Synaptotagmin can cause an immune-mediated model of Lambert-Eaton myasthenic syndrome in rats.
The possible antigenicity of synaptotagmin, a synaptic vesicle protein acting as a cooperative calcium (Ca2+) 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 Ca2+ 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 Ca2+ 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 Ca2+ channel complex may be involved in the pathogenesis of Lambert-Eaton myasthenic syndrome. The peptide (residues 1-30)-immunized rats showed no electrophysiological abnormality.
Takamori
M
M
Department of Neurology, Kanazawa University School of Medicine, Japan.
Hamada
T
T
Komai
K
K
Takahashi
M
M
Yoshida
A
A
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D016466:CHO Cells; D002135:Calcium-Binding Proteins; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D015624:Lambert-Eaton Myasthenic Syndrome / Q000139:chemically induced* / Q000276:immunology* / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D008839:Microelectrodes; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009469:Neuromuscular Junction / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D009435:Synaptic Transmission / Q000502:physiology; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050857:Synaptotagmins