TY - JOUR T1 - Differential Effects of 4-Chloro-<em>m</em>-cresol and Caffeine on Skinned Fibers from Rat Fast and Slow Skeletal Muscles JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 884 LP - 893 VL - 294 IS - 3 AU - Stéphanie Choisy AU - Corinne Huchet-Cadiou AU - Claude Léoty Y1 - 2000/09/01 UR - http://jpet.aspetjournals.org/content/294/3/884.abstract N2 - 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 EC50 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 Ca2+ 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 Ca2+-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 Ca2+ 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 Ca2+. The American Society for Pharmacology and Experimental Therapeutics ER -