Unified modeling of conductance kinetics for low- and high-conductance potassium ion channels.
Unified modeling of conductance kinetics for low- and high-conductance potassium ion channels.
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低电导和高电导钾离子通道电导动力学的统一建模。
DOI：
10.1103/physreve.74.011902
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
C. Gray
中科院分区：
文献类型：
--
作者：
I. Tolokh;S. Goldman;C. Gray
提出了一个动力学模型来描述低电导和高电导钾离子通道的离子电导。该模型描述了通过选择性过滤器的离子渗透，这被假定为是唯一的电导确定部分的开放通道。过滤器占有率可以从零到三个离子变化，影响离子进入和离开速率。与后者的速率相比，假设过滤器内部结合位点之间的离子运动较快，从而可以对具有特定占用率的过滤器中可能的离子配置的平衡进入和退出速率常数进行平均。与一对相邻占据状态相关的平均速率常数表征特定的离子渗透机制。导出了通道电导随对称外部离子浓度变化的表达式。它包括由平衡过滤器占用概率加权的不同离子渗透机制的浓度无关电导幅度的总和。示出了每个幅度（即，每个电导机制对通道电导的最大贡献）与平均出口速率常数和表征所施加电场对速率常数和过滤器中平衡离子分布的影响的量成比例。导出的电导表达式提供了对低电导（例如，Kir2.1）和高电导（例如，KcsA）钾通道。它使人们能够获得平衡离子结合常数在不同的过滤占领和计算的平均数的离子在选择性过滤器为给定的外部离子浓度。对于KcsA，该数值（200 mM时为2.0）与可用的实验值（200 mM时为2.1）非常一致。对于高电导钾通道，选择性过滤器周围的净负电荷增加了离子结合常数，从而导致与低电导通道相比，在较小的外部离子浓度下发生较大的占据概率。这实质上增加了两个和三个离子渗透机制的贡献，与低电导通道相比，较大的电导幅度导致通道电导增加。
A kinetics model is proposed for the description of ion conductance of low- and high-conductance potassium ion channels. The model describes ion permeation through the selectivity filter, which is assumed to be the only conductance determining part of the open channel. The filter occupancy can vary from zero to three ions, affecting the ion entry and exit rates. Ion motion between the binding sites inside the filter is assumed fast compared to the latter rates allowing averaging the equilibrium entry and exit rate constants over the possible ion configurations in the filter with a particular occupancy. Averaged rate constants related to a pair of adjacent occupancy states characterize a particular ion permeation mechanism. An expression for the channel conductance as a function of the symmetrical external ion concentration is derived. It comprises a sum of concentration independent conductance amplitudes for different ion permeation mechanisms weighted by the equilibrium filter occupancy probabilities. It is shown that each amplitude (i.e., maximum contribution to the channel conductance from each conductance mechanism) is proportional to an averaged exit rate constant and to quantities characterizing the effect of the applied electric field on the rate constants and the equilibrium ion distribution in the filter. The conductance expression derived provides a good description of the experimentally observed conductance-concentration curves for low-conductance (e.g., Kir2.1) and high-conductance (e.g., KcsA) potassium channels. It enables one to obtain equilibrium ion binding constants at different filter occupancies and to calculate the average number of ions in the selectivity filter for a given external ion concentration. For KcsA this number (2.0 at 200 mM) is in a good agreement with the available experimental value (2.1 at 200 mM). For the high-conductance potassium channels the net negative electrical charge around the selectivity filter increases the ion binding constants, thereby causing the larger occupancy probabilities to occur at smaller external ion concentrations compared to the low-conductance channels. This substantially increases the contributions of the two- and three-ion permeation mechanisms, with the larger conductance amplitudes leading to increased channel conductance compared to the low-conductance channels.