PT  - JOURNAL ARTICLE
AU  - Mark E. Nelson
AU  - Alexander Kuryatov
AU  - Catherine H. Choi
AU  - Yan Zhou
AU  - Jon Lindstrom
TI  - Alternate Stoichiometries of α4β2 Nicotinic Acetylcholine Receptors
AID  - 10.1124/mol.63.2.332
DP  - 2003 Feb 01
TA  - Molecular Pharmacology
PG  - 332--341
VI  - 63
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/63/2/332.short
4100  - http://molpharm.aspetjournals.org/content/63/2/332.full
SO  - Mol Pharmacol2003 Feb 01; 63
AB  - Two functional types of nicotinic acetylcholine receptors (nAChRs) are expressed when human embryonic kidney cells are permanently transfected with equal amounts of human α4 and β2 subunit cDNAs. Most (82%) of these nAChRs exhibit an EC50of 74 ± 6 μM for ACh, a much lower sensitivity than the remaining fraction (EC50 of 0.7 ± 0.4 μM) or than expected from expression of equal amounts of α4 and β2 mRNAs inXenopus laevis oocytes. We have found three conditions that can increase the number of nAChRs with high sensitivity to activation. These are: 1) transient transfection with additional β2 subunits, 2) overnight incubation in nicotine, or 3) overnight culture at 29°C. Using metabolic labeling with [35S]methionine to measure subunit stoichiometry, we found that the majority of nAChRs had a stoichiometry of (α4)3(β2)2. Overnight treatment with nicotine increased the number of nAChRs and increased the proportion of the (α4)2(β2)3stoichiometry. Alternate α4β2 nAChR stoichiometries with distinct functional properties raise the possibility for an interesting mode of synaptic regulation for nicotinic signaling in the mammalian brain. The American Society for Pharmacology and Experimental Therapeutics