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 voltage-gated calcium channels (L-type and P-type), but others do not support these findings.


METHODS
Regulated secretion of tritiated dopamine ([3H]DA) in PC12 cells is mediated exclusively by calcium entry through L-type calcium channels. To examine whether purified ALS immunoglobulin G (IgG) inhibits [3H]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 [3H]DA release (32+/-4%) was observed by purified IgG from ALS patients compared with control subjects (11+/-2%; p < 0.01). Significant inhibition by IgG occurred in 79% (15/19) of the ALS patients compared with only 29% (5/17) in the control group (p < 0.01). The level of calcium channel inhibition by ALS IgG correlated positively with disease duration (r = 0.68; p < 0.01) and correlated negatively with age (r = -0.48; p < 0.05).


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.
Offen
D
D
Department of Neurology, Rabin Medical Center-Beilinson Campus, Sackler School of Medicine, Tel-Aviv University, Petah-Tikva, Israel.
Halevi
S
S
Orion
D
D
Mosberg
R
R
Stern-Goldberg
H
H
Melamed
E
E
Atlas
D
D
D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000494:pharmacology*; D015220:Calcium Channels / Q000276:immunology* / Q000378:metabolism; D020746:Calcium Channels, L-Type; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology*; D008564:Membrane Potentials / Q000276:immunology; D008875:Middle Aged; D009124:Muscle Proteins / Q000276:immunology / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D014316:Tritium
D001323:Autoantibodies; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007074:Immunoglobulin G; D009124:Muscle Proteins; D014316:Tritium; D004298:Dopamine