Rapid kinetics of agonist binding and permeability response analyzed in parallel on acetylcholine receptor rich membranes from Torpedo marmorata
Open accessAbstract
Excitable acetylcholine receptor rich membrane fragments from Torpedo marmorata have been used to measure, in parallel, (1) the permeability response to the fluorescent cholinergic agonist Dns-C6-Cho (in the 0.1 microM to millimolar concentration range) characterized by both the initial rate of Li+ transport and the rate of channel closure using the rapid-mixing quench-flow technique and (2) the kinetics of interaction of Dns-C6-Cho with the acetylcholine receptor sites using the rapid-mixing stopped-flow technique. Analysis of the kinetics of Dns-C6-Cho binding in the millisecond to minute time scale leads to the identification of at least three conformational states of the acetylcholine receptor: a "low-affinity" one (approximately 50 microM) that can be interconverted in the fraction of a second to a transient state of "intermediate affinity" (approximately 1 microM), followed by the final stabilization, in the second to minute time range, of a state of "high affinity" (approximately 3 nM). Comparison of Dns-C6-Cho binding data with the permeability response to the same agonist demonstrates that the binding to the low-affinity conformation(s) of the acetylcholine receptor sites coincides with the triggering of the permeability increase--or "activation"--and the transitions to the intermediate- and high-affinity states with the two-step process of channel closing--or "desensitization". The data are interpreted in terms of a minimum four-state "allosteric" model for the acet…
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Desensitized nAChRs have a higher affinity for ACh and other ligands than those in the activatable state.
“Despite the decreased response of AChRs to agonists in the desensitized state, desensitized nAChRs have a higher affinity for ACh and other ligands than those in the “activatable” state (Heidmann et al., 1983; Quick and Lester, 2002);”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Heidmann et al., 1983
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PICCIOTTO, M., ADDY, N., MINEUR, Y., & BRUNZELL, D. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.12.005 · Cited by 451 · see citing works
- Authors
- Heidmann, T., Bernhardt, J., Neumann, E., & Changeux, J. P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1983-11-08
- Volume
- 22
- Issue
- 23
- Pages
- 5452-5459
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2043557877
- Cited by
- 110
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2021: 2 · 2019: 1 · 2018: 1 · 2014: 5 · 2013: 3 · 2012: 2
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- green
- pub.uni-bielefeld.de
- Licence
- other-oa
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PUB – Publications at Bielefeld University (Bielefeld University) (submittedVersion, other-oa)
- Publikationen an der Universität Bielefeld (Universität Bielefeld) (submittedVersion, other-oa)
- Funders
- Muscular Dystrophy Association
- Deutsche Forschungsgemeinschaft
- Institut National de la Santé et de la Recherche Médicale
- Fondation de France
- Centre National de la Recherche Scientifique
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- acetylcholine receptor, Torpedo marmorata, ion channel permeability, channel desensitization, channel closure, receptor conformational states, allosteric model, four-state model, low-affinity binding, high-affinity state, stopped flow
- MeSH terms
- Quaternary Ammonium Compounds, Animals, Cell Membrane Permeability, Dansyl Compounds, Kinetics, Mathematics, Receptors, Cholinergic, Torpedo
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