Antibodies to acetylcholine receptors in rabbits: immunochemical and electrophysiological studies

Acetylcholine receptors (AChR), purified from electric eel and Torpedo by affinity chromatography using a synthetic quaternary ammonium ligand, bound 10 nmole alpha-bungarotoxin (alpha-BuTx) per mg of protein and demonstrated a common subunit. Rabbits, immunized with either eel or Torpedo/AChR, developed flaccid paralysis barely altered by anticholinesterases and died 48 hours after the first sign of paralysis. In paralyzed animals, repetitive stimulation at low rates induced a 50% to 90% decrement of evoked potentials, temporarily reversed by edrophonium. Extracellular and introcellular MEPP amplitudes were 40% to 50% of controls. Serum and isolated IgG formed single immunoprecipitin lines against the antigens. AChR-antibody complexes did not bind alpha-BuTx, whereas alpha-BuTx-AChR complexes bound antibody if the antibody was specific for that AChR. Torpedo and eel AChR showed partial idenity with both antisera. Rat diaphragms and eel electroplax incubated with antisera to Torpedo and eel AChR showed a 50%-60% reduction in carbamylcholine depolarization. These studies demonstrate differences between eel and Torpedo AChR induce a block in neuromuscular transmission in rabbits with features of myasthenia gravis.