α-Conotoxin BuIA

α-Conotoxin BuIA is a 13 amino acid peptidyl toxin that was originally isolated from the fish-eating snail, Conus bullatus¹. This toxin exhibits strong antagonistic activity at α6/α3β2β3, α3β2, and α3β4 nicotinic acetylcholine receptors (nAChRs) and has the unique ability to kinetically discriminate between the β2 and β4-containing receptor subtypes, as the off-rates are rapid for β2-subunit, but very slow for β4-containing nAChRs. α-Conotoxin BuIA is a member of the A-superfamily of conotoxins and possess an unusual 4/4 disulfide scaffold. This toxin appears to be a valuable probe to distinguish among nAChRs containing different α and β subunits^1-4.

nAChRs are pentameric ligand-gated ion channels that are critically important for neuronal survival and cognitive function, as well as regulation of neurodegenerative diseases, including Alzheimer’s and Parkinson’s. The nAChR subtypes share a common basic structure, but their biophysical and pharmacological properties depend on their subunit composition. Thus, the subunit makeup of the nAChR subtypes is central to understanding their function in the nervous system and for discovering new subtype-selective drugs^5-7.