Anti-GQ1b antibodies and evoked acetylcholine release at mouse motor endplates.
Miller Fisher syndrome (MFS) is clinically characterized by ataxia, areflexia, and ophthalmoplegia, and is associated with serum anti-GQ1b-ganglioside antibodies. We have previously shown that anti-GQ1b antibodies induce complement-dependent, alpha-latrotoxin-like effects at mouse neuromuscular junctions (NMJs) in vitro. This effect comprises a massive increase in spontaneous quantal acetylcholine (ACh) release, accompanied by block of evoked release and muscle paralysis. This mechanism may contribute to the motor features of MFS. Whether the block of evoked ACh release is a primary effect of anti-GQ1b antibodies or occurs secondary to massive complement-dependent spontaneous release is unknown. Using conventional micro-electrode methods, we measured in detail ACh release evoked with low- and high-rate nerve stimulation, and studied the effect on it of a purified MFS IgG and a mouse monoclonal anti-GQ1b IgM (without added complement). We found that evoked transmitter release was unaffected. Control experiments proved binding of anti-GQ1b antibody at the NMJ. We conclude that the block of nerve-evoked ACh release at the NMJ is not a primary effect of anti-GQ1b antibodies, but is dependent on antibody-mediated complement activation. It remains to be determined whether the block of nerve-evoked ACh release is the consequence of massive spontaneous ACh release or occurs as a concomitant event.
Bullens
R W
RW
Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. R.W.M.Bullens@lumc.nl
O'Hanlon
G M
GM
Goodyear
C S
CS
Molenaar
P C
PC
Conner
J
J
Willison
H J
HJ
Plomp
J J
JJ
D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D003165:Complement System Proteins / Q000494:pharmacology; D004594:Electrophysiology; D019085:Fluorescent Antibody Technique, Direct; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008839:Microelectrodes; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007074:Immunoglobulin G; D009414:Nerve Growth Factors; C039129:GQ1b ganglioside; D003165:Complement System Proteins; D000109:Acetylcholine