The fast gating mechanism in ClC-0 channels

David Bisset, Ben Corry*, Shin Ho Chung

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    32 Citations (Scopus)

    Abstract

    We investigate and then modify the hypothesis that a glutamate side chain acts as the fast gate in ClC-0 channels. We first create a putative open-state configuration of the prokaryotic ClC Cl- channel using its crystallographic structure as a basis. Then, retaining the same pore shape, the prokaryotic ClC channel is converted to ClC-0 by replacing all the nonconserved polar and charged residues. Using this open-state channel model, we carry out molecular dynamics simulations to study how the glutamate side chain can move between open and closed configurations. When the side chain extends toward the extracellular end of the channel, it presents an electrostatic barrier to Cl- conduction. However, external Cl- ions can push the side chain into a more central position where, pressed against the channel wall, it does not impede the motion of Cl- ions. Additionally, a proton from a low-pH external solution can neutralize the extended glutamate side chain, which also removes the barrier to conduction. Finally, we use Brownian dynamics simulations to demonstrate the influence of membrane potential and external Cl- concentration on channel open probability.

    Original languageEnglish
    Pages (from-to)179-186
    Number of pages8
    JournalBiophysical Journal
    Volume89
    Issue number1
    DOIs
    Publication statusPublished - Jul 2005

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