：
影响因子：
--
通讯作者：
Korn SJ
中科院分区：
文献类型：
--
作者：
Immke D;Korn SJ
在Kv2.1钾通道中，K+与选择性过滤器相关的高亲和力位点的结合调节通道对外部TEA的敏感性。在携带Na+电流的通道中，浓度≤30 μM的K+与TEA调节位点相互作用。在本文中，我们进一步的TEA调制网站的特点，并研究如何改变K+的孔占用影响的K+与该网站的相互作用。在高的内部和外部[K+]存在下，TEA以1.9 ± 0.2 mM的IC 50阻断100%的电流。在不存在替代渗透离子（如Na+）的情况下，减少K+进入孔导致TEA功效降低，但对TEA效力产生很少或没有变化（在TEA的最大阻断仅为32%的条件下，阻断的IC 50为2.0 ± 0.6 mM）。TEA阻断的全或无性质（通道完全敏感或完全不敏感）表明，一个选择性过滤器结合位点必须被TEA敏感性占据，并且一个选择性过滤器结合位点不参与调节TEA敏感性。在三个不同水平的K+占用率下，通过操纵内部K+进入孔来实现，外部[K+]的升高使通道从TEA不敏感状态转变为敏感状态，EC 50为100 mM。结合先前的结果，这些数据表明，当孔中只有一个K+时，TEA调节位点对K+具有高亲和力，当孔隙已经被K+占据时。这些结果表明，离子-离子相互作用发生在选择性过滤器。这些结果还表明，选择性过滤器是外部K+的至少一个低亲和力调节作用的网站，并且选择性过滤器K+结合位点在功能上不可互换。
In the Kv2.1 potassium channel, binding of K+ to a high-affinity site associated with the selectivity filter modulates channel sensitivity to external TEA. In channels carrying Na+ current, K+ interacts with the TEA modulation site at concentrations ≤30 μM. In this paper, we further characterized the TEA modulation site and examined how varying K+ occupancy of the pore influenced the interaction of K+ with this site. In the presence of high internal and external [K+], TEA blocked 100% of current with an IC50 of 1.9 ± 0.2 mM. In the absence of a substitute permeating ion, such as Na+, reducing access of K+ to the pore resulted in a reduction of TEA efficacy, but produced little or no change in TEA potency (under conditions in which maximal block by TEA was just 32%, the IC50 for block was 2.0 ± 0.6 mM). The all-or-none nature of TEA block (channels were either completely sensitive or completely insensitive), indicated that one selectivity filter binding site must be occupied for TEA sensitivity, and that one selectivity filter binding site is not involved in modulating TEA sensitivity. At three different levels of K+ occupancy, achieved by manipulating access of internal K+ to the pore, elevation of external [K+] shifted channels from a TEA-insensitive to -sensitive state with an EC50 of ∼10 mM. Combined with previous results, these data demonstrate that the TEA modulation site has a high affinity for K+ when only one K+ is in the pore and a low affinity for K+ when the pore is already occupied by K+. These results indicate that ion–ion interactions occur at the selectivity filter. These results also suggest that the selectivity filter is the site of at least one low affinity modulatory effect of external K+, and that the selectivity filter K+ binding sites are not functionally interchangeable.
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DOI：
10.1085/jgp.111.2.195
发表时间：
1998-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Kiss L;Immke D;LoTurco J;Korn SJ
通讯作者：
Korn SJ
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
56.9
作者：
Baukrowitz, T;Yellen, G
通讯作者：
Yellen, G
影响因子：
16.2
作者：
NEWLAND, CF;ADELMAN, JP;ALMERS, W
通讯作者：
ALMERS, W
DOI：
10.1073/pnas.89.6.2466
发表时间：
1992-03-15
影响因子：
11.1
作者：
PARDO, LA;HEINEMANN, SH;STUHMER, W
通讯作者：
STUHMER, W