The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease in which 
autoantibodies are directed against voltage-gated calcium channels (VGCCs) at 
presynaptic nerve terminals. We first demonstrated the presence of P/Q-type and 
N-type VGCCs in digitonin extracts prepared from human and rabbit cerebellum 
using the specific ligands 125I-omega-conotoxin MVIIC (125I-omega-CmTx) and 
125I-omega-conotoxin GVIA (125I-omega-CgTx), respectively. We then tested sera 
from 72 LEMS patients' 25 with proven small cell lung cancer (SCLC) and 66 
healthy or other neurological, SCLC or autoimmune disease controls in an 
immunoprecipitation assay using 125I-omega-CmTx-labelled (P/Q-type) VGCCs in 
human cerebellar extract. Sixty-six of 72 LEMS serum samples (91.7%) were 
positive for the presence of VGCC antibodies, as defined as a titre greater than 
3 standard deviations above the mean for the healthy controls (n = 22). Rabbit 
cerebellar extract as antigen gave similar results (r = 0.94, P < 0.001, n = 
30). By contrast, only 24/72 (33%) LEMS sera were positive in the assay for 
anti-N-type VGCC antibodies using 125I-omega-CgTx. All these 24 were also 
positive in the 125I-omega-CmTx assay. All healthy and disease control sera were 
negative in both assays. The anti-P/Q-type VGCC antibody titres did not 
correlate with an electrophysiological index of disease severity across 
individuals; however, longitudinal studies in a LEMS patient with SCLC receiving 
chemotherapy, and in a non-SCLC LEMS patient receiving immunosuppressive therapy 
showed an inverse relation between antibody titre and disease severity. These 
results support the view that anti-P/Q-type VGCC antibodies are implicated in 
the motor disorder in LEMS, and show that the omega-CmTx radioimmunoassay is a 
highly specific and sensitive means of detecting them.