ANTIGENS ASSOCIATED WITH N-TYPE AND L-TYPE CALCIUM CHANNELS IN LAMBERT-EATON MYASTHENIC SYNDROME

In Lambert-Eaton myasthenic syndrome neurotransmitter release is reduc ed by an autoimmune response directed against the calcium channel comp lex of the nerve terminal. Autoantibodies were detected by immunopreci pitation assays using solubilized receptors labeled with ligands selec tive for N-type (I-125-omega conotoxin GVIA) and L-type ([H-3]PN200-11 0) calcium channels. Sera with a high antibody titer (>3 nM) against r at brain N-type channels contained autoantibodies that immunoprecipita ted neuronal and muscle L-type channels. These IgG fractions stained a 55-kDa protein in immunoblots of purified skeletal muscle dihydropyri dine receptor, suggesting that they contain autoantibodies against the beta subunit of the calcium channel. A distinct antibody population i n the same fractions reacted with a nerve terminal 65-kDa protein that is unrelated to the beta subunit and displays properties similar to t hose of synaptotagmin.