Amyotrophic lateral sclerosis immunoglobulins are ineffective in altering calcium influx through presynaptic voltage-sensitive calcium channels.

Recent work has suggested that one factor in the etiology of the neuromuscular disease, amyotrophic lateral sclerosis (ALS), may be an autoimmune mechanism in which presynaptic voltage-sensitive calcium channels are an antigenic target. We have developed a fluorescence technique to measure rapid Ca2+ influx through presynaptic calcium channels in isolated nerve terminals (synaptosomes) from rat cerebral cortex. Depolarization of the synaptosomes by elevated external K+ concentration caused a rapid increase in cytoplasmic Ca2+, as measured by a change in fluorescence of the Ca2+ chelating dye, Fura-2, which was loaded inside the synaptosomes. Pharmacological characterization suggests that the P- and Q-subtypes of voltage-sensitive calcium channels mediate the majority of this Ca2+ influx. The synaptosome preparation has been used as a model system to investigate the effects of IgG, purified from eight ALS patients, on presynaptic calcium channel function. IgG (1 microgram ml-1 to 1 mg ml-1) was preincubated with the synaptosomes prior to depolarization. IgG, from these eight ALS patients, had no systematic effects on presynaptic Ca2+ influx. Thus, using this system, we find no evidence for an effect of ALS IgG on the function of presynaptic calcium channels.