Concanavalin a inhibits pathophysiological effects of anti-ganglioside GQ1b antibodies at the mouse neuromuscular synapse

Anti‐GQ1b antibodies are present in the Miller Fisher syndrome (MFS), a monophasic neuropathy characterized by ataxia, areflexia, ophthalmoplegia, and sometimes cranial muscle weakness. We have previously shown, at the mouse neuromuscular junction (NMJ) ex vivo, that anti‐GQ1b antibodies, through complement classic pathway activation, block synaptic transmission in a way that resembles the effect of the pore‐forming α‐latrotoxin (αLTx). In order to clarify the mechanism of these αLTx‐like effects, including possible involvement of the alternative and mannose‐binding protein complement pathways, we studied the effects of concanavalin A (ConA), a lectin known to block the action of αLTx, immunoglobulins, and early complement components. With electrophysiological, immunohistological, and bioassay experiments, we showed that the αLTx‐like effects of anti‐GQ1b antibody and complement were inhibited by pre‐ and coincubation with ConA. However, ConA was not able to inhibit evolution of αLTx‐like effects when coincubated upon addition of complement at NMJs that had already bound anti‐GQ1b antibody. Our data suggest that the mannose‐binding protein pathway is not involved in the αLTx‐like effect and that the inhibiting effect of ConA principally arises through interference with presynaptic binding of anti‐GQ1b antibody. In control experiments, ConA prevented the neuroexocytotic effects of αLTx, indicating that αLTx receptors were inhibited under these conditions. We conclude that, although the physiological effects at the NMJ of anti‐GQ1b antibody and αLTx are very similar, the activity of anti‐GQ1b antibody is not mediated through activation of αLTx receptors, but rather is caused by direct presynaptic membrane damage through classic complement pathway activation. Muscle Nerve, 2005