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 channe l (VGCC) antibodies in the Lambert-Eaton myasthenic syndrome (LEMS) us ing a small-cell lung carcinoma line (MB) derived from an LEMS patient . Four of 13 LEMS patients had raised titers of anti-I-125-omega-conot oxin-labeled (N-type) VGCCs, measured by radioimmunoassay using line M B 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 d iffering 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 VGC C subtypes besides L- or N-types, and that these are important in indu cing the myasthenic disorder.