Choisy S, Huchet-Cadiou C, Léoty C
Laboratoire de Physiologie Générale, Centre National de la Recherche Scientifique Equipe Postulante, Faculté des Sciences et des Techniques de Nantes, France.
J Pharmacol Exp Ther. 2000 Sep;294(3):884-93.
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+).
在成年大鼠比目鱼肌和趾长伸肌（EDL）经皂角苷和 Triton X - 100 处理的去皮纤维中测试了对 4 - 氯间甲酚（4 - CmC）的收缩反应，并与对咖啡因的收缩反应进行了比较。在皂角苷处理的去皮纤维上测试不同浓度的 4 - CmC 发现，由于兰尼碱受体的激活，4 - CmC 在 EDL 和比目鱼肌中诱导了剂量依赖性的类似咖啡因的瞬时收缩反应。两种类型的骨骼肌对 4 - CmC 的阈值浓度和 EC(50)值（产生最大 4 - CmC 挛缩 50%的浓度）比对咖啡因低 10 至 20 倍。结果表明，EDL 对比目鱼肌对 4 - CmC 更敏感，且这种敏感性差异比对咖啡因时更明显。此外，胞质 Ca(2+)活性的增加使 4 - CmC 的剂量反应曲线比咖啡因更明显地向较低浓度偏移。在 Triton X - 100 处理的去皮纤维上进行的实验表明，在两种肌肉中，4 - CmC 均以剂量依赖性方式降低收缩装置的 Ca(2+)激活力，尤其是在 EDL 中。此外，张力 - pCa 曲线表明，4 - CmC 对肌原纤维的 Ca(2+)敏感性诱导了剂量依赖性的增敏（比目鱼肌）或脱敏（EDL）效应。这些结果表明，可用 4 - CmC 而非咖啡因来区分 EDL 和比目鱼肌的收缩反应，并且在解释结果时必须谨慎，因为肌肉病理可能部分归因于细胞内 Ca(2+)的增加。
