Antibodies from ALS patients inhibit dopamine release mediated by L-type calcium channels

Objective: To examine the presence of anti-L-type calcium channel antibodies in the serum of ALS patients. Background: Autoimmunity has been hypothesized as one of the mechanisms underlying the pathogenesis of sporadic ALS. Previous studies reported that sera from patients with sporadic ALS contain antibodies against voltagegated calcium channels (L-type and P-type), but others do not support these findings. Methods: Regulated secretion of tritiated dopamine ([ 3 H]DA) in PC12 cells in mediated exclusively by calcium entry through L-type calcium channels. To examine whether purified ALS immunoglobulin G (IgG) inhibits [ 3 H]DA release by interfering with calcium entry through L-type calcium channels, evoked release in PC12 cells was determined in the presence of ALS IgG. This functional assay provides a sensitive way to examine L-type calcium channel interaction with IgG from ALS patients. Results: A significant inhibition of depolarization-evoked [ 3 H]DA release (32 ± 4%) was observed by purified IgG from ALS patients compared with control subjects (11 ± 2%; p p r = 0.68; p r = -0.48; p Conclusions: These results confirm the presence of antibodies against the L-type calcium channel in the majority of sera from ALS patients, supporting their role in the pathogenesis of ALS.