TY - JOUR
T1 - Passive transfer of Lambert-Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic membrane active zones
AU - Fukunaga, H.
AU - Engel, A. G.
AU - Lang, B.
AU - Newsom-Davis, J.
AU - Vincent, A.
PY - 1983
Y1 - 1983
N2 - In the Lambert-aston myasthenic syndrome (LEMS), there is a decreased release of acetylcholine quanta from the nerve terminal by nerve impulse. Recently, an autoimmune origin of LEMS was documented by passive transfer of its electrophysiologic features from man to mouse with IgG. Freeze-fracture electron microscopy of LEMS neuromuscular junctions has revealed a paucity of presynaptic membrane active zones. Thus, the active zones might be the targets of the pathogenic autoantibodies in LEMS. To test this assumption, freeze-fracture electron microscopic studies were done in mice injected with 10 mg of IgG daily from each of three LEMS patients and in control mice treated with normal IgG or no IgG. IgG from patients 1 and 2 impaired neuromuscular transmission in mice, but IgG from patient 3 failed to do so. After 52-69 days of treatment, diaphragm or anterior tibial muscles were removed and coded. Paired muscles from control mice and mice receiving LEMS IgG were studied 'blindly'. Satisfactory freeze-fracture replicas of 185 presynaptic membrane P-faces were analyzed by stereometric methods. In mice treated with LEMS IgG that was pathogenic by electrophysiologic criteria, there was a selective depletion of active zones and active-zone particles but not of other membrane particles and there was a concomitant increase of large membrane particles aggregated into clusters. These findings provide additional evidence that the active zones facilitate quantal transmitter release by nerve impulse, lend further support to the assumption that the active-zone particles are Ca2+ channels, and establish mediation of the membrane lesions in LEMS by IgG.
AB - In the Lambert-aston myasthenic syndrome (LEMS), there is a decreased release of acetylcholine quanta from the nerve terminal by nerve impulse. Recently, an autoimmune origin of LEMS was documented by passive transfer of its electrophysiologic features from man to mouse with IgG. Freeze-fracture electron microscopy of LEMS neuromuscular junctions has revealed a paucity of presynaptic membrane active zones. Thus, the active zones might be the targets of the pathogenic autoantibodies in LEMS. To test this assumption, freeze-fracture electron microscopic studies were done in mice injected with 10 mg of IgG daily from each of three LEMS patients and in control mice treated with normal IgG or no IgG. IgG from patients 1 and 2 impaired neuromuscular transmission in mice, but IgG from patient 3 failed to do so. After 52-69 days of treatment, diaphragm or anterior tibial muscles were removed and coded. Paired muscles from control mice and mice receiving LEMS IgG were studied 'blindly'. Satisfactory freeze-fracture replicas of 185 presynaptic membrane P-faces were analyzed by stereometric methods. In mice treated with LEMS IgG that was pathogenic by electrophysiologic criteria, there was a selective depletion of active zones and active-zone particles but not of other membrane particles and there was a concomitant increase of large membrane particles aggregated into clusters. These findings provide additional evidence that the active zones facilitate quantal transmitter release by nerve impulse, lend further support to the assumption that the active-zone particles are Ca2+ channels, and establish mediation of the membrane lesions in LEMS by IgG.
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U2 - 10.1073/pnas.80.24.7636
DO - 10.1073/pnas.80.24.7636
M3 - Article
C2 - 6584877
AN - SCOPUS:0021076733
SN - 0027-8424
VL - 80
SP - 7636
EP - 7640
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 24 I
ER -