Experimental autoimmune myasthenia gravis: the rabbit as an animal model.

Rabbits immunized with acetylcholine (ACh) receptor purified from Torpedo electroplax were studied after they were paralyzed and exhibiting respiratory distress. Intercostal muscles from the immunized rabbits had reduced amplitude of miniature end-plate potentials (MEPPs) as well as reduced junctional ACh sensitivity. However, a large percentage of the cells studied (40%), which exhibited no MEPPs, had junctional ACh sensitivity that was 45% of normal. It is suggested that, unlike myasthenic patients, such paralyzed and dying rabbits may have, in addition to postsynaptic damage, neurons that are damaged or separated from the muscle. Serums from six paralyzed rabbits inhibited binding of [3H]ACh and [125I]alpha-bungarotoxin to Torpedo ACh-receptor to varying degrees: 18.8--95.5% and 42.5--86.1%, respectively. Immune serums also inhibited the carbamylcholine-induced 22Na efflux from Torpedo microsacs, but neither they nor the immunoglobulins inhibited neuromuscular transmission when applied to intercostal muscles from a control rabbit. The data suggest that homology between receptor and antibody is important for inhibition of ACh binding to its receptor and its function. The role of complement in pathogenesis is also discussed, and so is the relationship of the ACh-receptor to its ionic channel.