Differential effects of 4-chloro-m-cresol and caffeine on skinned fibers from rat fast and slow skeletal muscles.
Contractile responses to 4-chloro-m-cresol (4-CmC) were tested in saponin- and Triton X-100-skinned fibers from soleus and edl (extensor digitorum longus) muscles of adult rats and compared with those to caffeine. The testing of different concentrations of 4-CmC on saponin-skinned fibers showed that 4-CmC induced a dose-dependent caffeine-like transient contractile response in edl and soleus due to an activation of the ryanodine receptor. Both types of skeletal muscles showed a 10 to 20 times lower 4-CmC threshold concentration and EC(50) value (concentration providing 50% of the maximal 4-CmC contracture) than for caffeine. The results indicate that edl is more sensitive than soleus to 4-CmC and that this difference in sensitivity is more marked than with caffeine. Furthermore, an increase in cytosolic Ca(2+) activity induced a more marked shift of dose-response curves toward lower concentrations for 4-CmC than caffeine. Experiments conducted on Triton X-100-skinned fibers showed that in both muscles, 4-CmC decreased in a dose-dependent manner the Ca(2+)-activated force of contractile apparatus, particularly in edl. Furthermore, the tension pCa curves indicated that 4-CmC induced a dose-dependent sensitizing (soleus) or desensitizing (edl) effect on the Ca(2+) sensitivity of myofibrils. These results indicate that edl and soleus contractile responses can be discriminated with 4-CmC instead of caffeine and that care must be taken in interpreting results because muscular pathology could be due in part to an increase in intracellular Ca(2+).
Choisy
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Laboratoire de Physiologie Générale, Centre National de la Recherche Scientifique Equipe Postulante, Faculté des Sciences et des Techniques de Nantes, France. stchoisy@yahoo.com
Huchet-Cadiou
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Léoty
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D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003285:Contractile Proteins / Q000502:physiology; D003408:Cresols / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects* / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D017830:Octoxynol; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013501:Surface-Active Agents
D003285:Contractile Proteins; D003408:Cresols; D019837:Ryanodine Receptor Calcium Release Channel; D013501:Surface-Active Agents; C006984:chlorocresol; D002110:Caffeine; D017830:Octoxynol; D002118:Calcium