A three-state, multiion kinetic model was proposed to enable the conduction properties of the mammalian channel ClC-0 to be well characterized. Using this rate-theory based model, the current-voltage and conductance-concentration relations were obtained. The five parameters needed were determined by fitting the data of conduction experiments of the wild-type ClC-0 and its K519C mutant. The model was then tested against available calculation and simulation data, and the energy differences between distinct chloride-occupancy states computed agreed with an independent calculation on the binding free energies solved by using the Poisson-Boltzmann equation. The average ion number of conduction and the ion passing duration calculated closely resembled the values obtained from Brownian dynamics simulations. According to the model, the decrease of conductance caused by mutating residue K519 to C519 can be attributed to the effect of K519C mutation on translocation rate constants. Our study sets up a theoretical model for ion permeation and conductance in ClC-0. It provides a starting point for experimentalists to test the three-state model, and would help in understanding the conduction mechanism of ClC-0.

中文翻译：

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ClC-0 氯离子通道传导特性的三态多离子动力学模型

提出了一种三态多离子动力学模型，以便能够很好地表征哺乳动物通道 ClC-0 的传导特性。使用这种基于速率理论的模型，可以获得电流-电压和电导-浓度关系。所需的五个参数是通过拟合野生型 ClC-0 及其 K519C 突变体的传导实验数据来确定的。然后根据可用的计算和模拟数据测试模型，计算出的不同氯化物占据状态之间的能量差异与使用泊松-玻尔兹曼方程求解的结合自由能的独立计算一致。计算的平均传导离子数和离子通过持续时间与从布朗动力学模拟获得的值非常相似。根据模型，将残基 K519 突变为 C519 引起的电导降低可归因于 K519C 突变对易位速率常数的影响。我们的研究为 ClC-0 中的离子渗透和电导建立了理论模型。它为实验者测试三态模型提供了一个起点，并有助于理解 ClC-0 的传导机制。