alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors.

Abstract

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.

• Authors: D S Johnson, J Martinez, A B Elgoyhen, S F Heinemann, J M McIntosh
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 48 Issue 2 Pg. 194-9 (Aug 1995) ISSN: 0026-895X [Print] United States
• PMID: 7651351 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bungarotoxins
• Conotoxins
• Mollusk Venoms
• Nicotinic Antagonists
• Oligopeptides
• Receptors, Nicotinic
• alpha-conotoxin ImI

Topics

• Amino Acid Sequence
• Animals
• Bungarotoxins (pharmacology)
• Cloning, Molecular
• Conotoxins
• Injections, Intraventricular
• Molecular Sequence Data
• Mollusk Venoms (chemistry)
• Nicotinic Antagonists
• Oligopeptides (administration & dosage, chemistry, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Nicotinic (genetics)
• Xenopus