Presynaptic membrane active zones are related to synaptic vesicle exocytosis, and the large intramembrane particles in these zones may represent voltage‐sensitive calcium channels. We tested the hypothesis that an abnormality of the zones is associated with the low probability of quantal release in the Lambert‐Eaton myasthenic syndrome (LEMS). Freeze‐fractured presynaptic membranes were studied in nine patients with LEMS (227 end‐plates) and in 14 controls (148 end‐plates). Satisfactory replicas of 94 LEMS and 83 control presynaptic membrane P‐faces were obtained. Presynaptic membrane areas were estimated by stereometric analysis. The LEMS samples showed a marked decrease in active zones and active zone particles per unit area. The average number of particles per active zone was also reduced. Clusters of large particles were observed with increased frequency in the LEMS samples. These may have arisen by aggregation of active zone particles. There was no decrease in the overall density of intramembrane particles not associated with active zones or clusters. The distribution of these particles according to size resembled the control distribution except for a small decrease in the frequency of 5.3–5.8 nm particles. The findings can explain the reduced quantal release in LEMS, and strongly suggest that active zone particles are targets of the pathogenic autoantibodies recently demonstrated in this disease.
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Physiology (medical)