Pharmacology of α-Conotoxin MII-Sensitive Subtypes of Nicotinic Acetylcholine Receptors Isolated by Breeding of Null Mutant Mice

• DOI: 10.1124/mol.106.031492
• Publication Date: 2007-03-07T03:24:57Z
• Authors: Outi Salminen; Jennifer A. Drapeau; J. Michael McIntosh; Allan C. Collins; Michael J. Marks; Sharon R. Grady
• Keywords: Cytisine; Epibatidine; Alpha (finance)

Subtypes of nicotinic acetylcholine receptors (nAChR) containing α6 subunits comprise 25 to 30% the presynaptic nAChRs expressed in striatal dopaminergic terminals rodents and 70% monkeys. This class receptors, potentially important nicotine addiction, binds α-conotoxin MII (α-CtxMII) with high affinity is heterogeneous, consisting several subtypes mice, possibly an consideration for design compounds that selectively activate or antagonize subclass nAChRs. Selected-null mutant mice were bred generate isolated α6β2* vivo assessing pharmacology Binding membranes function synaptosomes from (α4–/–)(β3+/+) (α4–/–)(β3–/–) measured compared wild-type (α4+/+)(β3+/+) mice. Gene deletions (α4 β3) decreased binding ¹²⁵I-α-CtxMII without affecting α-CtxMII inhibition by epibatidine nicotine. Deletion α4 subunit substantially increased EC₅₀ values both nicotine- cytisine-stimulated α-CtxMII-sensitive dopamine release synaptosomes. A further increase was seen upon additional deletion β3 subunit. The data indicate one nAChR subtype, prevalent on terminals, has lowest a nicotine-mediated so far In conclusion, gene strategy enabled isolation α6* subtypes, these exhibited differential activation cytisine.