Lambert_1976_Ann.N.Y.Acad.Sci_274_300

Rats inoculated once with nicotinic acetylcholine receptor and adjuvants had two episodes of weakness, the first being acute and transient, starting on day 8, and remitting in a few days, the second, chronic, progressive, and appearing after day 20. In the acute phase, the compound action potential and twitch evoked in weak forelimb muscles by maximal nerve stimulus were greatly reduced. Nerve action potentials were normal, however, and the muscle responded to direct electrical stimulation. Using intracellular microelectrodes, miniature end-plate potentials were difficult to find and often were low in amplitude. Many fibers were functionally denervated; no action potential or end-plate potential was evoked by nerve stimulus, although the muscle fiber responded to direct stimulation. In fibers with EEPs the number of acetylcholine quanta released by nerve impulse, the store of quanta readily available for release and the mobilization rate were low. The diaphragm was similarly, but less severely affected. Recovery from the acute phase occurred in a few days with restoration of the response of forelimb muscle to nerve stimulus, even though MEPP amplitude remained low. In the chronic phase, in both forelimb muscle and diaphragm, MEPP were more easily found, but in all rats MEPP amplitude was below normal whether or not there was weakness or a decrement in the EMG. The number of quanta released by nerve stimulus, the store, and the mobilization rate of quanta were normal in all animals. The titer of antibodies ot syngeneic acetylcholine receptor was elevated in all chronic phase animals. The chronic phase is like myasthenia gravis, but rats with MEPP amplitudes as low as those in patients with MG frequently were not weak, because the number of ACh quanta released per nerve impulse is greater in the rat than in man.