Conus Peptides Targeted to Specific Nicotinic Acetylcholine Receptor Subtypes

The venoms of predatory cone snails represent a rich combinatorial-like library of evolutionarily selected, neuropharmacologically active peptides. A major fraction of the venom components are conotoxins—small, disulfide-rich peptides that potently and specifically target components of the neuromuscular system, particularly ligand- and voltage-gated ion channels. This review focuses on Conus peptides, which act at nicotinic acetylcholine receptors. These nicotinic antagonist peptides from Conus are broadly divided into two groups: those that act at the neuromuscular junction and those that act at subtypes of neuronal nicotinic acetylcholine receptors. The latter include peptides specific for the α7, α3β2, and α3β4 nicotinic receptor subtypes. The degree of specificity exhibited by these peptides is remarkable, particularly given their relatively small size. As a group the nicotinic acetylcholine receptor-targeted Conus peptides represent an increasingly well-defined set of tools for probing the structure, function, and physiological role of nicotinic acetylcholine receptors.