Diverse aspects of vulnerability at the neuromuscular junction

Neuromuscular junctions provide the essential link between the nervous system and muscles. In healthy humans, neuromuscular junctions reliably convert every impulse in a motor neuron into a corresponding action potential in each muscle fibre innervated by that particular motor neuron. However, the structural and molecular complexity of neuromuscular junctions means that they contain many potential targets for deleterious mutations. In addition, their location at the relatively unprotected periphery of the nervous system heightens the vulnerability of neuromuscular junctions to injury from a variety of chemical and mechanical agents. Detailed investigations of patients with impaired neuromuscular transmission have provided important insights into how a variety of pathological processes may conspire to impair neuromuscular transmission.The reliability of neuromuscular transmission depends both on how much acetylcholine is released from the nerve terminal and how it acts to excite the muscle fibre membrane (Slater, 2008). Two papers in this issue of Brain add to the list of myasthenic conditions in which the action of acetylcholine is impaired (Klooster et al. , 2012; Webster et al. , 2012). Taken together, these results emphasize that effectiveness of the transmitter depends on both the detailed molecular properties of the ion channels at the core of the acetylcholine receptors (AChRs) and how many of those receptors are within the range of transmitter molecules released from the nerve terminal.In recent years, many mutations have been found in genes encoding key proteins at neuromuscular junctions that account for inherited defects of …