IgG from patients with Lambert-Eaton syndrome blocks voltage-dependent calcium channels.
Lambert-Eaton syndrome, an autoimmune disorder frequently associated with small-cell carcinoma of the lung, is characterized by impaired evoked release of acetylcholine from the motor nerve terminal. Immunoglobulin G (IgG) antibodies from patients with the syndrome, applied to bovine adrenal chromaffin cells, reduced the voltage-dependent calcium channel currents by about 40 percent. When calcium was administered directly into the cytoplasm, however, the IgG-treated cells exhibited normal exocytotic secretion, as assayed by membrane capacitance measurement. Measurement with the fluorescent calcium indicator fura-2 indicated that the IgG treatment reduced potassium-stimulated increase in free intracellular calcium concentration. The pathogenic IgG modified neither kinetics of calcium channel activation nor elementary channel activity, suggesting that a reduction in the number of functional calcium channels underlies the IgG-induced effect. Therefore, Lambert-Eaton syndrome IgG reacts with voltage-dependent calcium channels and blocks their function, a phenomenon that can account for the presynaptic impairment characteristic of this disorder.
D000311:Adrenal Glands / Q000503:physiopathology; D001323:Autoantibodies / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000276:immunology; D002462:Cell Membrane / Q000502:physiology; D002838:Chromaffin System / Q000503:physiopathology; D004553:Electric Conductivity; D005089:Exocytosis; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology; D009468:Neuromuscular Diseases / Q000276:immunology* / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism; D013569:Synapses / Q000276:immunology / Q000502:physiology; D013577:Syndrome; D013779:Tetrodotoxin / Q000494:pharmacology
D001323:Autoantibodies; D001572:Benzofurans; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D007473:Ion Channels; D013779:Tetrodotoxin; D012964:Sodium; D002118:Calcium; D016257:Fura-2