Walsh & Hoyt: Normal Neuromuscular Transmission

To understand the pathophysiology of the defects in myasthenia gravis (MG) and other disorders that damage the neuromuscular junction (NMJ), it is necessary to have some knowledge of the basic events of neuromuscular transmission. Acetylcholine (ACh), the natural transmitter, is synthesized chiefly in the motor nerve terminals and is stored in vesicles for subsequent release. Neurotransmission begins with the release of the contents of the vesicles by a process of exocytosis that occurs at specialized release sites. The probability of vesicular binding and release at these sites depends directly on calcium concentrations in nerve terminals. A change in this probability of release is the main pathophysiologic feature in the Lambert-Eaton myasthenic syndrome and botulism. The vesicle release sites are located directly opposite the areas of highest concentration of ACh receptors on the postsynaptic membranes, thus minimizing the distance that the transmitter must travel to reach the receptor site. When ACh combines with its receptor, a transient increase of permeability to sodium and potassium ions occurs, resulting in membrane depolarization.