Hughes Benjamin W, Kusner Linda L, Kaminski Henry J
Department of Neurology, Case Western University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Muscle Nerve. 2006 Apr;33(4):445-61. doi: 10.1002/mus.20440.
The neuromuscular junction (NMJ) is a complex structure that serves to efficiently communicate the electrical impulse from the motor neuron to the skeletal muscle to signal contraction. Over the last 200 years, technological advances in microscopy allowed visualization of the existence of a gap between the motor neuron and skeletal muscle that necessitated the existence of a messenger, which proved to be acetylcholine. Ultrastructural analysis identified vesicles in the presynaptic nerve terminal, which provided a beautiful structural correlate for the quantal nature of neuromuscular transmission, and the imaging of synaptic folds on the muscle surface demonstrated that specializations of the underlying protein scaffold were required. Molecular analysis in the last 20 years has confirmed the preferential expression of synaptic proteins, which is guided by a precise developmental program and maintained by signals from nerve. Although often overlooked, the Schwann cell that caps the NMJ and the basal lamina is proving to be critical in maintenance of the junction. Genetic and autoimmune disorders are known that compromise neuromuscular transmission and provide further insights into the complexities of NMJ function as well as the subtle differences that exist among NMJ that may underlie the differential susceptibility of muscle groups to neuromuscular transmission diseases. In this review we summarize the synaptic physiology, architecture, and variations in synaptic structure among muscle types. The important roles of specific signaling pathways involved in NMJ development and acetylcholine receptor (AChR) clustering are reviewed. Finally, genetic and autoimmune disorders and their effects on NMJ architecture and neuromuscular transmission are examined.
神经肌肉接头（NMJ）是一种复杂的结构，其作用是有效地将运动神经元的电冲动传递给骨骼肌，以发出收缩信号。在过去的200年里，显微镜技术的进步使人们能够观察到运动神经元和骨骼肌之间存在间隙，这就需要一种信使的存在，后来证明这种信使是乙酰胆碱。超微结构分析确定了突触前神经末梢中的囊泡，这为神经肌肉传递的量子性质提供了一个很好的结构关联，并且对肌肉表面突触褶皱的成像表明，需要底层蛋白质支架的特化。过去20年的分子分析证实了突触蛋白的优先表达，这种表达由精确的发育程序引导，并由来自神经的信号维持。虽然常常被忽视，但覆盖神经肌肉接头的施万细胞和基膜在维持接头方面正被证明至关重要。已知遗传和自身免疫性疾病会损害神经肌肉传递，并为神经肌肉接头功能的复杂性以及神经肌肉接头之间存在的细微差异提供进一步的见解，这些差异可能是肌肉群对神经肌肉传递疾病易感性不同的基础。在这篇综述中，我们总结了突触生理学、结构以及不同肌肉类型之间突触结构的差异。我们还综述了参与神经肌肉接头发育和乙酰胆碱受体（AChR）聚集的特定信号通路的重要作用。最后，我们研究了遗传和自身免疫性疾病及其对神经肌肉接头结构和神经肌肉传递的影响。
