Connold A L, Vrbová G
Department of Anatomy and Developmental Biology, University College London, U.K.
Neuroscience. 1994 Nov;63(1):327-38. doi: 10.1016/0306-4522(94)90027-2.
In the soleus muscle of the rat following section of the L5 ventral ramus (partial denervation) the remaining motor axons increase their territory by sprouting. Nerve sprouts are first seen two to three days after the operation, their number peaks at 10-14 days and subsequently remains at this level. The time course of the initial sprouting in partially denervated muscles is not altered by paralysing the muscles with alpha-bungarotoxin, and the initial extent of the sprouting is, if anything, greater in the paralysed muscles. However, unlike in controls, this level of sprouting is not maintained and neuromuscular contacts are lost when muscles recover from the paralysis. The loss of these contacts can be prevented by treatment of these partially denervated paralysed muscles with leupeptin, an inhibitor of calcium-activated neutral protease. Interestingly, more contacts are rescued when leupeptin is applied 10 days after alpha-bungarotoxin treatment, when sprouting has reached high levels, than at three days, when sprouting has just begun. The neuromuscular connections rescued by leupeptin are functional. Maximum tetanic tension produced by untreated soleus muscles two to five months after partial denervation is 66 +/- 9% of contralateral control muscles, but only 39 +/- 8% when the muscles were paralysed with alpha-bungarotoxin for 12-14 days after partial denervation. However, when partially denervated paralysed muscles were treated with leupeptin three and 10 days after alpha-bungarotoxin treatment their tension output is 74 +/- 3% and 81 +/- 8%, respectively. After partial denervation alone, motor units are twice their normal size. Short-term paralysis with alpha-bungarotoxin prevents this increase in motor unit territory. However, the application of leupeptin to the paralysed muscles rescues neuromuscular contacts, allowing motor unit size to remain expanded, at around 2-2.5-fold. Thus, following recovery from temporary paralysis with alpha-bungarotoxin, there is a sudden withdrawal of neuromuscular contacts and these can be rescued by treatment with leupeptin.
在大鼠的比目鱼肌中，切断L5腹侧支（部分去神经支配）后，剩余的运动轴突通过发芽来扩大其支配区域。神经芽在手术后两到三天首次出现，其数量在10 - 14天达到峰值，随后保持在该水平。用α - 银环蛇毒素使肌肉麻痹，并不会改变部分去神经支配肌肉中初始发芽的时间进程，而且在麻痹的肌肉中，初始发芽程度甚至更大。然而，与对照组不同的是，这种发芽水平无法维持，当肌肉从麻痹状态恢复时，神经肌肉接触会丧失。用钙激活中性蛋白酶抑制剂亮抑酶肽处理这些部分去神经支配的麻痹肌肉，可以防止这些接触的丧失。有趣的是，在α - 银环蛇毒素处理10天后（此时发芽已达到高水平）应用亮抑酶肽，比在处理3天后（此时发芽刚刚开始）应用亮抑酶肽能挽救更多的接触。亮抑酶肽挽救的神经肌肉连接是有功能的。部分去神经支配两到五个月后，未处理的比目鱼肌产生的最大强直张力是对侧对照肌肉的66±9%，但在部分去神经支配后用α - 银环蛇毒素麻痹肌肉12 - 14天，最大强直张力仅为39±8%。然而，在α - 银环蛇毒素处理后三天和十天，用亮抑酶肽处理部分去神经支配的麻痹肌肉，其张力输出分别为74±3%和81±8%。单独部分去神经支配后，运动单位大小是正常大小的两倍。用α - 银环蛇毒素进行短期麻痹可防止运动单位支配区域的这种增加。然而，将亮抑酶肽应用于麻痹的肌肉可挽救神经肌肉接触，使运动单位大小保持扩大，约为正常大小的2 - 2.5倍。因此，在用α - 银环蛇毒素暂时麻痹后恢复时，会突然出现神经肌肉接触的减少，而用亮抑酶肽处理可以挽救这些接触。
