Serum and plasma from patients with Lambert-Eaton Myasthenic Syndrome reduce depolarization-dependent uptake of 45Ca2+ into rat cortical synaptosomes.
The reduction in nerve-evoked release of transmitter at the neuromuscular junction of patients with Lambert-Eaton Myasthenic Syndrome (LEMS) is thought to be caused by a circulating autoantibody to calcium channels of presynaptic motor nerve terminals. Studies were undertaken to determine whether acute application of plasma and serum from patients with LEMS or small cell carcinoma (SCC) would reduce depolarization-dependent uptake of 45Ca2+ into isolated nerve terminals of the central nervous system (CNS). Net potassium-stimulated influx was reduced by sera and plasma from patients with LEMS but not by sera from patients with SCC. Lactate dehydrogenase (LDH) release from synaptosomes incubated with plasma or serum from patients with LEMS was not increased over control. These results are significant because: (1) they demonstrate that acute exposure to a circulating factor in sera/plasma from a patient with LEMS is sufficient to inhibit Ca2+ channel activity in isolated nerve terminals, as opposed to chronic regimens used in other models for the disease; (2) they indicate that the existence of SCC alone is insufficient to trigger a LEMS-like autoimmune response; (3) they suggest that Ca2+ channels of nerve terminals secreting different transmitters may share common epitopes recognized by the LEMS autoantibody; and (4) they suggest that synaptosomes will be useful in determining the neurochemical site and specificity of the LEMS autoantibody.
Hewett
S J
SJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Atchison
W D
WD
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002540:Cerebral Cortex / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015624:Lambert-Eaton Myasthenic Syndrome / Q000097:blood*; D008297:Male; D010949:Plasma / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*
D002132:Calcium Radioisotopes; D007770:L-Lactate Dehydrogenase; D002118:Calcium