Presynaptic changes of neuromuscular transmission in mice induced by passive transfer of plasma with anti-presynaptic membrane receptor antibodies from a patient with myasthenia gravis.
Electrophysiological studies were conducted in three groups of mice to determine the possible involvement of the antibodies to presynaptic membrane receptor (PsmR), a beta-bungarotoxin (beta-BuTX) binding protein, in the pathogenesis of myasthenia gravis (MG). Mice were untreated (untreated group, n = 8) or were injected (i.p.) with blood plasma from a MG patient, which contained antibodies to PsmR, at a dose of 1 ml per day for more than 2 months (MG plasma group, n = 12) or with plasma from healthy subjects (normal plasma group, n = 10). Prior to plasma injection, cyclophosphamide was given at 300 mg/kg (i.p.) to all three groups. About three weeks after plasma injection, most mice of the MG plasma group became less mobile in comparison with those of the two control groups. Electrophysiological recording showed three main changes in the MG plasma group: (1) the increase in the frequency of miniature endplate potentials (mEPPs) induced by Krebs solution with high K+ concentration (17.5 mM) was significantly lowered, which was confirmed in mice injected with IgG (50 mg per day) from this patient for two days; (2) the quantal content of EPP was decreased; and (3) the decrement in the amplitude of a train EPP (50 Hz) was quickened. Our results suggest that this experimental model is different from that of Lambert-Eaton myasthenic syndrome and that antibodies to PsmR may also be involved in the pathogenesis of MG.
Xu
K
K
Shanghai Institute of Physiology, Chinese Academy of Sciences, China.
Shu
X Q
XQ
Zhuo
X L
XL
Lu
C Z
CZ
D000818:Animals; D000906:Antibodies / Q000097:blood*; D001522:Behavior, Animal; D001803:Blood Transfusion; D004594:Electrophysiology; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009045:Motor Endplate / Q000502:physiology; D009157:Myasthenia Gravis / Q000097:blood*; D009469:Neuromuscular Junction / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D009435:Synaptic Transmission / Q000502:physiology*
D000906:Antibodies; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface