Interactions between the presynaptically active neurotoxins α-latrotoxin and ω-conotoxin GVIA: studies on calcium fluxes and binding parameters in rat and chicken synaptosomes

Abstract

Possible interactions between α-latrotoxin, an activator of synaptosomal calcium uptake, and ω-conotoxin GVIA, an inhibitor of voltage-sensitive calcium channels of the N-type, were investigated in rat and chicken synaptosomal preparations. While ω-conotoxin GVIA potently and effectively inhibited calcium uptake induced by elevated potassium in chick synaptosomes, little or no effect of ω-conotoxin GVIA was observed either in potassium-treated rat synaptosomes or in α-latrotoxin-exposed synaptosomes of either species. In contrast to the lack of effect of ω-conotoxin on stimulated calcium uptake in rat synaptosomes, cadmium effectively inhibited calcium uptake induced by either potassium or α-latrotoxin. Synaptosomal calcium transport induced by α-latrotoxin can be bidirectional, since α-latrotoxin also induced efflux of preaccumulated calcium. Competition experiments revealed that binding of ¹²⁵I-labelled ω-conotoxin and ¹²⁵I-labelled α-latrotoxin was similar in either chicken or rat synaptosomes. Neither α-latrotoxin nor ω-conotoxin competed with the binding of the other ligand in either species. The results reported here show that (1) elevated potassium evokes calcium uptake principally through N-channels in avian but not in rat synaptosomes; (2) α-latrotoxin-activated calcium fluxes are ω-conotoxin insensitive but cadmium sensitive; (3) the molecular acceptors for the two ligands are likely to be unrelated synaptic membrane constituents.Key words: synaptosomαes, calcium, α-latrotoxin, ω-conotoxin.