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  1. Marguerite Hill
  1. Correspondence to:
 Dr Marguerite Hill, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol BS16 1LE, UK; 

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Neuromuscular junction (NMJ) disorders result from destruction, malfunction or absence of one or more key proteins involved in neuromuscular transmission, illustrated diagrammatically in fig 1. The most common pathology is antibody mediated damage or down regulation of ion channels or receptors, resulting in myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and acquired neuromyotonia (Isaac’s syndrome). Not surprisingly these three conditions share many common features (table 1). A second important group of disorders are the congenital myasthenic syndromes caused by mutations in NMJ proteins. Detailed discussion of these rare conditions is beyond the scope of this short review but interested readers are referred to a recent review by Engel and Ohno.1

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Table 1

Comparison of the key features of the different autoimmune conditions that affect the neuromuscular junction

Figure 1

Diagrammatic representation of neuromuscular transmission. (1) Action potential arriving at nerve terminal triggers opening of voltage gated calcium channels (VGCCs) and entry of calcium. (2) Rise in intracellular calcium triggers release of packets of acetylcholine (ACh). (3) Interaction of ACh with ACh receptors (AChR) depolarises post-synaptic membrane. (4) Voltage gated sodium channels (VGSCs) open, triggering muscle action potential. (5) ACh esterase (AChE) breaks ACh into acetyl and choline, which are taken up by the nerve terminal to be reformed into ACh. (6) Opening of voltage gated potassium channels (VGKCs) repolarises nerve terminal.



In anti-AChR antibody positive MG, autoantibodies target the acetylcholine (ACh) receptor (AChR) resulting in receptor blockade, down regulation, and complement mediated destruction, thus reducing the number of receptors available to interact with the ACh released from the presynaptic nerve terminal. Complement activation attracts activated macrophages, which cause significant damage to the synaptic folds and loss of voltage gated sodium channels, which in turn increases the threshold required to initiate a muscle action potential. The consequence of the combined loss of AChRs and …

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