Ultrastructural aspects of acetylcholine receptor turnover at the normal end-plate and in autoimmune myasthenia gravis

Acetylcholine receptor (AChR) deficiency at the myasthenic end-plate has been attributed to complement-mediated lysis of the junctional folds and to increased fractional degradation rate of AChR cross-linked by myasthenic immunoglobulin. This paper addresses the manner in which AChR is internalized and degraded at the normal end-plate and provides morphologic evidence for accelerated AChR degradation at the end-plate of rats with experimental autoimmune myasthenia gravis (EAMG). We sequentially traced the fate of end-plate AChR labeled in vivo with intramuscularly-injected peroxidase-alpha-bungarotoxin (PBGT) in control rats and rats with chronic EAMG. At both control and EAMG end-plates, AChR is internalized by endocytosis. The endocytosed vesicles containing AChR are transferred into the lysosomal compartment which extends from the junctional folds into the junctional sarcoplasm. Regardless of whether the initial intensity of the reaction for AChR at the EAMG end-plate appeared normal or reduced. AChR d isappeared more rapidly from the EAMG than from the control end-plates. Despite the accelerated fractional turnover rate of end-plate AChR in EAMG, the postsynaptic membrane surface which could be labeled with PBGT for AChR remained unchanged over a 120-hour period. These data suggest that end-plate AChR is at a steady state in chronic EAMG.