title: Calcium channel peptide can cause an autoimmune-mediated model of Lambert-Eaton myasthenic syndrome in rats.
abstract: The Lambert-Eaton myasthenic syndrome (LEMS) is a disorder of neuromuscular transmission characterized by the reduced quantal release of acetylcholine from the motor nerve terminal, wherein the P/Q-type of voltage-gated calcium channel (VGCC) and is attacked by a majority of LEMS antibodies. Using the molecular structure of the alpha1 subunit (consisting of 4 domains) of the P/Q-type VGCC as a reference, we synthesized the extracellular region (S5-S6 linker) of the domain III, known as the segment which plays an important role in channel functions. Six of the ten Lewis rats immunized with this synthetic peptide conjugated with carrier protein showed moderate weakness (grade 1 in a 3-graded scale, for myasthenic weakness in experimental animals) and a reduction in acetylcholine quantum content of end-plate potentials. Antipeptide antibodies raised in test rats reacted with omega-conotoxin MVIIC-sensitive cerebellar extract (P/Q-type VGCC) and the domain III peptide inhibited the binding of rat antibodies to VGCCs. Our findings suggest the identification of one of the potential epitopes of LEMS antibodies.
authors.affiliation: Department of Neurology, Kanazawa University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Komai
authors.forename: K
authors.initials: K
authors.lastname: Iwasa
authors.forename: M
authors.initials: M
authors.lastname: Takamori
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology; D015220:Calcium Channels / Q000097:blood / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015624:Lambert-Eaton Myasthenic Syndrome / Q000097:blood / Q000276:immunology*; D010455:Peptides / Q000097:blood / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000906:Antibodies; D015220:Calcium Channels; D010455:Peptides