Germinario E, Esposito A, Megighian A, Midrio M, Betto R, Danieli-Betto D
Department of Human Anatomy and Physiology, University of Padova, 35131 Padova, Italy.
J Appl Physiol (1985). 2004 Feb;96(2):645-9. doi: 10.1152/japplphysiol.00481.2003.
The reduced release of Ca2+ from sarcoplasmic reticulum (SR) is considered a major determinant of muscle fatigue. In the present study, we investigated whether the presence of dantrolene, an established inhibitor of SR Ca2+ release, or caffeine, a drug facilitating SR Ca2+ release, modifies muscle fatigue development. Accordingly, the effects of Ca2+ release modulators were analyzed in vitro in mouse fast-twitch [extensor digitorum longus (EDL)] and slow-twitch (soleus) muscles, fatigued by repeated short tetani (40 Hz for 300 ms, 0.5 s(-1) in soleus and 60 Hz for 300 ms, 0.3 s(-1) in EDL, for 6 min). Caffeine produced a substantial increase of tetanic tension of both EDL and soleus muscles, whereas dantrolene decreased tetanic tension only in EDL muscle. In both EDL and soleus muscles, 5 microM dantrolene did not affect fatigue development, whereas 20 microM dantrolene produced a positive staircase during the first 3 min of stimulation in EDL muscle and a slowing of fatigue development in soleus muscle. The development of the positive staircase was abolished by the addition of 15 microM ML-7, a selective inhibitor of myosin light chain kinase. On the other hand, caffeine caused a larger and faster loss of tension in both EDL and soleus muscles. The results seem to indicate that the changes in fatigue profile induced by caffeine or dantrolene are mainly due to the changes in the initial tetanic tension caused by the drugs, with the resulting changes in the level of contraction-dependent factors of fatigue, rather than to changes in the SR Ca2+ release during fatigue development.
肌浆网（SR）中Ca2+释放减少被认为是肌肉疲劳的主要决定因素。在本研究中，我们调查了丹曲林（一种已确定的SR Ca2+释放抑制剂）或咖啡因（一种促进SR Ca2+释放的药物）的存在是否会改变肌肉疲劳的发展。因此，在体外分析了Ca2+释放调节剂对小鼠快肌[趾长伸肌（EDL）]和慢肌（比目鱼肌）的影响，这些肌肉通过重复短强直刺激（40 Hz，持续300 ms，比目鱼肌为0.5 s(-1)，EDL为60 Hz，持续300 ms，0.3 s(-1)，持续6分钟）而疲劳。咖啡因使EDL和比目鱼肌的强直张力大幅增加，而丹曲林仅使EDL肌肉的强直张力降低。在EDL和比目鱼肌中，5 microM丹曲林不影响疲劳发展，而20 microM丹曲林在EDL肌肉刺激的前3分钟产生正阶梯现象，并使比目鱼肌的疲劳发展减慢。加入15 microM ML-7（肌球蛋白轻链激酶的选择性抑制剂）后，正阶梯现象消失。另一方面，咖啡因使EDL和比目鱼肌的张力损失更大且更快。结果似乎表明，咖啡因或丹曲林引起的疲劳特征变化主要是由于药物引起的初始强直张力变化，以及由此导致的疲劳收缩相关因素水平的变化，而不是由于疲劳发展过程中SR Ca2+释放的变化。
