Peptides from Conus Venoms which Affect Ca⁺⁺ Entry into Neurons

Abstract

The venoms of fish-hunting Conus contain paralytic conotoxins and an unprecedented variety of other biologically-active peptides. Particularly noteworthy are peptides which inhibit calcium entry into neurons, the conantokins and w-conotoxins which target NMDA receptors and voltage-sensitive Ca channels respectively.

The conantokins contain at least four residues of γ-carboxyglutamate (Gla), a post-translationally modified amino acid. Conantokins are folded into an α-helical conformation and bind acidic membranes in a calcium-dependent manner. Upon envenomation, conantokins may concentrate on appropriate membranes and target to peripheral fish NMDA receptors located on such membranes.

The w-conotoxins are disulfide bonded peptides; a comparison of several w-conotoxin sequences reveals considerable sequence variability. Recent studies with w-conotoxins have also revealed a developmental specificity in mice. The results suggest that elements controlling breathing in neonatal mammals, but not in adults, are w-conotoxin sensitive.