title: The physiological effect of anti-GM1 antibodies on saltatory conduction and transmembrane currents in single motor axons.
abstract: Anti-ganglioside (anti-GM1) antibodies have been implicated in the pathogenesis of Guillain-Barré syndrome, multifocal motor neuropathy and motor neuron diseases. It has been held that they may interfere with saltatory conduction by blocking sodium channels. We tested this hypothesis by analysing action potentials from 140 single nerve fibres in 22 rat ventral roots using external longitudinal current measurement. High-titre anti-GM1 sera from Guillain-Barré syndrome or multifocal motor neuropathy patients, or anti-GM1 rabbit sera were applied to the rat ventral root, where saltatory conduction in single motor fibres was serially observed for 4-12 h (mean 8.2 h). For control experiments, we also tested anti-galactocerebroside (anti-GalC) sera, which causes acute demyelinative conduction block, and tetrodotoxin (TTX), a sodium channel 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 revealed 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 quite different from that seen in fibres blocked by reducing sodium currents with TTX. Our findings suggest that anti-GM1 sera neither mediate conduction block nor block sodium channels on their own. We conclude that physiological action of the antibody alone is insufficient to explain clinically observed conduction block in human diseases.
authors.affiliation: Department of Neurology, Kyoto University School of Medicine, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hirota
authors.forename: R
authors.initials: R
authors.lastname: Kaji
authors.forename: H
authors.initials: H
authors.lastname: Bostock
authors.forename: K
authors.initials: K
authors.lastname: Shindo
authors.forename: T
authors.initials: T
authors.lastname: Kawasaki
authors.forename: K
authors.initials: K
authors.lastname: Mizutani
authors.forename: N
authors.initials: N
authors.lastname: Oka
authors.forename: N
authors.initials: N
authors.lastname: Kohara
authors.forename: T
authors.initials: T
authors.lastname: Saida
authors.forename: J
authors.initials: J
authors.lastname: Kimura
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D001369:Axons / Q000502:physiology*; D005677:G(M1) Ganglioside / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D008564:Membrane Potentials / Q000502:physiology; D016472:Motor Neuron Disease / Q000276:immunology; D009046:Motor Neurons / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology*; D011129:Polyradiculoneuropathy / Q000276:immunology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D026941:Sodium Channel Blockers; D005677:G(M1) Ganglioside; D013779:Tetrodotoxin