Ionic selectivity in L-type calcium channels by electrostatics and hard-core repulsion.
Ionic selectivity in L-type calcium channels by electrostatics and hard-core repulsion.
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DOI：
10.1085/jgp.200910211
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Nonner W
中科院分区：
文献类型：
--
作者：
Boda D;Valiskó M;Henderson D;Eisenberg B;Gillespie D;Nonner W
构建了L型钙通道选择性离子结合的物理模型，并将模型结果与实验数据进行了比较。这种简化模型只处理离子和羧酸氧的EEEE轨迹明确和限制的相互作用，以硬核排斥和离子-离子和离子-介电静电力。结构原子提供了一个灵活的环境，通过阳离子，从而导致在一个自组织的诱导适合模型的选择性过滤器。实验条件涉及的二元混合物的碱金属和/或碱土金属离子的计算使用平衡蒙特卡罗模拟在巨正则系综。该模型孔拒绝碱金属离子的存在下，生物浓度的Ca 2+和预测的阻断碱金属离子电流的微摩尔Ca 2+。电导模式中观察到的各种混合物含有Na+和Li+，或Ba ~（2+）和Ca ~（2+），预测。Ca 2+在阻断Na+电流方面比Ba 2+更有效。与使用缓冲的Ca 2+溶液的实验明显相反，预测的Ca 2+阻断碱金属离子电流的效力取决于碱金属离子的种类和浓度，如所预期的，如果这些离子与Ca 2+竞争孔。这些实验依赖于在不同背景的散装盐中缓冲的Ca 2+和pH值的溶液中的Ca 2+活性的有问题的估计。模拟的Ca 2+分布与模型孔沐浴在含有不同量的Li+的解决方案揭示了一个“障碍和良好”的模式。钙离子的进入/退出势垒强烈调制的锂离子浓度的浴，这表明所观察到的动力学现象的物理解释。我们的模拟结果表明，L-型钙通道的选择性可以从离子和几个关键的通道原子之间的静电和硬核排斥力的相互作用而产生。还原系统选择以最小离子体积提供最大电荷的阳离子。
A physical model of selective “ion binding” in the L-type calcium channel is constructed, and consequences of the model are compared with experimental data. This reduced model treats only ions and the carboxylate oxygens of the EEEE locus explicitly and restricts interactions to hard-core repulsion and ion–ion and ion–dielectric electrostatic forces. The structural atoms provide a flexible environment for passing cations, thus resulting in a self-organized induced-fit model of the selectivity filter. Experimental conditions involving binary mixtures of alkali and/or alkaline earth metal ions are computed using equilibrium Monte Carlo simulations in the grand canonical ensemble. The model pore rejects alkali metal ions in the presence of biological concentrations of Ca2+ and predicts the blockade of alkali metal ion currents by micromolar Ca2+. Conductance patterns observed in varied mixtures containing Na+ and Li+, or Ba2+ and Ca2+, are predicted. Ca2+ is substantially more potent in blocking Na+ current than Ba2+. In apparent contrast to experiments using buffered Ca2+ solutions, the predicted potency of Ca2+ in blocking alkali metal ion currents depends on the species and concentration of the alkali metal ion, as is expected if these ions compete with Ca2+ for the pore. These experiments depend on the problematic estimation of Ca2+ activity in solutions buffered for Ca2+ and pH in a varying background of bulk salt. Simulations of Ca2+ distribution with the model pore bathed in solutions containing a varied amount of Li+ reveal a “barrier and well” pattern. The entry/exit barrier for Ca2+ is strongly modulated by the Li+ concentration of the bath, suggesting a physical explanation for observed kinetic phenomena. Our simulations show that the selectivity of L-type calcium channels can arise from an interplay of electrostatic and hard-core repulsion forces among ions and a few crucial channel atoms. The reduced system selects for the cation that delivers the largest charge in the smallest ion volume.
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DOI：
10.1085/jgp.88.3.293
发表时间：
1986-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Hess P;Lansman JB;Tsien RW
通讯作者：
Tsien RW
DOI：
10.1073/pnas.86.13.5207
发表时间：
1989-07-01
影响因子：
11.1
作者：
FRIEL, DD;TSIEN, RW
通讯作者：
TSIEN, RW
影响因子：
16.2
作者：
ELLINOR, PT;YANG, J;TSIEN, RW
通讯作者：
TSIEN, RW
影响因子：
5.5
作者：
ALMERS, W;MCCLESKEY, EW;PALADE, PT
通讯作者：
PALADE, PT
影响因子：
3.4
作者：
Boda, Dezso;Nonner, Wolfgang;Gillespie, Dirk
通讯作者：
Gillespie, Dirk