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

Abstract

Recent work has suggested that one factor in the etiology of the neuromuscular disease, amyotrophic lateral sclerosis (A LS), 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 Ca?+ 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 μg 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. [Neural Res 1997; 19: 129–134]