Both alpha- and beta-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors
Open accessAbstract
A family of genes has been identified that encodes subunits of nicotinic acetylcholine receptors (nAChRs) and is expressed in the nervous system. Functional neuronal nAChRs can be expressed in Xenopus oocytes by injection of RNA encoding 1 of 2 different beta-subunits (beta 2, beta 4) in pairwise combination with RNA encoding 1 of 3 different alpha-subunits (alpha 2, alpha 3, alpha 4). We examined the sensitivity of these 6 different alpha- beta-subunit combinations to the nicotinic agonists ACh, nicotine, cytisine, and 1,1-dimethyl-4-phenylpiperazinium (DMPP). Each subunit combination displayed a distinct pattern of sensitivity to these 4 agonists. The alpha 2 beta 2 combination was 5-fold more sensitive to nicotine than to acetylcholine, while the alpha 3 beta 2 combination was 17-fold less sensitive to nicotine than to ACh, and the alpha 3 beta 4 combination was equally sensitive to both nicotine and ACh. nAChRs composed of alpha 2, alpha 3, or alpha 4 in combination with beta 2 were 14-100-fold less sensitive to cytisine than to ACh. In contrast, nAChRs composed of alpha 2, alpha 3, or alpha 4 in combination with beta 4 were 3-17-fold more sensitive to cytisine than to ACh. The alpha 2 beta 2, alpha 3 beta 2, and alpha 3 beta 4 combinations were each equally sensitive to DMPP and ACh, while the alpha 2 beta 4, alpha 4 beta 2, and alpha 4 beta 4 combinations were 4-24-fold less sensitive to DMPP than to ACh. We also demonstrated that these differences are neither a consequence of variation in the relative amounts of RNA injected nor an artifact of oocyte expression. The oocyte system can accurately express ligand-gated ion channels because mouse muscle nAChRs expressed in oocytes display pharmacological properties similar to those reported for these receptors expressed on BC3H-1 cells. We conclude that both the alpha- and the beta-subunits contribute to the pharmacological characteristics of neuronal nAChRs.
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- Authors
- Luetje, C., & Patrick, J.
- Affiliations
- Baylor College of Medicine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1991-03-01
- Volume
- 11
- Issue
- 3
- Pages
- 837-845
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6575344
- OpenAlex
- W1799536240
- Cited by
- 558
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 7 · 2022: 4 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 3 · 2015: 15 · 2014: 9 · 2013: 5 · 2012: 10
- FWCI
- 10.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Muscular Dystrophy Association
- National Institutes of Health (5f32mh009749-02)
- National Institute of Mental Health (1 F32 MH09749)
- National Institute of Neurological Disorders and Stroke (R01NS013546, 2 RO1 NS13546)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- neuronal nicotinic acetylcholine receptors, alpha subunit, beta subunit, agonist sensitivity, nicotine, acetylcholine, cytisine, DMPP, ligand-gated ion channels, receptor subunit composition, oocyte expression system
- MeSH terms
- Quinolizidine Alkaloids, Acetylcholine, Alkaloids, Animals, Azocines, Dimethylphenylpiperazinium Iodide, Female, Kinetics, Membrane Potentials, Microinjections, Neurons, Nicotine, Oocytes, Quinolizines, Receptors, Nicotinic, RNA, Transcription, Genetic, Xenopus laevis, Macromolecular Substances, In Vitro Techniques
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