T. Takigawa et al., ANTIBODIES AGAINST GM(1) GANGLIOSIDE AFFECT K-FIBERS( AND NA+ CURRENTS IN ISOLATED RAT MYELINATED NERVE), Annals of neurology, 37(4), 1995, pp. 436-442
High titers of anti-GM(1) ganglioside antibodies (anti-GM(1) antibodie
s) may be implicated in lower motor neuron disease. We studied the pat
hogenic role of anti-GM(1) antibody using the petroleum jelly-gap volt
age clamp technique on isolated single myelinated rat nerve fibers. An
ti-GM(1) antisera were obtained from rabbits immunized with GM(1) gang
lioside. Extracellularly applied anti-GM(1) antisera without complemen
t activity increased both the rate of rise and the amplitude of the K current elicited by step depolarization, with little effect on Na+ cu
rrent. In the presence of active complement, however, anti-GM(1) antib
odies decreased the Na+ current, and caused a progressive increase of
nonspecific leakage current. Neither complement alone nor complement-s
upplemented antisera from which anti-GM(1) antibodies were depleted by
affinity chromatography had any effect on ionic current. These observ
ations indicate that anti-GM(1) antibodies themselves can uncover K+ c
hannels in the paranodal region, while anti-GM(1) antibodies bound to
the nodal membrane in the presence of complement may form antibody-com
plement complexes that block Na+ channels and disrupt the membrane at
the node of Ranvier.