help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published as Biophys J. BioFAST on April 29, 2005.
doi:10.1529/biophysj.104.053447
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
biophysj.104.053447v1
89/1/179    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bisset, D.
Right arrow Articles by Chung, S.-H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bisset, D.
Right arrow Articles by Chung, S.-H.
Biophysical Journal 89:179-186 (2005)
© 2005 The Biophysical Society

The Fast Gating Mechanism in ClC-0 Channels

David Bisset *, Ben Corry {dagger} and Shin-Ho Chung *

* Department of Theoretical Physics, Research School of Physical Sciences, The Australian National University, Canberra, Australia; and {dagger} Department of Chemistry, School of Biomedical and Chemical Sciences, The University of Western Australia, Crawley, Australia

Correspondence: Address reprint requests to Ben Corry, Fax: 61-8-6488-1005; E-mail: ben{at}theochem.uwa.edu.au.

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.




This article has been cited by other articles:


Home page
 JGPHome page
G. Zifarelli, A. R. Murgia, P. Soliani, and M. Pusch
Intracellular Proton Regulation of ClC-0
J. Gen. Physiol., July 1, 2008; 132(1): 185 - 198.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
T.-Y. Chen and T.-C. Hwang
CLC-0 and CFTR: Chloride Channels Evolved From Transporters
Physiol Rev, April 1, 2008; 88(2): 351 - 387.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
A. M. Engh, J. D. Faraldo-Gomez, and M. Maduke
The Mechanism of Fast-Gate Opening in ClC-0
J. Gen. Physiol., September 24, 2007; 130(4): 335 - 349.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
L. He, J. Denton, K. Nehrke, and K. Strange
Carboxy Terminus Splice Variation Alters ClC Channel Gating and Extracellular Cysteine Reactivity
Biophys. J., May 15, 2006; 90(10): 3570 - 3581.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
S. Traverso, G. Zifarelli, R. Aiello, and M. Pusch
Proton Sensing of CLC-0 Mutant E166D
J. Gen. Physiol., December 27, 2005; 127(1): 51 - 66.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the Biophysical Society.