alpha-Conotoxins as selective probes for nicotinic acetylcholine receptor subclasses

alpha-Conotoxins are selective antagonists of neuromuscular or neuronal nicotinic acetylcholine receptors. Individual family members are often highly selective towards distinct receptor subclasses, most notably within neuronal nicotinic acetylcholine receptors. As such they are being used as tools to probe for the type and diversity of receptor subclasses in distinct parts of the central and peripheral nervous systems. Many new alpha-conotoxins are being identified every year, broadening the available armoury because small variations in their sequences and structures often confer altered selectivity towards receptor subunits and subclasses. Many neurological diseases are being associated wholly or in part with functional changes within specific subclasses of nicotinic acetylcholine receptors. Significantly, with more structures of alpha-conotoxins also becoming available this enables ready comparison of their similarities and, more notably, of their subtle differences, which dictate subclass selectivity. As such, alpha-conotoxins offer the potential to become templates for the creation, through rational drug design strategies, of pharmaceuticals highly selective for specific subclasses of nicotinic acetylcholine receptors.