The effect of myasthenic syndrome antibody on presynaptic calcium channels in the mouse.
1. The action of immunoglobulin G obtained from patients with Lambert-Eaton myasthenic syndrome (LEMS IgG) was investigated by injecting mice, followed by intracellular recordings from the mouse diaphragm. 2. End-plate potential quantal content was studied over a range of Ca2+ concentrations. Curves of log quantal content versus log Ca2+ concentration were shifted to the right by LEMS IgG. For low Ca2+ concentrations, release continued to follow Poisson statistics after LEMS IgG treatment. 3. Miniature end-plate potential (m.e.p.p.) frequency was measured in solutions containing high K+ concentrations. LEMS IgG significantly reduced m.e.p.p. frequency at each K+ concentration studied. 4. M.e.p.p. frequency was measured at fixed high-K+ concentration (15.9 mM) for a range of Ca2+ concentrations. The log-log plot of m.e.p.p. frequency versus Ca2+ concentration was shifted downwards throughout by LEMS IgG. 5. M.e.p.p. frequency was not affected by LEMS IgG in Ca2+-free solutions (K+ concentration 15.9 mM) or in solutions of low Ca2+ concentration (K+ concentration 5.9 mM). 6. At each Ca2+ concentration studied, m.e.p.p. amplitudes were not affected by LEMS IgG. 7. The data suggest that LEMS IgG acts on presynaptic voltage-dependent Ca2+ channels to cause their loss of function, probably by down-regulation.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002118:Calcium / Q000493:pharmacokinetics / Q000502:physiology*; D003964:Diaphragm / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007473:Ion Channels / Q000276:immunology*; D051379:Mice; D009045:Motor Endplate / Q000502:physiology; D009157:Myasthenia Gravis / Q000276:immunology*; D011188:Potassium / Q000494:pharmacology; D013577:Syndrome
D001323:Autoantibodies; D007074:Immunoglobulin G; D007473:Ion Channels; D011188:Potassium; D002118:Calcium