ALS IgGs suppress [Ca²⁺](i) rise through P/Q-type calcium channels in central neurones in culture

Abstract

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+](i) 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, ω-agatoxin IVA (which alone reduced Ca2+ transients by 40%). The reduced Ca2+ transients might impair Ca2+-dependent glutamate receptor desensitization and thus facilitate excitotoxic damage.