Calcium channel antagonists. Omega-conotoxin defines a new high affinity site

The omega-conotoxins, a class of Ca2+ channel antagonists from fish-hunting marine snails, have recently been described (Olivera, B. M., McIntosh, J. M., Zeikus, R., Gray, W. R., Varga, J., Rivier, J., de Santos, V., and Cruz, L. J. (1985) Science, 230, 1338-1343). One of these peptide neurotoxins, omega-conotoxin GVIA, was radiolabeled with iodine, and the 125I-labeled toxin was shown to bind specifically to high affinity sites on chick brain synaptosomes. The toxin-receptor complex was extremely stable; addition of an excess of unlabeled toxin did not cause significant displacement of the labeled toxin after 2 h. Binding competition data suggest that omega-conotoxin defines a new high affinity receptor site affecting voltage-activated Ca2+ channels, distinct from both the verapamil and dihydropyridine target sites.