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Synaptotagmin can cause an immune‐mediated model of Lambert‐Eaton myasthenic syndrome in rats
Author(s) -
Takamori Masaharu,
Hamada Toshio,
Komai Kiyonobu,
Takahashi Masami,
Yoshida Akira
Publication year - 1994
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410350112
Subject(s) - synaptotagmin 1 , lambert eaton myasthenic syndrome , neuromuscular junction , exocytosis , electrophysiology , myasthenia gravis , chemistry , endocrinology , extracellular , acetylcholine receptor , synaptic vesicle , antibody , medicine , biology , neuroscience , immunology , receptor , vesicle , biochemistry , secretion , membrane
The possible antigenicity of synaptotagmin, a synaptic vesicle protein acting as a cooperative calcium (Ca 2+ ) receptor in exocytosis, was tested to determine whether it is involved in the induction of Lambert‐Eaton myasthenic syndrome in which antibodies against voltage‐dependent Ca 2+ channels or related molecules play a pathogenic role. Repeated injections to Lewis rats with peptides of synaptotagmin residues 20 through 53 or 1 through 30 that are presumably exposed at the nerve terminal surface during exocytosis induced corresponding antipeptide antibodies; on immunoblots, antibodies recognized synaptotagmin that was expressed in the clonal cells. Electrophysiologically, the peptide (residues 20–53)‐immunized rats showed (1) reduced acetylcholine quantal content of end‐plate potential, (2) an increase in quantal content at high extracellular Ca 2+ concentration, and (3) early facilitation followed by less marked depression of end‐plate potential amplitude at a tetanic rate of repetitive nerve stimulation. Findings are similar to those in human Lambert‐Eaton myasthenic syndrome and passively transferred Lambert‐Eaton myasthenic syndrome in mice, and thus suggest that antibody to a synaptotagmin–voltage‐dependent Ca 2+ channel complex may be involved in the pathogenesis of Lambert‐Eaton myasthenic syndrome. The peptide (residues 1–30)‐immunized rats showed no electrophysiological abnormality.