The
Lambert-Eaton myasthenic syndrome (LES) is an autoimmune presynaptic disorder of peripheral
cholinergic neurotransmission in which there is often an associated
small cell lung carcinoma (SCC). SCC lines established from patients with and without LES exhibit a Ca2+ influx response to depolarization by K+ that is consistent with the presence of voltage-gated Ca2+ channels.
Autoantibodies antagonistic to SCC Ca2+ channel activity were found exclusively in patients with LES, independent of
cancer status. Depolarization-induced uptake of 45Ca2+ by SCC lines was reduced maximally after 3-4 days of exposure to serum
immunoglobulins from 14 of 19 LES patients, while 53 control
immunoglobulins (including patients with SCC, other
tumors, other
paraneoplastic syndromes, and other neurological and
autoimmune diseases) were without effect. The snail
neurotoxin omega-conotoxin of subtype GVIA, which is a specific antagonist of presynaptic Ca2+ channels, inhibited K+-stimulated Ca2+ uptake in a dose-dependent manner that was essentially irreversible.
Adenosine, reported to be a specific antagonist of neuronal Ca2+ channels, also impaired voltage-stimulated Ca2+ influx in SCC. Use of LES patients'
IgG and
omega-conotoxin in further studies of SCC may facilitate identification and purification of the LES
antigen(s) and yield a quantitative serological test for diagnosing this autoimmune
paraneoplastic syndrome.