Modeling the fast gating mechanism in the ClC-0 chloride channel. 2007

Mary H Cheng, and Artem B Mamonov, and J Warren Dukes, and Rob D Coalson
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

A simplified three-dimensional model ClC-0 chloride channel is constructed to couple the permeation of Cl- ions to the motion of a glutamate side chain that acts as the putative fast gate in the ClC-0 channel. The gate is treated as a single spherical particle attached by a rod to a pivot point. This particle moves in a one-dimensional arc under the influence of a bistable potential, which mimics the isomerization process by which the glutamate side chain moves from an open state (not blocking the channel pore) to a closed state (blocking the channel pore, at a position which also acts as a binding site for Cl- ions moving through the channel). A dynamic Monte Carlo (DMC) technique is utilized to perform Brownian dynamics simulations to investigate the dependence of the gate closing rate on both internal and external chloride concentration and the gate charge as well. To accelerate the simulation of gate closing to a time scale that can be accommodated with current methodology and computer power, namely, microseconds, parameters that govern the motion of the bare gate (i.e., in the absence of coupling to the permeating ions) are chosen appropriately. Our simulation results are in qualitative agreement with experimental observations and consistent with the "foot-in-the-door" mechanism (Chen et al. J. Gen. Physiol. 2003, 122, 641; Chen and Miller J. Gen. Physiol. 1996, 108, 237), although the absolute time scale of gate closing in the real channel is much longer (millisecond time scale). A simple model based on the fractional occupation probability of the Cl- binding site that is ultimately blocked by the fast gate suggests straightforward scalability of simulation results for the model channel considered herein to experimentally realistic time scales.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009010 Monte Carlo Method In statistics, a technique for numerically approximating the solution of a mathematical problem by studying the distribution of some random variable, often generated by a computer. The name alludes to the randomness characteristic of the games of chance played at the gambling casinos in Monte Carlo. (From Random House Unabridged Dictionary, 2d ed, 1993) Method, Monte Carlo
D013816 Thermodynamics A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed) Thermodynamic
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D015640 Ion Channel Gating The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability. Gating, Ion Channel,Gatings, Ion Channel,Ion Channel Gatings
D018118 Chloride Channels Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN. CaCC,Calcium-Activated Chloride Channel,Chloride Ion Channel,Chlorine Channel,Ion Channels, Chloride,CaCCs,Calcium-Activated Chloride Channels,Chloride Channel,Chloride Ion Channels,Chlorine Channels,Ion Channel, Chloride,Calcium Activated Chloride Channel,Calcium Activated Chloride Channels,Channel, Calcium-Activated Chloride,Channel, Chloride,Channel, Chloride Ion,Channel, Chlorine,Channels, Calcium-Activated Chloride,Channels, Chloride,Channels, Chloride Ion,Channels, Chlorine,Chloride Channel, Calcium-Activated,Chloride Channels, Calcium-Activated

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