ArticleBritish journal of pharmacology2013
The additional ACh binding site at the α4(+)/α4(-) interface of the (α4β2)2α4 nicotinic ACh receptor contributes to desensitization.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- A potential cost of evolving epibatidine resistance in poison frogs.BMC biology · 2023Article
- Structural Insights into the Role of β3 nAChR Subunit in the Activation of Nicotinic Receptors.Molecules (Basel, Switzerland) · 2022Article
- The α9α10 nicotinic acetylcholine receptor: a compelling drug target for hearing loss?Expert opinion on therapeutic targets · 2022Review
- Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling.Archives of toxicology · 2021Article
- Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons.Archives of toxicology · 2021Article
- Concatemers to re-investigate the role of α5 in α4β2 nicotinic receptors.Cellular and molecular life sciences : CMLS · 2021Article
- The Hair Cell α9α10 Nicotinic Acetylcholine Receptor: Odd Cousin in an Old Family.Frontiers in cellular neuroscience · 2021Review
- Potentiation of a neuronal nicotinic receptor via pseudo-agonist site.Cellular and molecular life sciences : CMLS · 2019Article
- Molecular function of the novel α7β2 nicotinic receptor.Cellular and molecular life sciences : CMLS · 2018Article
- Orthosteric and allosteric potentiation of heteromeric neuronal nicotinic acetylcholine receptors.British journal of pharmacology · 2018Review
- The fifth subunit of the (α4β2)British journal of pharmacology · 2018Article
- Loops D, E and G in the Drosophila Dα1 subunit contribute to high neonicotinoid sensitivity of Dα1-chicken β2 nicotinic acetylcholine receptor.British journal of pharmacology · 2018Article
- Stoichiometry of the Heteromeric Nicotinic Receptors of the Renshaw Cell.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors.Current neuropharmacology · 2018Review
- The (Molecular pharmacology · 2017Article
- α4β2 Nicotinic Acetylcholine Receptors: RELATIONSHIPS BETWEEN SUBUNIT STOICHIOMETRY AND FUNCTION AT THE SINGLE CHANNEL LEVEL.The Journal of biological chemistry · 2017Article
- Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound α2 homopentamer.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- A Novel α2/α4 Subtype-selective Positive Allosteric Modulator of Nicotinic Acetylcholine Receptors Acting from the C-tail of an α Subunit.The Journal of biological chemistry · 2015Article
- High affinity and low affinity heteromeric nicotinic acetylcholine receptors at central synapses.The Journal of physiology · 2014Review
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4 authors.
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Abstract
background and purposeNicotinic ACh (α4β2)2α4 receptors are highly prone to desensitization by prolonged exposure to low concentrations of agonist. Here, we report on the sensitivity of the three agonist sites of the (α4β2)2α4 to desensitization induced by prolonged exposure to ACh. We present electrophysiological data that show that the agonist sites of the (α4β2)2α4 receptor have different sensitivity to desensitization and that full receptor occupation decreases sensitivity to desensitization. EXPERIMENTAL APPROACH: Two-electrode voltage-clamp electrophysiology was used to study the desensitization of concatenated (α4β2)2α4 receptors expressed heterologously in Xenopus oocytes. Desensitization was assessed by measuring the degree of functional inhibition caused by prolonged exposure to ACh, as measured under equilibrium conditions. We used the single-point mutation α4W182A to measure the contribution of individual agonist sites to desensitization. KEY
results(α4β2)2α4 receptors are less sensitive to activation and desensitization by ACh than (α4β2)2β2 receptors. Incorporation of α4W182A into any of the agonist sites of concatenated (α4β2)2α4 receptors decreased sensitivity to activation and desensitization but the effects were more pronounced when the mutation was introduced into the α4(+)/α4(-) interface. CONCLUSIONS AND IMPLICATIONS: The findings suggest that the agonist sites in (α4β2)2α4 receptors are not functionally equivalent. The agonist site at the α4(+)/α4(-) interface defines the sensitivity of (α4β2)2α4 receptors to agonist-induced activation and desensitization. Functional differences between (α4β2)2α4 and (α4β2)2β2 receptors might shape the physiological and behavioural responses to nicotinic ligands when the receptors are exposed to nicotinic ligands for prolonged periods of times.
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