Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/27552
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Bennetts, B. | - |
dc.contributor.author | Rychkov, G. | - |
dc.contributor.author | Ng, H. | - |
dc.contributor.author | Morton, C. | - |
dc.contributor.author | Stapleton, D. | - |
dc.contributor.author | Parker, M. | - |
dc.contributor.author | Cromer, B. | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Journal of Biological Chemistry, 2005; 280(37):32452-32458 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.issn | 1083-351X | - |
dc.identifier.uri | http://hdl.handle.net/2440/27552 | - |
dc.description.abstract | ClC proteins are a family of chloride channels and transporters that are found in a wide variety of prokaryotic and eukaryotic cell types. The mammalian voltage-gated chloride channel ClC-1 is important for controlling the electrical excitability of skeletal muscle. Reduced excitability of muscle cells during metabolic stress can protect cells from metabolic exhaustion and is thought to be a major factor in fatigue. Here we identify a novel mechanism linking excitability to metabolic state by showing that ClC-1 channels are modulated by ATP. The high concentration of ATP in resting muscle effectively inhibits ClC-1 activity by shifting the voltage gating to more positive potentials. ADP and AMP had similar effects to ATP, but IMP had no effect, indicating that the inhibition of ClC-1 would only be relieved under anaerobic conditions such as intense muscle activity or ischemia, when depleted ATP accumulates as IMP. The resulting increase in ClC-1 activity under these conditions would reduce muscle excitability, thus contributing to fatigue. We show further that the modulation by ATP is mediated by cystathionine ß-synthase-related domains in the cytoplasmic C terminus of ClC-1. This defines a function for these domains as gating-modulatory domains sensitive to intracellular ligands, such as nucleotides, a function that is likely to be conserved in other ClC proteins. | - |
dc.description.statementofresponsibility | Brett Bennetts, Grigori Y. Rychkov, Hooi-Ling Ng, Craig J. Morton, David Stapleton, Michael W. Parker, and Brett A. Cromer | - |
dc.language.iso | en | - |
dc.publisher | Amer Soc Biochemistry Molecular Biology Inc | - |
dc.rights | © 2005 by The American Society for Biochemistry and Molecular Biology, Inc. | - |
dc.source.uri | http://www.jbc.org/cgi/content/abstract/280/37/32452 | - |
dc.subject | Muscle, Skeletal | - |
dc.subject | Cytoplasm | - |
dc.subject | Animals | - |
dc.subject | Humans | - |
dc.subject | Cystathionine beta-Synthase | - |
dc.subject | Chloride Channels | - |
dc.subject | Adenosine Diphosphate | - |
dc.subject | Adenosine Monophosphate | - |
dc.subject | Adenosine Triphosphate | - |
dc.subject | Ligands | - |
dc.subject | Mutagenesis, Site-Directed | - |
dc.subject | Immunoprecipitation | - |
dc.subject | Ion Channel Gating | - |
dc.subject | Amino Acid Sequence | - |
dc.subject | Protein Structure, Tertiary | - |
dc.subject | Protein Binding | - |
dc.subject | Sequence Homology, Amino Acid | - |
dc.subject | Dose-Response Relationship, Drug | - |
dc.subject | Mutation | - |
dc.subject | Models, Molecular | - |
dc.subject | Software | - |
dc.subject | Molecular Sequence Data | - |
dc.title | Cytoplasmic ATP-sensing domains regulate gating of skeletal muscle ClC-1 chloride channels | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1074/jbc.M502890200 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Rychkov, G. [0000-0002-2788-2977] | - |
Appears in Collections: | Aurora harvest 6 Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.