THE PHYSIOLOGICAL EFFECT OF ANTI-GM1 ANTIBODIES ON SALTATORY CONDUCTION AND TRANSMEMBRANE CURRENTS IN SINGLE MOTOR AXONS

Anti-ganglioside (anti-GM1) antibodies have been implicated in the pat hogenesis of Guillain-Barre syndrome, multifocal motor neuropathy and motor neuron diseases. It has been held that they may interfere with s altatory conduction by blocking sodium channels. We tested this hypoth esis by analysing action potentials from 140 single nerve fibres in 22 rat ventral roots using external longitudinal current measurement. Hi gh-titre anti-GM1 sera from Guillain-Barre syndrome or multifocal moto r neuropathy patients, or anti-GM1 rabbit sera were applied to the rat ventral root, where saltatory conduction in single motor fibres was s erially observed for 4-12 h (mean 8.2 h). For control experiments, we also tested anti-galactocerebroside (anti-GalC) sera, which causes acu te demyelinative conduction block, and tetrodotoxin (TTX), a sodium ch annel blocker Conduction block was found in 82% of the fibres treated with anti-GalC sera and 100% treated with TTX, but only in 2% (one out of 44) treated with the patients' sera and 5% (two out of 38) treated with rabbit anti-GM1 sera. All the nodes blocked by anti-GM1 sera rev ealed intense passive outward membrane current, in the internode just beyond the last active node. This pattern of current flow was similar to that in fibres blocked by demyelination with anti-GalC sera, and qu ite different from that seen in fibres blocked by reducing sodium curr ents with TTX. Our findings suggest that anti-GM1 sera neither mediate conduction black not-block sodium channels on their own We conclude t hat physiological action of the antibody alone is insufficient to expl ain clinically observed conduction block in human diseases.