RT Journal Article SR Electronic T1 Expression of Nigrostriatal α6-Containing Nicotinic Acetylcholine Receptors Is Selectively Reduced, but Not Eliminated, by β3 Subunit Gene Deletion JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 2007 OP 2015 DO 10.1124/mol.105.011940 VO 67 IS 6 A1 Cecilia Gotti A1 Milena Moretti A1 Francesco Clementi A1 Loredana Riganti A1 J. Michael McIntosh A1 Allan C. Collins A1 Michael J. Marks A1 Paul Whiteaker YR 2005 UL http://molpharm.aspetjournals.org/content/67/6/2007.abstract AB mRNAs for the neuronal nicotinic acetylcholine receptor (nAChR) α6 and β3 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 α6- or β3-dependent nAChRs bind α-conotoxin MII (α-CtxMII) with high affinity and modulate striatal dopamine release. This study explores the effects of β3 subunit-null mutation on striatal and midbrain nAChR expression, composition, and pharmacology. Ligand binding and immunoprecipitation experiments using subunit-specific antibodies indicated that β3-null mutation selectively reduced striatal α6* nAChR expression by 76% versus β3+/+ control. Parallel experiments showed a smaller reduction in both midbrain α3* and α6* nAChRs (34 and 42% versus β3+/+ control, respectively). Sedimentation coefficient determinations indicated that residual α6* nAChRs in β3–/– striatum were pentameric, like their wild-type counterparts. Immunoprecipitation experiments on immunopurified β3* nAChRs demonstrated that almost all wild-type striatal β3* nAChRs also contain α4, α6, and β2 subunits, although a small population of non-β3 α6* nAChRs is also expressed. β3 subunit incorporation seemed to increase α4 participation in α6β2* complexes. 125I-Epibatidine competition binding studies showed that the α-CtxMII affinity of α6* nAChRs from the striata of β3–/– mice was similar to those isolated from β3+/+ animals. Together, the results of these experiments show that the β3 subunit is important for the correct assembly, stability and/or transport of α6* nAChRs in dopaminergic neurons and influences their subunit composition. However, β3 subunit expression is not essential for the expression of α6*, high-affinity α-CtxMII binding nAChRs.