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 alpha-synuclein toxicity. Here, we report that alpha-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, Nomega-nitro-L-arginine, did not prevent alpha-synuclein-induced Ca2+ influx. Our findings indicate that alpha-synuclein stimulated Ca2+ influx through N-type voltage-dependent Ca2+ channels by a mechanism other than free radicals. A direct interaction between alpha-synuclein and N-type Ca2+ channels could be responsible for their effects on Ca2+ influx through voltage-dependent Ca2+ channels.
Adamczyk
Agata
A
Department of Cellular Signaling, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. agatazambrzycka@hotmail.com
Strosznajder
Joanna B
JB
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002247:Carbon Isotopes / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000648:ultrastructure; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000502:physiology; D051844:alpha-Synuclein / Q000494:pharmacology*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002247:Carbon Isotopes; D004791:Enzyme Inhibitors; D051844:alpha-Synuclein; D019335:Nitroarginine; D020866:omega-Conotoxin GVIA; D002118:Calcium