A three-state, multiion kinetic model was proposed to enable the conduction properties of the mammalian channel CIC-O 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 CIC-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 CIC-0. It provides a starting point for experimentalists to test the three-state model, and would help in understanding the conduction mechanism of CIC-0.
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