Anti-GQ1b antibodies and evoked acetylcholine release at mouse motor endplates

Miller Fisher syndrome (MFS) is clinically characterized by ataxia, areflex ia, and ophthalmoplegia, and is associated with serum anti-GQ1b-ganglioside antibodies. We have previously shown that anti-GQ1b antibodies induce comp lement-dependent, alpha-latrotoxin-like effects at mouse neuromuscular junc tions (NMJs) in vitro. This effect comprises a massive increase in spontane ous quantal acetylcholine (ACh) release, accompanied by block of evoked rel ease and muscle paralysis. This mechanism may contribute to the motor featu res of MFS. Whether the block of evoked ACh release is a primary effect of anti-GQ1b antibodies or occurs secondary to massive complement-dependent sp ontaneous release is unknown. Using conventional micro-electrode methods, w e measured in detail ACh release evoked with low- and high-rate nerve stimu lation, and studied the effect on it of a purified MFS IgG and a mouse mono clonal anti-GQ1b IgM (without added complement). We found that evoked trans mitter release was unaffected. Control experiments proved binding of anti-G Q1b antibody at the NMJ. We conclude that the block of nerve-evoked ACh rel ease at the NMJ is not a primary effect of anti-GQ1b antibodies, but is dep endent on antibody-mediated complement activation. It remains to be determi ned whether the block of nerve-evoked ACh release is the consequence of mas sive spontaneous ACh release or occurs as a concomitant event. (C) 2000 Joh n Wiley & Sons, Inc.