title: Discrete-state representation of ion permeation coupled to fast gating in a model of ClC chloride channels: comparison to multi-ion continuous space Brownian dynamics simulations.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. coalson@pitt.edu
authors.forename: Rob D
authors.initials: RD
authors.lastname: Coalson
authors.forename: Mary Hongying
authors.initials: MH
authors.lastname: Cheng
mesh_terms: D001665:Binding Sites; D018118:Chloride Channels / Q000737:chemistry / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D015640:Ion Channel Gating; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D009068:Movement; D010539:Permeability
chemical_list: D018118:Chloride Channels; D002712:Chlorides