Rash_1981_Lab.Invest_44_519

Freeze fracture replicas of neuromuscular junctions from normal human patients and those with facioscapulohumeral and limb girdle muscular dystrophies, progressive muscular atrophy, and myasthenia gravis were examined by stereoscopic electron microscopy. Endplates from most human patients closely resemble those of normal adult rats fixed by intravascular perfusion. However, endplates from patients with myasthenia gravis have clinically relevant alterations in postsynaptic membrane infrastructure, including decreased number of P-face particles and increased number of E-face particles in the crests of the junctional folds. Other junctional fold crests are narrowed or obliterated and are replaced by incompletely sealed membrane vesicles rich in intramembrane particles. Similar alterations are not produced in rat endplates by immersion fixation, exposure to low pH, brief hypoxia, prolonged or extreme hypothermia, prolonged or high frequency nerve stimulation, or by prolonged nerve quiescence. Rather, the destructive alterations observed in junctional fold membranes in myasthenia gravis endplates are correlated with decreased acetylcholine sensitivity and to removal of endplate acetylcholine receptors by immunologic processes.