α-Conotoxin IMI exhibits subtype-specific nicotinic acetylcholine receptor blockade: Preferential inhibition of homomeric α7 and α9 receptors

Through a study of cloned nicotinic receptors expressed in Xenopus oocytes, we provide evidence that α-conotoxin IMI, a peptide marine snail toxin that induces seizures in rodents, selectively blocks subtypes of nicotinic acetylcholine receptors. α-Conotoxin IMI blocks homomeric α7 nicotinic receptors with the highest apparent affinity and homomeric α9 receptors with 8-fold lower affinity. This toxin has no effect on receptors composed of α2β2, α3β2, α4β2, α2β4, α3β4, or α4β4 subunit combinations. In contrast to α-bungarotoxin, which has high affinity for α7, α9, and α1β1γδ receptors, α-conotoxin IMI has low affinity for the muscle nAChR. Related Conus peptides, α-conotoxins MI and GI, exhibit a distinct specificity, strictly targeting the muscle subtype receptor but not α7 or α9 receptors. α-Conotoxins thus represent selective tools for the study of neuronal nicotinic acetylcholine receptors.