Basic concepts and classification

The neuromuscular junction (NMJ) is undoubtedly the most intensively studied, best understood, and arguably the simplest of mammalian synapses. Its role is to amplify the relatively weak electrical impulses that travel down the motor nerve sufficiently to trigger electrical impulses in the much larger muscle cell, and thereby lead to muscle contraction. It accomplishes this by translating the neural electrical impulse to a chemical signal, acetylcholine (ACh), which in turn elicits an amplified electrical depolarization at the level of the muscle. A single event of neuromuscular transmission takes place in less than a millisecond. Although this process is normally powerful, swift and efficient, it is highly vulnerable to a wide variety of insults, including genetic errors, autoimmune diseases, biological poisons made by bacteria, plants and animals, and pharmacological drugs or chemical warfare agents manufactured by humans. Any alteration in the highly complex and coordinated processes of ACh synthesis, storage and release; transmission across the junction; structure or function of the acetylcholine receptors (AChRs); termination of the event by the enzyme acetylcholinesterase (AChE); or impairment of neighbouring ion channels, can lead to muscular weakness. In this sense, the junction is the Achilles heel of the neuromuscular system. In order to understand the many disorders that can affect the NMJ, it is important to review the basic anatomy and physiology of neuromuscular transmission.

Although one motor nerve cell may innervate as few as 3 or as many as 1500 muscle fibres, each mature muscle fibre is innervated by only a single axonal branch, and has only a single NMJ. The junction is comprised of contributions from both the motor nerve and the muscle cell, including: a motor nerve fibre which branches to form specialized nerve terminals; the basal lamina which intervenes between nerve terminals and muscle cells; the highly invaginated postsynaptic membrane, with concentrations of AChRs at the peaks of the primary folds; AChE in secondary folds; and Schwann cells that roof over the NMJ (Fig. 69.1). In simplest outline, the process of neuromuscular transmission begins with an action potential that depolarizes the motor nerve terminal, triggering the entry of calcium, which leads to the release of ACh from storage vesicles in the nerve terminals.