Lambert-Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones.
In the freeze-fractured presynaptic membrane of the motor end-plate, the active zones consist of two parallel arrays and each array contains 10- to 12-nm particles arranged in two rows. In the Lambert-Eaton myasthenic syndrome (LEMS) and in mice treated with 10 mg/day of LEMS IgG, administered intraperitoneally for several weeks, there was a paucity and disorganization of the active zones, and clusters of 10- to 12-nm particles appeared. To further define the changes in the active zones, mice were studied that had been treated over 2 days with 104 to 180 mg of IgG. Treatment transferred the physiological defect of LEMS. Control mice received normal human IgG or no IgG. The spacing and density (number/unit area) of active-zone particles were evaluated in presynaptic membrane P-faces using computer-assisted stereometry. In the normal active zone, the distance between particles in a given row and between adjacent rows of an array was less than, but the distance between the two arrays was greater than, the distance between the two antigen-binding sites on human IgG. In mice treated with LEMS IgG, the initial alteration in the active zone was a decrease in the distance between particles in a given row and between adjacent rows of an array; the distance between the two arrays remained unaltered. In more affected active zones, the parallel orientation of the rows was disturbed and the arrays became clusters. There was a significantly reduced density of active zones and of large-membrane particles associated with all active zones and clusters.(ABSTRACT TRUNCATED AT 250 WORDS)
Fukuoka
T
T
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Engel
A G
AG
Lang
B
B
Newsom-Davis
J
J
Prior
C
C
Wray
D W
DW
D000818:Animals; D005614:Freeze Fracturing; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009045:Motor Endplate / Q000187:drug effects / Q000648:ultrastructure; D009135:Muscular Diseases / Q000097:blood / Q000473:pathology*; D013570:Synaptic Membranes / Q000187:drug effects* / Q000648:ultrastructure; D013577:Syndrome
D007074:Immunoglobulin G