ArticleProceedings of the National Academy of Sciences of the United States of America2013
Asymmetric transmitter binding sites of fetal muscle acetylcholine receptors shape their synaptic response.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Article
- A single molecular distance predicts agonist binding energy in nicotinic receptors.The Journal of general physiology · 2019Article
- Cyclic activation of endplate acetylcholine receptors.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A mechanism for acetylcholine receptor gating based on structure, coupling, phi, and flip.The Journal of general physiology · 2017Article
- Structural correlates of affinity in fetal versus adult endplate nicotinic receptors.Nature communications · 2016Article
- Activation of endplate nicotinic acetylcholine receptors by agonists.Biochemical pharmacology · 2015Review
- Positive and Negative Allosteric Modulation of an α1β3γ2 γ-Aminobutyric Acid Type A (GABAA) Receptor by Binding to a Site in the Transmembrane Domain at the γ+-β- Interface.The Journal of biological chemistry · 2015Article
- Agonist activation of a nicotinic acetylcholine receptor.Neuropharmacology · 2015Review
- Functional differences between neurotransmitter binding sites of muscle acetylcholine receptors.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Catch-and-hold activation of muscle acetylcholine receptors having transmitter binding site mutations.Biophysical journal · 2014Article
- Agonists binding nicotinic receptors elicit specific channel-opening patterns at αγ and αδ sites.The Journal of physiology · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
Neuromuscular acetylcholine receptors (AChRs) have two transmitter binding sites: at α-δ and either α-γ (fetal) or α-ε (adult) subunit interfaces. The γ-subunit of fetal AChRs is indispensable for the proper development of neuromuscular synapses. We estimated parameters for acetylcholine (ACh) binding and gating from single channel currents of fetal mouse AChRs expressed in tissue-cultured cells. The unliganded gating equilibrium constant is smaller and less voltage-dependent than in adult AChRs. However, the α-γ binding site has a higher affinity for ACh and provides more binding energy for gating compared with α-ε; therefore, the diliganded gating equilibrium constant at -100 mV is comparable for both receptor subtypes. The -2.2 kcal/mol extra binding energy from α-γ compared with α-δ and α-ε is accompanied by a higher resting affinity for ACh, mainly because of slower transmitter dissociation. End plate current simulations suggest that the higher affinity and increased energy from α-γ are essential for generating synaptic responses at low pulse [ACh].
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Registered trials
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