Vincent A, Beeson D, Lang B
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Eur J Biochem. 2000 Dec;267(23):6717-28. doi: 10.1046/j.1432-1033.2000.01785.x.
The neuromuscular junction is the target of a variety of autoimmune, neurotoxic and genetic disorders, most of which result in muscle weakness. Most of the diseases, and many neurotoxins, target the ion channels that are essential for neuromuscular transmission. Myasthenia gravis is an acquired autoimmune disease caused in the majority of patients by antibodies to the acetylcholine receptor, a ligand-gated ion channel. The antibodies lead to loss of acetylcholine receptor, reduced efficiency of neuromuscular transmission and muscle weakness and fatigue. Placental transfer of these antibodies in women with myasthenia can cause fetal or neonatal weakness and occasionally severe deformities. Lambert Eaton myasthenic syndrome and acquired neuromyotonia are caused by antibodies to voltage-gated calcium or potassium channels, respectively. In the rare acquired neuromyotonia, reduced repolarization of the nerve terminal leads to spontaneous and repetitive muscle activity. In each of these disorders, the antibodies are detected by immunoprecipitation of the relevant ion channel labelled with radioactive neurotoxins. Genetic disorders of neuromuscular transmission are due mainly to mutations in the genes for the acetylcholine receptor. These conditions show recessive or dominant inheritance and result in either loss of receptors or altered kinetics of acetylcholine receptor channel properties. Study of these conditions has greatly increased our understanding of synaptic function and of disease aetiology.
神经肌肉接头是多种自身免疫性、神经毒性和遗传性疾病的靶点，其中大多数疾病会导致肌肉无力。大多数此类疾病以及许多神经毒素，都靶向神经肌肉传递所必需的离子通道。重症肌无力是一种获得性自身免疫性疾病，大多数患者是由针对乙酰胆碱受体（一种配体门控离子通道）的抗体引起的。这些抗体导致乙酰胆碱受体丧失、神经肌肉传递效率降低以及肌肉无力和疲劳。重症肌无力女性患者体内的这些抗体会通过胎盘转移，导致胎儿或新生儿肌无力，偶尔还会造成严重畸形。兰伯特 - 伊顿肌无力综合征和获得性神经性肌强直分别由针对电压门控钙通道或钾通道的抗体引起。在罕见的获得性神经性肌强直中，神经末梢复极化减弱会导致肌肉自发且重复的活动。在这些疾病中，通过用放射性神经毒素标记的相关离子通道进行免疫沉淀来检测抗体。神经肌肉传递的遗传性疾病主要是由于乙酰胆碱受体基因的突变。这些病症表现为隐性或显性遗传，会导致受体丧失或乙酰胆碱受体通道特性的动力学改变。对这些病症的研究极大地增进了我们对突触功能和疾病病因的理解。
