Alpha-synuclein potentiates Ca2+ influx through voltage-dependent Ca2+ channels

Alpha-synuclein localized in synaptic terminals plays an important role in the pathogenesis of neurodegenerative diseases. The central domain of the protein, the nonamyloid component, is probably responsible for a-synuclein toxicity. Here, we report that a-synuclein and its nonamyloid component induced Ca2+ influx in rat synaptoneurosomes. The effect of alpha-synuclein was eliminated by the N-type specific Ca2+ channel blocker, omega-conotoxin GVIA. The antioxidant, resveratrol, and the nitric oxide synthase inhibitor, N-omega-nitro-L-arginine, did not prevent alpha-synuclein-incluced Ca2+ influx. Our findings indicate that a-synuclein stimulated Ca2+ influx through N-type voltage-dependent Ca2+ channels by a mechanism other than free radicals. A direct interaction between a-synuclein and N-type Ca2+ channels could be responsible for their effects on Ca2+ influx through voltage-dependent Ca2+ channels.