α-conotoxin Bt1.8 (Bt1.8) is a 16 amino acid peptidyl toxin originally cloned from the venom duct of the worm-hunting cone snail, Conus betulinus¹. This toxin potently and selectively blocks neuronal α6/α3β2β3 and α3β2 nicotinic acetylcholine receptors (nAChRs), with IC₅₀ values of 2.1 nM and 9.4 nM, respectively¹. Bt1.8 belongs to the α4/7-CTx subfamily that primarily targets the vertebrate neuronal nAChRs.

Neuronal nAChRs are a heterogeneous family of ligand-gated cation channels that are expressed throughout the brain and involved in a wide range of physiological and pathophysiological processes. These distinct receptor subtypes have a pentameric structure consisting of a homomeric or heteromeric combination of 12 different subunits (α2–α10, β2–β4)².

nAChRs 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^2-4.