Plomp J J, Van Kempen G T, De Baets M B, Graus Y M, Kuks J B, Molenaar P C
Department of Physiology, University of Leiden, Netherlands.
Ann Neurol. 1995 May;37(5):627-36. doi: 10.1002/ana.410370513.
In myasthenia gravis, loss of acetylcholine receptors at motor end-plates is induced by antireceptor autoantibodies. At end-plates in rats in which myasthenia gravis-like symptoms are induced by chronic treatment with alpha-bungarotoxin, acetylcholine release is increased. Within muscles from such rats there is a strong correlation between the increase of acetylcholine release at an end-plate and the loss of postsynaptic acetylcholine receptors, caused by the toxin. The question is whether upregulation of acetylcholine release is a clinically relevant compensatory mechanism in myasthenia gravis or only a feature of the animal model using alpha-bungarotoxin. We investigated electrophysiologically the in vitro acetylcholine release at end-plates of muscles from patients with myasthenia gravis and rats with experimental autoimmune myasthenia gravis where acetylcholine receptor reduction is caused by autoantibody attack. In both human and rat autoimmune myasthenic muscle, the mean quantal content was considerably increased compared with control levels. At each individual myasthenic end-plate, the increase in quantal content appeared to be correlated with the reduction of the amplitude of the miniature end-plate potential. This finding suggests the existence of an important compensatory mechanism in myasthenia gravis, in which retrograde acting factors (i.e., from muscle fiber to nerve terminal) upregulate acetylcholine release.
在重症肌无力中，运动终板处的乙酰胆碱受体因抗受体自身抗体而减少。在通过长期用α-银环蛇毒素处理诱导出类似重症肌无力症状的大鼠的终板处，乙酰胆碱释放增加。在这类大鼠的肌肉中，终板处乙酰胆碱释放的增加与由毒素导致的突触后乙酰胆碱受体的减少之间存在很强的相关性。问题在于乙酰胆碱释放的上调是重症肌无力中一种具有临床相关性的代偿机制，还是仅仅是使用α-银环蛇毒素的动物模型的一个特征。我们用电生理学方法研究了重症肌无力患者以及实验性自身免疫性重症肌无力大鼠（其乙酰胆碱受体减少是由自身抗体攻击所致）肌肉终板处的体外乙酰胆碱释放。在人类和大鼠自身免疫性重症肌无力肌肉中，平均量子含量与对照水平相比显著增加。在每个单独的重症肌无力终板处，量子含量的增加似乎与微小终板电位幅度的降低相关。这一发现表明重症肌无力中存在一种重要的代偿机制，其中逆向作用因子（即从肌纤维到神经末梢）上调乙酰胆碱释放。
