Heterogeneity of calcium channel autoantibodies detected using a small-cell lung cancer line derived from a Lambert-Eaton myasthenic syndrome patient.
We investigated the heterogeneity of anti-voltage-gated calcium channel (VGCC) antibodies in the Lambert-Eaton myasthenic syndrome (LEMS) using a small-cell lung carcinoma line (MB) derived from an LEMS patient. Four of 13 LEMS patients had raised titers of anti-125I-omega-conotoxin-labeled (N-type) VGCCs, measured by radioimmunoassay using line MB as the source of antigen. Antagonists for L-type (nitrendipine and nifedipine) and N-type (omega-conotoxin) VGCCs inhibited K(+)-stimulated (voltage-dependent) Ca2+ flux into this line--by 22% for L-type and 2% for N-type at maximum concentration. Inhibition by the LEMS IgGs, by contrast, ranged from 46 to 78% at a concentration of 2 mg/ml. These differing effects on Ca2+ flux inhibition by LEMS IgGs on the one hand and by L- and N-type channel antagonists on the other, taken together with the observation that many of the sera failed to react with omega-conotoxin-labeled (N-type) channels in the immunoprecipitation assay, suggest that in many LEMS patients the autoantibodies target other VGCC subtypes besides L- or N-types, and that these are important in inducing the myasthenic disorder.
Johnston
I
I
Institute of Molecular Medicine, University of Oxford, John Radcliff Hospital, UK.
Lang
B
B
Leys
K
K
Newsom-Davis
J
J
D001323:Autoantibodies / Q000097:blood* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology; D007700:Kinetics; D015624:Lambert-Eaton Myasthenic Syndrome / Q000097:blood / Q000276:immunology*; D008175:Lung Neoplasms / Q000378:metabolism*; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020960:omega-Conotoxins
D001323:Autoantibodies; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007074:Immunoglobulin G; D010455:Peptides; D020960:omega-Conotoxins; C053423:Conus magus toxin; D011188:Potassium; D002118:Calcium