Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine

Fenster, Catherine P.; Rains, M. Felicia; Noerager, Brett; Quick, Michael W.; Lester, Robin A. J.

doi:10.1523/jneurosci.17-15-05747.1997

Cited by 332Nicotinic Acetylcholine Receptors StudyReceptor Mechanisms and SignalingNeuroscience and Neuropharmacology Research

Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine

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Fenster, Catherine P., Rains, M. Felicia, Noerager, Brett, Quick, Michael W., Lester, Robin A. J.·1997·The Journal of Neuroscience

DOI 10.1523/jneurosci.17-15-05747.1997PMC PMC6573211

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Abstract

The influence of alpha and beta subunits on the properties of nicotine-induced activation and desensitization of neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes was examined. Receptors containing alpha4 subunits were more sensitive to activation by nicotine than alpha3-containing receptors. At low concentrations of nicotine, nAChRs containing beta2 subunits reached near-maximal desensitization more rapidly than beta4-containing receptors. The concentration of nicotine producing half-maximal desensitization was influenced by the particular alpha subunit expressed; similar to results for activation, alpha4-containing receptors were more sensitive to desensitizing levels of nicotine than alpha3-containing receptors. The alpha subunit also influenced the rate of recovery from desensitization; this rate was approximately inversely proportional to the apparent nicotine affinity for the desensitized state. The homomeric alpha7 receptor showed the lowest sensitivity to nicotine for both activation and desensitization; alpha7 nAChRs also demonstrated the fastest desensitization kinetics. These subunit-dependent properties remained in the presence of external calcium, although subtle, receptor subtype-specific effects on both the apparent affinities for activation and desensitization and the desensitization kinetics were noted. These data imply that the subunit composition of various nAChRs determines the degree to which receptors are desensitized and/or activated by tobacco-related levels of nicotine. The subtype-specific balance between receptor activation and desensitization should be considered important when the cellular and behavioral actions of nicotine are interpreted.

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Chronic nicotine exposure induces up-regulation of nAChRs and profound desensitization of these receptors in vitro.
“Chronic nicotine exposure induces up-regulation of nAChRs, but also profound desensitization of these receptors in vitro (Fenster et al., 1997; Grady et al., 1994).”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Fenster et al., 1997

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Authors: Fenster, C. P., Rains, M. F., Noerager, B., Quick, M. W., & Lester, R. A. J.
Affiliations: University of Alabama at Birmingham (US)
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1997-08-01
Volume: 17
Issue: 15
Pages: 5747-5759
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.17-15-05747.1997
PMC: PMC6573211
OpenAlex: W2098098632
Cited by: 332
References: 71
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 10 · 2022: 5 · 2021: 10 · 2020: 6 · 2019: 8 · 2018: 4 · 2017: 7 · 2016: 8 · 2015: 18 · 2014: 16 · 2013: 16 · 2012: 7
FWCI: 7.59
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: W. M. Keck Foundation
U.S. Public Health Service
National Cancer Institute (CA-13 148, P30CA013148)
National Institute of Neurological Disorders and Stroke (R29NS031669, R29 NS31669)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: nicotinic acetylcholine receptors, receptor desensitization, nicotine, subunit composition, alpha subunit, beta subunit, alpha4 subunit, alpha3 subunit, alpha7 subunit, receptor activation, recovery from desensitization, calcium, neuronal receptors
MeSH terms: Animals, Dose-Response Relationship, Drug, Nicotine, Oocytes, Receptors, Cholinergic, Xenopus

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Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine

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