Antibodies against GM1 ganglioside affect K+ and Na+ currents in isolated rat myelinated nerve fibers.
High titers of anti-GM1 ganglioside antibodies (anti-GM1 antibodies) may be implicated in lower motor neuron disease. We studied the pathogenic role of anti-GM1 antibody using the petroleum jelly-gap voltage clamp technique on isolated single myelinated rat nerve fibers. Anti-GM1 antisera were obtained from rabbits immunized with GM1 ganglioside. Extracellularly applied anti-GM1 antisera without complement activity increased both the rate of rise and the amplitude of the K+ current elicited by step depolarization, with little effect on Na+ current. In the presence of active complement, however, anti-GM1 antibodies decreased the Na+ current, and caused a progressive increase of nonspecific leakage current. Neither complement alone nor complement-supplemented antisera from which anti-GM1 antibodies were depleted by affinity chromatography had any effect on ionic current. These observations indicate that anti-GM1 antibodies themselves can uncover K+ channels in the paranodal region, while anti-GM1 antibodies bound to the nodal membrane in the presence of complement may form antibody-complement complexes that block Na+ channels and disrupt the membrane at the node of Ranvier.
Takigawa
T
T
Third Department of Medicine, Shiga University of Medical Science, Japan.
Yasuda
H
H
Kikkawa
R
R
Shigeta
Y
Y
Saida
T
T
Kitasato
H
H
D000200:Action Potentials / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D005677:G(M1) Ganglioside / Q000276:immunology*; D066298:In Vitro Techniques; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000276:immunology*; D015221:Potassium Channels / Q000276:immunology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000276:immunology*
D000906:Antibodies; D015221:Potassium Channels; D015222:Sodium Channels; D005677:G(M1) Ganglioside