Bray J J, Harris A J
J Physiol. 1975 Dec;253(1):53-77. doi: 10.1113/jphysiol.1975.sp011179.
Small doses of botulinum toxin can produce partial blockage of transmitter release at the nerve--muscle junction. 2. Subthreshold e.p.p.s, 3--10 days after poisoning, show a distribution of amplitudes that is fitted by Poisson statistics. Successive e.p.p.s. in a short train show a marked facilitation. 3. Two weeks or more after poisoning with a dose of toxin that paralyses the whole muscle, when nerve--muscle transmission is in course of recovery, subthreshold e.p.p.s have an amplitude distribution that is fitted by binomial statistics. This property of transmission is similar to those described in newly formed nerve--muscle junctions, during embryogenesis or regeneration. 4. Muscle fibres with subthreshold transmission in the 5--10 day group of muscles were all supersensitive to ACh, as were a number of fibres in which nerve stimulation still produced an action potential. 5. Two weeks or more after poisoning, muscle fibres with subthreshold transmission had lost their extrajunctional ACh-sensitivity, as had many fibres with m.e.p.p.s of roughly normal frequency but no response to nerve stimulation. 6. In diaphragm muscles poisoned with botulinum toxin between 1 and 4 days previously, the rate of fast axonal transport of radioactively labelled proteins down the phrenic nerve is not greatly affected, but the amount of materials carried is reduced to about one quarter of normal. These labelled proteins accumulate in the intramuscular portion of the phrenic nerve, in or near the nerve terminals, to a much greater extent than in controls, showing that the normal release of some of these materials has been prevented by the toxin. 7. It is concluded that the blockage of the trophic effects of nerves by botulinum toxin is due to a blockage of release of trophic factors other than ACh. 8. The muscle nerve cannot maintain a muscle in its normal state simply by activation of contraction, and a regenerating nerve terminal can restore a muscle towards its normal state before it can release enough ACh to produce muscle contraction.
小剂量肉毒杆菌毒素可在神经 - 肌肉接头处产生递质释放的部分阻滞。2. 中毒后3 - 10天，阈下终板电位（e.p.p.s）的幅度分布符合泊松统计。短串刺激中的连续e.p.p.s显示出明显的易化作用。3. 用能使整块肌肉麻痹的剂量的毒素中毒两周或更长时间后，当神经 - 肌肉传递正在恢复时，阈下e.p.p.s的幅度分布符合二项式统计。这种传递特性类似于胚胎发育或再生过程中新形成的神经 - 肌肉接头中所描述的特性。4. 在中毒5 - 10天的肌肉组中，具有阈下传递的肌纤维对乙酰胆碱（ACh）都超敏感，许多神经刺激仍能产生动作电位的纤维也是如此。5. 中毒两周或更长时间后，具有阈下传递的肌纤维已失去其接头外ACh敏感性，许多具有大致正常频率的微小终板电位（m.e.p.p.s）但对神经刺激无反应的纤维也是如此。6. 在1 - 4天前用肉毒杆菌毒素中毒的膈肌中，放射性标记蛋白质沿膈神经的快速轴突运输速率受影响不大，但所携带的物质数量减少至正常的约四分之一。这些标记蛋白质在膈神经的肌内部分、神经末梢内或其附近积累的程度比对照组大得多，表明毒素阻止了其中一些物质的正常释放。7. 得出的结论是，肉毒杆菌毒素对神经营养作用的阻滞是由于除ACh之外的营养因子释放受阻。8. 肌肉神经不能仅通过激活收缩来使肌肉维持在正常状态，并且再生的神经末梢在释放足够的ACh以产生肌肉收缩之前就能使肌肉恢复到接近正常状态。
