Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line.
Certain cancers exert unexplained remote effects on the nervous system. Small cell carcinoma (SCC) of the lung, a tumour capable of spike electrogenesis and which is of possible neural crest origin, is present in approximately 70% of patients with the Lambert-Eaton myasthenic syndrome (LEMS), a disorder characterized by fatigable muscle weakness. Patients with this syndrome have a defect in the (Ca2+-dependent) quantal release of acetylcholine from motor nerve terminals evoked by a nerve impulse or by high K+ (ref.5), and a decreased number of presynaptic active zone particles. The physiological and morphological features of the syndrome can be transferred to mice by the patients' IgG, consistent with an autoantibody interfering with the function of voltage-dependent Ca2+ channels. Here we demonstrate that K+-induced 45Ca2+ flux in a cultured human SCC line is significantly reduced by LEMS IgG, suggesting that in SCC-LEMS an autoantibody to tumour Ca2+-channel determinants is triggered; its cross-reaction with similar determinants at the motor nerve terminal could lead to the remote neurological syndrome.
A
A
Roberts
S
S
Perera
B
B
Lang
A
A
Vincent
J
J
Newsom-Davis
D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000503:physiopathology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007473:Ion Channels / Q000276:immunology*; D008564:Membrane Potentials; D009135:Muscular Diseases / Q000276:immunology*; D011188:Potassium / Q000494:pharmacology; D013577:Syndrome
D007074:Immunoglobulin G; D007473:Ion Channels; D011188:Potassium; D002118:Calcium