Low resistance, large dimension entrance to the inner cavity of BK channels determined by changing side-chain volume.
Low resistance, large dimension entrance to the inner cavity of BK channels determined by changing side-chain volume.
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DOI：
10.1085/jgp.201110616
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Magleby KL
中科院分区：
文献类型：
--
作者：
Geng Y;Niu X;Magleby KL
大电导Ca2+和电压激活的K+ (BK)通道具有所有K+选择性通道中最大的电导（250-300 pS）。然而，离子传导途径的各个部分对电导的贡献尚不清楚。在这里，我们研究了内腔入口对大电导的贡献。四个α亚基的E321/E324残基环绕着内腔的入口。为了确定321/324是否可以通过内部传导途径进入，我们测量了暴露和洗涤硫醇试剂到E321C和E324C通道胞内侧前后的单通道电流幅度。MPA−增加电流，MTSET+减少电流，321位和324位之间没有差异，这表明321/324位侧链可以从内部传导途径进入，并且对电导具有相同的影响。对于中性氨基酸，通过在321/324位置取代大侧链氨基酸来减小内腔入口的尺寸可以降低向外的单通道电导，而用较小的侧链取代来增加入口的尺寸则没有什么效果。向外电导的降低被高[K+]i所抵消。取代对内部电导影响不大。用一个可变电阻和一个固定电阻串联的模型拟合电导与侧链体积的关系图表明，野生型通道内腔入口的有效直径和长度分别为17.7和5.6 Å，入口电阻占传导途径总电阻的7%。估计的尺寸与MthK的结构一致，MthK是一种与BK通道同源的古细菌。我们的观察表明，BK通道具有低电阻，大的内腔入口，入口的大小是必要的，不限制电流，但不是太大。
Large-conductance Ca2+- and voltage-activated K+ (BK) channels have the largest conductance (250–300 pS) of all K+-selective channels. Yet, the contributions of the various parts of the ion conduction pathway to the conductance are not known. Here, we examine the contribution of the entrance to the inner cavity to the large conductance. Residues at E321/E324 on each of the four α subunits encircle the entrance to the inner cavity. To determine if 321/324 is accessible from the inner conduction pathway, we measured single-channel current amplitudes before and after exposure and wash of thiol reagents to the intracellular side of E321C and E324C channels. MPA− increased currents and MTSET+ decreased currents, with no difference between positions 321 and 324, indicating that side chains at 321/324 are accessible from the inner conduction pathway and have equivalent effects on conductance. For neutral amino acids, decreasing the size of the entrance to the inner cavity by substituting large side-chain amino acids at 321/324 decreased outward single-channel conductance, whereas increasing the size of the entrance with smaller side-chain substitutions had little effect. Reductions in outward conductance were negated by high [K+]i. Substitutions had little effect on inward conductance. Fitting plots of conductance versus side-chain volume with a model consisting of one variable and one fixed resistor in series indicated an effective diameter and length of the entrance to the inner cavity for wild-type channels of 17.7 and 5.6 Å, respectively, with the resistance of the entrance ∼7% of the total resistance of the conduction pathway. The estimated dimensions are consistent with the structure of MthK, an archaeal homologue to BK channels. Our observations suggest that BK channels have a low resistance, large entrance to the inner cavity, with the entrance being as large as necessary to not limit current, but not much larger.
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影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
5.5
作者：
Houamed, Khaled M.;Sweet, Ian R.;Satin, Leslie S.
通讯作者：
Satin, Leslie S.
DOI：
10.1007/s00249-004-0452-x
发表时间：
2005-06-01
影响因子：
2
作者：
Aguilella-Arzo, M;Aguilella, VM;Eisenberg, RS
通讯作者：
Eisenberg, RS
内向整流的分子基础：通过合并通道和配体诱变定位的多胺相互作用位点。
DOI：
10.1085/jgp.200409159
发表时间：
2004-11
期刊：
The Journal of general physiology
影响因子：
--
作者：
Kurata HT;Phillips LR;Rose T;Loussouarn G;Herlitze S;Fritzenschaft H;Enkvetchakul D;Nichols CG;Baukrowitz T
通讯作者：
Baukrowitz T
DOI：
10.1085/jgp.200509286
发表时间：
2005-08
期刊：
The Journal of general physiology
影响因子：
--
作者：
Brelidze TI;Magleby KL
通讯作者：
Magleby KL