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Figure 15. Ion displacement models for channel block. (A) Minimal three-state ion displacement model for voltage-dependent block. The transmembrane voltage drops exclusively across the narrow part of the pore that can only be occupied by permeant ions. The number of permeant ions in the selectivity filter is inconsequential to the model, and the number of ions in the inner pore is set at the minimum of one. The channel can exist in two nonblocked states with (ChNa) or without (Ch) a permeant Na+ ion at the inner pore site (internal to the narrow selectivity filter) and one blocked state (ChB). The upper blocking transition is voltage independent as the blocker binds in the empty inner pore with equilibrium constant KB, whereas the lower transition (equilibrium constant KB-Na) is voltage dependent as the blocker displaces the Na+ ion. (B) Ion displacement model with sequential blocking steps. The two leftmost nonblocked states are equivalent to those of the minimal three-state model in A, with (ChNa) and without (Ch) a Na+ ion in the inner pore. The blocker may bind (common equilibrium constant KB1) to the shallow site of either nonblocked form. It then binds at the deep binding site (ChB2). The transition that involves Na+ displacement is characterized by KB2-Na and is voltage dependent, whereas the one that does not involve Na+ displacement is characterized by KB2 and is voltage independent. Image published in: Martínez-François JR and Lu Z (2010) © 2010 Martínez-François and Lu. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license Larger Image Printer Friendly View

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