| Identification of three cysteines as targets for the Zn2+ blockade of the human skeletal muscle chloride channel. | |
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MedLine Citation:
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PMID: 10206982 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Currents through the human skeletal muscle chloride channel hClC-1 can be blocked by external application of 1 mM Zn2+ or the histidine-reactive compound diethyl pyrocarbonate (DEPC). The current block by Zn2+ strongly depends on the external pH (pKa near 6.9), whereas the block by DEPC is rather independent of the pH in the range of 5.5 to 8.5. To identify the target sites of these reagents, we constructed a total of twelve cysteine- and/or histidine-replacement mutants, transfected tsA201 cells with them, and investigated the resulting whole-cell chloride currents. The majority of the mutants exhibited a similar sensitivity toward Zn2+ or DEPC as wild type (WT) channels. Block by 1 mM Zn2+ was nearly absent only with the mutant C546A. Four mutants (C242A, C254A, H180A, and H451A) were slightly less sensitive to Zn2+ than WT. Tests with double, triple, and quadruple mutants yielded that, in addition to C546, C242 and C254 are also most likely participating in Zn2+-binding. |
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Authors:
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L L Kürz; H Klink; I Jakob; M Kuchenbecker; S Benz; F Lehmann-Horn; R Rüdel |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 274 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1999 Apr |
Date Detail:
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Created Date: 1999-05-20 Completed Date: 1999-05-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 11687-92 Citation Subset: IM |
Affiliation:
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Departments of General and Applied Physiology, University of Ulm, D-89069 Ulm, Germany. loathar.kuerz@medizin.uni-ulm.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Chloride Channels / antagonists & inhibitors*, genetics Cysteine / genetics, metabolism* Diethyl Pyrocarbonate / pharmacology Histidine / genetics, metabolism Humans Hydrogen-Ion Concentration Muscle Proteins / antagonists & inhibitors*, genetics Muscle, Skeletal / cytology, drug effects*, metabolism Mutagenesis, Site-Directed Zinc / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/CLC-1 channel; 0/Chloride Channels; 0/Muscle Proteins; 1609-47-8/Diethyl Pyrocarbonate; 52-90-4/Cysteine; 71-00-1/Histidine; 7440-66-6/Zinc |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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