alpha-Conotoxin ImI 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 oocytes, we provide evidence that alpha-conotoxin ImI, a peptide marine snail toxin that induces seizures in rodents, selectively blocks subtypes of nicotinic acetylcholine receptors. alpha-Conotoxin ImI blocks homomeric alpha 7 nicotinic receptors with the highest apparent affinity and homomeric alpha 9 receptors with 8-fold lower affinity. This toxin 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 subunit combinations. In contrast to alpha-bungarotoxin, which has high affinity for alpha 7, alpha 9, and alpha 1 beta 1 gamma delta receptors, alpha-conotoxin ImI has low affinity for the muscle nAChR. Related Conus peptides, alpha-conotoxins MI and GI, exhibit a distinct specificity, 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.
Johnson
D S
DS
Molecular Neurobiology Laboratory, Salk Institute, La Jolla, California 92037, USA.
Martinez
J
J
Elgoyhen
A B
AB
Heinemann
S F
SF
McIntosh
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D003001:Cloning, Molecular; D020916:Conotoxins; D007276:Injections, Intraventricular; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry*; D018733:Nicotinic Antagonists; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics; D014981:Xenopus
D002038:Bungarotoxins; D020916:Conotoxins; D008978:Mollusk Venoms; D018733:Nicotinic Antagonists; D009842:Oligopeptides; D011978:Receptors, Nicotinic; C087686:alpha-conotoxin ImI