Cetin Hakan, Beeson David, Vincent Angela, Webster Richard
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
Front Mol Neurosci. 2020 Sep 8;13:581097. doi: 10.3389/fnmol.2020.581097. eCollection 2020.
The neuromuscular junction (NMJ) is a highly developed synapse linking motor neuron activity with muscle contraction. A complex of molecular cascades together with the specialized NMJ architecture ensures that each action potential arriving at the motor nerve terminal is translated into an action potential in the muscle fiber. The muscle-type nicotinic acetylcholine receptor (AChR) is a key molecular component located at the postsynaptic muscle membrane responsible for the generation of the endplate potential (EPP), which usually exceeds the threshold potential necessary to activate voltage-gated sodium channels and triggers a muscle action potential. Two AChR isoforms are found in mammalian muscle. The fetal isoform is present in prenatal stages and is involved in the development of the neuromuscular system whereas the adult isoform prevails thereafter, except after denervation when the fetal form is re-expressed throughout the muscle. This review will summarize the structural and functional differences between the two isoforms and outline congenital and autoimmune myasthenic syndromes that involve the isoform specific AChR subunits.
神经肌肉接头（NMJ）是一种高度发达的突触，它将运动神经元活动与肌肉收缩联系起来。一系列分子级联反应与特殊的神经肌肉接头结构共同确保到达运动神经末梢的每个动作电位都能转化为肌肉纤维中的动作电位。肌肉型烟碱型乙酰胆碱受体（AChR）是位于突触后肌膜的关键分子成分，负责终板电位（EPP）的产生，终板电位通常超过激活电压门控钠通道所需的阈值电位，并触发肌肉动作电位。在哺乳动物肌肉中发现了两种AChR亚型。胎儿亚型在产前阶段存在，参与神经肌肉系统的发育，而成人亚型此后占主导地位，但在去神经支配后除外，此时胎儿型会在整个肌肉中重新表达。本综述将总结两种亚型之间的结构和功能差异，并概述涉及亚型特异性AChR亚基的先天性和自身免疫性重症肌无力综合征。
