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Vol. 63, Issue 2, 332-341, February 2003
4
2 Nicotinic Acetylcholine
Receptors
Department of Neuroscience, University of Pennsylvania Medical
School, Philadelphia, Pennsylvania
Two functional types of nicotinic acetylcholine receptors
(nAChRs) are expressed when human embryonic kidney cells are
permanently transfected with equal amounts of human 
4 and 
2
subunit cDNAs. Most (82%) of these nAChRs exhibit an EC50
of 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 4 and 2 mRNAs in
Xenopus 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 2
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 (4)3(2)2.
Overnight treatment with nicotine increased the number of nAChRs and
increased the proportion of the (4)2(2)3
stoichiometry. Alternate 42 nAChR stoichiometries with distinct
functional properties raise the possibility for an interesting mode of
synaptic regulation for nicotinic signaling in the mammalian brain.
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