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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1999-6-22
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pubmed:abstractText |
1. Using whole-cell patch-clamping and Sf-9 cells expressing the rat skeletal muscle chloride channel, rCIC-1, the cellular mechanism responsible for the myotonic side effects of clofibrate derivatives was examined. 2. RS-(+/-) 2-(4-chlorophenoxy)propionic acid (RS-(+/-) CPP) and its S-(-) enantiomer produced pronounced effects on CIC-1 gating. Both compounds caused the channels to deactivate more rapidly at hyperpolarizing potentials, which showed as a decrease in the time constants of both the fast and slow deactivating components of the whole cell currents. Both compounds also produced a concentration-dependent shift in the voltage dependence of channel apparent open probability to more depolarizing potentials, with an EC50 of 0.79 and 0.21 mM for the racemate and S-(-) enantiomer respectively. R-(+) CPP at similar concentrations had no effect on gating. RS-(+/-) CPP did not block the passage of Cl- through the pore of rCIC-1. 3. CIC-1 is gated by Cl- binding to a site within an access channel and S-(-) CPP alters gating of the channel by decreasing the affinity of this binding site for Cl-. Comparison of the EC50 for RS-(+/-) CPP and S-(-) CPP indicates that R-(+) CPP can compete with the S-(-) enantiomer for the site but that it is without biological activity. 4. RS-(+/-) CPP produced the same effect on rCIC-1 gating when added to the interior of the cell and in the extracellular solution. 5. S-(-) CPP modulates the gating of CIC-1 to decrease the membrane Cl- conductance (GCl), which would account for the myotonic side effects of clofibrate and its derivatives.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-1220706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-1309879,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-1311421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-1312862,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-1659664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-1714780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-2441051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-2463645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-2579683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-457859,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-5073673,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-5316641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-5536254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-6134423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-7447955,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-7845466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-8130334,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-833760,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-8639692,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-894246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-8961185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-9192307,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-9565403,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10217531-9575303
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0007-1188
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
126
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1375-82
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10217531-2-Methyl-4-chlorophenoxyacetic Acid,
pubmed-meshheading:10217531-Animals,
pubmed-meshheading:10217531-Cell Line,
pubmed-meshheading:10217531-Chloride Channels,
pubmed-meshheading:10217531-Chlorides,
pubmed-meshheading:10217531-Dose-Response Relationship, Drug,
pubmed-meshheading:10217531-Electric Stimulation,
pubmed-meshheading:10217531-Hydrogen-Ion Concentration,
pubmed-meshheading:10217531-Ion Channel Gating,
pubmed-meshheading:10217531-Membrane Potentials,
pubmed-meshheading:10217531-Muscle Proteins,
pubmed-meshheading:10217531-Patch-Clamp Techniques,
pubmed-meshheading:10217531-Rats,
pubmed-meshheading:10217531-Stereoisomerism
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pubmed:year |
1999
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pubmed:articleTitle |
Modulation of the gating of CIC-1 by S-(-) 2-(4-chlorophenoxy) propionic acid.
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pubmed:affiliation |
Department of Physiology, University of Adelaide, South Australia, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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