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Received for publication February 11, 2005.
Revised March 3, 2005.
Accepted for publication March 4, 2005.
6-containing nicotinic acetylcholine receptors is selectively reduced, but not eliminated, by 
3 subunit gene deletion
mRNAs for the neuronal nicotinic receptor (nAChR) 
6 and 
3 subunits are abundantly expressed and colocalized in dopaminergic cells of the substantia nigra and ventral tegmental area. Studies using subunit-null mutant mice have shown that 6- or 3-dependent nAChRs bind -conotoxin MII (-CtxMII) with high affinity and modulate striatal dopamine release. This study explores the effects of 3 subunit-null mutation on striatal and midbrain nAChR expression, composition, and pharmacology. Ligand binding and immunoprecipitation experiments using subunit-specific antibodies indicated that 3-null mutation selectively reduced striatal 6* nAChR expression by 76% vs. 3+/+ control. Parallel experiments showed a smaller reduction in both midbrain 3* and 6* nAChRs (34% and 42% vs. 3+/+ control, respectively). Sedimentation coefficient determinations indicated that residual 6* nAChRs in 3-/- striatum were pentameric, like their wild-type counterparts. Immunoprecipitation experiments on immunopurified 3* nAChRs demonstrated that almost all wild-type striatal 3* nAChRs also contain 4, 6, and 2 subunits, although a small population of non-3 6* nAChRs is also expressed. 3 subunit incorporation appeared to increase 4 participation in 62* complexes. 125I-Epibatidine competition binding studies showed that the -CtxMII affinity of 6* nAChRs from the striata of 3-/- mice was similar to those isolated from 3+/+ animals. Taken together, the results of these experiments show that the 3 subunit is important for the correct assembly, stability and/or transport of 6* nAChRs in dopaminergic neurons, and influences their subunit composition. However, 3 subunit expression is not essential for the expression of 6*, high affinity -CtxMII-binding nAChRs.
Key words:
Nicotinic cholinergic, Ion channel regulation, Receptor binding studies
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