Properties of structure and interaction of the receptor for omega-conotoxin, a polypeptide active on Ca2+ channels.

Binding properties of omega-conotoxin (GVIA) to avian and mammalian neuronal Ca2+ channels were investigated using a radioiodinated toxin derivative. An exceptionally high affinity of 0.6 to 2 pM was found both from equilibrium and kinetics measurements. Only one class of non-interacting binding sites was detected. In chick brain, dissucinimidyl suberate specifically cross-linked the toxin to 170 kDa component that comprises a 140 kDa peptide disulfide linked to a 30 kDa peptide, very similar to the heavily glycosylated component of the L-type DHP-sensitive Ca2+ channel. A large peptide of 210-220 kDa was labelled using the azidonitrobenzoyloxy derivative of omega-conotoxin as cross-linking reagent but not the 170/140+30 kDa component. The results suggest that the neuronal Ca2+ channel could be composed by the association of two distinct high molecular weight peptides of 220 kDa and 170/140+30 kDa.