Interactions between the presynaptically active neurotoxins alpha-latrotoxin and omega-conotoxin GVIA: studies on calcium fluxes and binding parameters in rat and chicken synaptosomes.
Possible interactions between alpha-latrotoxin, an activator of synaptosomal calcium uptake, and omega-conotoxin GVIA, an inhibitor of voltage-sensitive calcium channels of the N-type, were investigated in rat and chicken synaptosomal preparations. While omega-conotoxin GVIA potently and effectively inhibited calcium uptake induced by elevated potassium in chick synaptosomes, little or no effect of omega-conotoxin GVIA was observed either in potassium-treated rat synaptosomes or in alpha-latrotoxin-exposed synaptosomes of either spaces. In contrast to the lack of effect of omega-conotoxin on stimulated calcium uptake in rat synaptosomes, cadmium effectively inhibited calcium uptake induced by either potassium or alpha-latrotoxin. Synaptosomal calcium transport induced by alpha-latrotoxin can be bidirectional, since alpha-latrotoxin also induced efflux of preaccumulated calcium. Competition experiments revealed that binding of 125I-labelled omega-conotoxin and 125I-labelled alpha-latrotoxin was similar in either chicken or rat synaptosomes. Neither alpha-latrotoxin nor omega-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) alpha-latrotoxin-activated calcium fluxes are omega-conotoxin insensitive but cadmium sensitive; (3) the molecular acceptors for the two ligands are likely to be unrelated synaptic membrane constituents.
Scheer
H W
HW
Department of Pharmacology, University of Montréal, Qué., Canada.
D000818:Animals; D001180:Arthropod Venoms / Q000633:toxicity*; D002104:Cadmium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002645:Chickens; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D009498:Neurotoxins / Q000633:toxicity*; D010456:Peptides, Cyclic / Q000633:toxicity*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013111:Spider Venoms / Q000633:toxicity*; D013569:Synapses / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D001180:Arthropod Venoms; D002132:Calcium Radioisotopes; D007457:Iodine Radioisotopes; D009498:Neurotoxins; D010456:Peptides, Cyclic; D013111:Spider Venoms; D002104:Cadmium; C020763:alpha-latrotoxin; D020866:omega-Conotoxin GVIA; D011188:Potassium; D002118:Calcium