| pubmed-article:10217531 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10217531 | lifeskim:mentions | umls-concept:C1709059 | lld:lifeskim |
| pubmed-article:10217531 | lifeskim:mentions | umls-concept:C0045721 | lld:lifeskim |
| pubmed-article:10217531 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:10217531 | pubmed:dateCreated | 1999-6-22 | lld:pubmed |
| pubmed-article:10217531 | 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. | lld:pubmed |
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| pubmed-article:10217531 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10217531 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10217531 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:10217531 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10217531 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:10217531 | pubmed:issn | 0007-1188 | lld:pubmed |
| pubmed-article:10217531 | pubmed:author | pubmed-author:RobertsM LML | lld:pubmed |
| pubmed-article:10217531 | pubmed:author | pubmed-author:BryantS HSH | lld:pubmed |
| pubmed-article:10217531 | pubmed:author | pubmed-author:BretagA HAH | lld:pubmed |
| pubmed-article:10217531 | pubmed:author | pubmed-author:AstillD SDS | lld:pubmed |
| pubmed-article:10217531 | pubmed:author | pubmed-author:RychkovG YGY | lld:pubmed |
| pubmed-article:10217531 | pubmed:author | pubmed-author:AromatarisE... | lld:pubmed |
| pubmed-article:10217531 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10217531 | pubmed:volume | 126 | lld:pubmed |
| pubmed-article:10217531 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10217531 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10217531 | pubmed:pagination | 1375-82 | lld:pubmed |
| pubmed-article:10217531 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:10217531 | pubmed:year | 1999 | lld:pubmed |
| pubmed-article:10217531 | pubmed:articleTitle | Modulation of the gating of CIC-1 by S-(-) 2-(4-chlorophenoxy) propionic acid. | lld:pubmed |
| pubmed-article:10217531 | pubmed:affiliation | Department of Physiology, University of Adelaide, South Australia, Australia. | lld:pubmed |
| pubmed-article:10217531 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10217531 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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