Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using .omega.-conotoxin from Conus magus venom

Abstract

The .omega.-conotoxins from the venom of fish-hunting cone snails are probably the most useful of presently available ligands for neuronal Ca channels from vertebrates. Two of these peptide toxins, .omega.-conotoxins MVIIA and MVIIB from the venom of Conus magus, were purified. The amino acid sequences show significant differences from .omega.-conotoxins from Conus geographus. Total synthesis of .omega.-conotoxin MVIIA was achieved, and biologically active radiolabeled toxin was produced by iodination. Although .omega.-conotoxins from C. geographus (GVIA) and C. magus (MVIIA) appear to compete for the same sites in mammalian brain, in amphibian brain the high-affinity binding of .omega.-conotoxin MVIIA has narrower specificity. In this system, it is demonstrated that a combination of two .omega.-conotoxins can be used for biochemically defining receptor subtypes and suggested that these correspond to subtypes of neuronal Ca2+ channels.