Effects of botulinum neurotoxin and Lambert-Eaton myasthenic syndrome IgG at mouse nerve terminals

Abstract

The interaction between two presynaptically acting agents, Lambert-Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) and purified botulinum neurotoxin (BoNT) type A, was studied. Intracellular microelectrode recordings were carried out on mouse muscles after injection with LEMS IgG. BoNT was either injected before recordings were made or applied in vitro. The time course of the in vitro actions of BoNT on miniature end-plate potential and end-plate potential parameters were not affected by pretreatment with LEMS IgG. After in vivo injection of BoNT, end-plate potential quantal content was reduced to less than 2% of control values, whether or not LEMS IgG had also been previously given. Quantitative electron-microscope autoradiographical analysis showed that neither the binding of 125I-BoNT to acceptors on the nerve terminal membrane nor the pattern of its internalisation were affected by pretreatment with LEMS IgG. We conclude that the effects of BoNT are not affected by LEMS IgG, suggesting different presynaptic binding sites for the two agents.