ALS IgGs suppress [Ca2+]i rise through P/Q-type calcium channels in central neurones in culture.
Confocal laser scanning microscopy (with the fluorescent calcium dye fluo-3) was used to test the effect of IgG obtained from patients with amyotrophic lateral sclerosis (ALS) on the KCl-induced [Ca2+] rise in rat hippocampal neurones in culture. In the presence of tetrodotoxin and ionotropic glutamate receptor antagonists, ALS IgGs depressed (by 30-40%) Ca2+ transients evoked by influx of Ca2+ through voltage-activated channels; such an effect did not occur with IgG obtained from healthy donors. The depressant action of ALS IgG was selectively prevented by the inhibitor of P/Q-type Ca2+ channels, omega-agatoxin IVA (which alone reduced Ca2+ transients by 40%). The reduced Ca2+ transients might impair Ca(2+)-dependent glutamate receptor desensitization and thus facilitate excitotoxic damage.
International School for Advanced Studies (SISSA), Trieste, Italy.
P R
PR
Andjus
L
L
Khiroug
A
A
Nistri
E
E
Cherubini
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007074:Immunoglobulin G / Q000494:pharmacology*; D051381:Rats
D015220:Calcium Channels; D007074:Immunoglobulin G; D002118:Calcium