ALPHA-CONOTOXIN IM(I) EXHIBITS SUBTYPE-SPECIFIC NICOTINIC ACETYLCHOLINE-RECEPTOR BLOCKADE - PREFERENTIAL INHIBITION OF HOMOMERIC ALPHA-7 AND ALPHA-9 RECEPTORS

Through a study of cloned nicotinic receptors expressed in Xenopus ooc ytes, we provide evidence that alpha-conotoxin ImI, a peptide marine s nail toxin that induces seizures in rodents, selectively blocks subtyp es of nicotinic acetylcholine receptors. alpha-Conotoxin ImI blocks ho momeric alpha 7 nicotinic receptors with the highest apparent affinity and homomeric alpha 9 receptors with 8-fold lower affinity. This toxi n has no effect on receptors composed of alpha 2 beta 2, alpha 3 beta 2, alpha 4 beta 2, alpha 2 beta 4, alpha 3 beta 4, or alpha 4 beta 4 s ubunit combinations. In contrast to alpha-bungarotoxin, which has high affinity for alpha 7, alpha 9, and alpha 1 beta 1 gamma delta recepto rs, alpha-conotoxin ImI has low affinity for the muscle nAChR. Related Conus peptides, alpha-conotoxins MI and GI, exhibit a distinct specif icity, strictly targeting the muscle subtype receptor but not alpha 7 or alpha 9 receptors. alpha-Conotoxins thus represent selective tools for the study of neuronal nicotinic acetylcholine receptors.