I. Johnston et al., HETEROGENEITY OF CALCIUM-CHANNEL AUTOANTIBODIES DETECTED USING A SMALL-CELL LUNG-CANCER LINE DERIVED FROM A LAMBERT-EATON MYASTHENIC SYNDROME PATIENT, Neurology, 44(2), 1994, pp. 334-338
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.