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

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Abstract
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.