Key result
An eight discrete-state model of chloride ion motion showed good agreement with a multi-ion continuous space model for computing Cl- ion permeation and fast gate closing rates.
A discrete-state model successfully replicates the complex multi-ion continuous space Brownian dynamics of ClC chloride channels, enabling more efficient computational modeling of channel behaviors.
Supports efficient ClC channel simulations; leaves open experimental validation and physiological relevance.
A discrete-state model of chloride ion motion in a ClC chloride channel is constructed, following a previously developed multi-ion continuous space model of the same system (Cheng, M. H.; Mamonov, A. B.; Dukes, J. W.; Coalson, R. D. J. Phys. Chem. B 2007, 111, 5956) that included a simplistic representation of the fast gate in this channel. The reducibility of the many-body continuous space to the eight discrete-state model considered in the present work is examined in detail by performing three-dimensional Brownian dynamics simulations of each allowed state-to-state transition in order to extract the appropriate rate constant for this process, and then inserting the pairwise rate constants thereby obtained into an appropriate set of kinetic master equations. Experimental properties of interest, including the rate of Cl(-) ion permeation through the open channel and the average rate of closing of the fast gate as a function of bulk Cl(-) ion concentrations in the intracellular and extracellular electrolyte reservoirs are computed. Good agreement is found between the results obtained via the eight discrete-state model versus the multi-ion continuous space model, thereby encouraging continued development of the discrete-state model to include more complex behaviors observed experimentally in these channels.
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Coalson et al. (2010) studied this question. Eight discrete-state model vs. Multi-ion continuous space model was evaluated on Rate of Cl(-) ion permeation through the open channel and the average rate of closing of the fast gate. An eight discrete-state model of chloride ion motion showed good agreement with a multi-ion continuous space model for computing Cl- ion permeation and fast gate closing rates.
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