Antibodies against GM1 ganglioside affect K+ and NA+ currents in isolated rat myelinated nerve fibers

Abstract

High titers of anti‐GM 1 ganglioside antibodies (anti‐GM 1 antibodies) may be implicated in lower motor neuron disease. We studied the pathogenic role of anti‐GM 1 antibody using the petroleum jelly–gap voltage clamp technique on isolated single myelinated rat nerve fibers. Anti‐GM 1 antisera were obtained from rabbits immunized with GM 1 ganglioside. Extracellularly applied anti‐GM 1 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‐GM 1 antibodies decreased the Na+ current, and caused a progressive increase of nonspecific leakage current. Neither complement alone nor complement‐supplemented antisera from which anti‐GM 1 antibodies were depleted by affinity chromatography had any effect on ionic current. These observations indicate that anti‐GM 1 antibodies themselves can uncover K+ channels in the paranodal region, while anti‐GM 1 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.