Department of Neurosciences Biomedicine and Movement Sciences, Section of Physiology and Psychology, University of Verona, Verona, Italy.
National Institute of Neuroscience, Verona, Italy.
Eur J Neurosci. 2018 Jun;47(12):1474-1481. doi: 10.1111/ejn.14020. Epub 2018 Jun 26.
Evoked electrical muscle activity suppresses the transcription of mRNAs for acetylcholine receptors in extrajunctional myonuclei. Muscle denervation or disuse releases such inhibition and extrajunctional receptors appear. However, in soleus muscles paralysed with nerve-applied tetrodotoxin, a restricted perijunctional region has been described where myonuclei remain inhibited, a finding attributed to nerve-derived trophic factor(s). Here, we reinvestigate extrajunctional acetylcholine receptor expression in soleus and extensor digitorum longus muscles up to 90 days after denervation or up to 20 days of disuse, to clarify the role of trophic factors, if any. The perijunctional region of soleus muscles strongly expressed acetylcholine receptors during the first 2-3 weeks of denervation. After 2-3 months, this expression had disappeared. No perijunctional expression was seen after paralysis by tetrodotoxin or botulinum toxin A. In contrast, the extensor digitorum longus never displayed suppressed perijunctional acetylcholine receptor expression after any treatment, suggesting that it is an intrinsic property of soleus muscles. Soleus denervation only transiently removed the suppression, and its presence in long-term denervated soleus muscles contradicts any contribution from nerve-derived trophic factor(s). In conclusion, our results confirm that evoked electrical activity is the physiological factor controlling the expression of acetylcholine receptors in the entire extrajunctional membrane of skeletal muscles.
诱发的电肌肉活动抑制了神经肌肉接头外肌细胞核中乙酰胆碱受体的转录。肌肉失神经或废用会释放这种抑制，从而出现神经肌肉接头外受体。然而，在应用神经毒素四氢巴豆碱麻痹的比目鱼肌中，已经描述了一个局限的神经肌肉接头周围区域，其中肌细胞核仍然受到抑制，这一发现归因于神经源性营养因子。在这里，我们重新研究了失神经或废用 20 天后，比目鱼肌和趾长伸肌中的神经肌肉接头外乙酰胆碱受体表达，以阐明营养因子的作用（如果有的话）。在失神经后的前 2-3 周内，比目鱼肌的神经肌肉接头周围区域强烈表达乙酰胆碱受体。2-3 个月后，这种表达消失了。在四氢巴豆碱或肉毒杆菌毒素 A 麻痹后，没有观察到神经肌肉接头外表达。相比之下，伸趾长肌在任何治疗后都从未显示出受抑制的神经肌肉接头外乙酰胆碱受体表达，这表明这是比目鱼肌的固有特性。比目鱼肌失神经仅短暂地消除了抑制，而在长期失神经的比目鱼肌中存在这种抑制，与任何神经源性营养因子无关。总之，我们的结果证实，诱发的电活动是控制骨骼肌整个神经肌肉接头外膜乙酰胆碱受体表达的生理因素。
