Passive transfer of Lambert-Eaton myasthenic syndrome in mice: decreased rates of resting and evoked release of acetylcholine from skeletal muscle.

Mice were injected for 1-2 months daily with 10 mg immunoglobulin G (IgG) from four patients with Lambert-Eaton myasthenic syndrome (LEMS); control mice were injected with pooled human IgG from normal donors. Gastrocnemius muscles were homogenised for the assay of acetylcholine (ACh), choline acetyltransferase (ChAT), and cholinesterase (ChE). The ACh, ChAT, and ChE contents of gastrocnemius muscles from "LEMS mice" were about the same as the control values, which were 180 pmol, 40 nmol X h-1 (37 degrees C), and 15 mumol X h-1 (37 degrees C), respectively. Hemidiaphragms were treated with an irreversible ChE inhibitor (Soman) and incubated at 20 degrees C for estimation of ACh release. Resting ACh release from experimental muscles was reduced by about 25% (P2 less than 0.05) and the release evoked by 3 s-1 nervous stimulation by 50% (P2 less than 0.05). On the other hand, 50 mM KCl-induced transmitter release was not abnormal in LEMS mice. The findings indicate that IgG antibody from patients with LEMS may bind to nerve terminal determinants that are involved in quantal and nonquantal ACh release.