ArticleProceedings of the National Academy of Sciences of the United States of America2013
Stoichiometry for drug potentiation of a pentameric ion channel.
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 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Novel interplay between agonist and calcium binding sites modulates drug potentiation of α7 acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2024Article
- Derepression may masquerade as activation in ligand-gated ion channels.Nature communications · 2023Article
- Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously.eLife · 2022Article
- A single historical substitution drives an increase in acetylcholine receptor complexity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The desensitization pathway of GABANature communications · 2020Article
- Potentiation of a neuronal nicotinic receptor via pseudo-agonist site.Cellular and molecular life sciences : CMLS · 2019Article
- Article
- A human-specific, truncated α7 nicotinic receptor subunit assembles with full-length α7 and forms functional receptors with different stoichiometries.The Journal of biological chemistry · 2018Article
- Molecular function of the novel α7β2 nicotinic receptor.Cellular and molecular life sciences : CMLS · 2018Article
- Nicotinic acetylcholine receptors at the single-channel level.British journal of pharmacology · 2018Review
- Orthosteric and allosteric potentiation of heteromeric neuronal nicotinic acetylcholine receptors.British journal of pharmacology · 2018Review
- The dual-gate model for pentameric ligand-gated ion channels activation and desensitization.The Journal of physiology · 2018Review
- Molecular function of α7 nicotinic receptors as drug targets.The Journal of physiology · 2018Review
- Stoichiometry for α-bungarotoxin block of α7 acetylcholine receptors.Nature communications · 2015Article
- Concatenated hERG1 tetramers reveal stoichiometry of altered channel gating by RPR-260243.Molecular pharmacology · 2015Article
- Stoichiometry of altered hERG1 channel gating by small molecule activators.The Journal of general physiology · 2014Article
- Stoichiometry for activation of neuronal α7 nicotinic receptors.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- The additional ACh binding site at the α4(+)/α4(-) interface of the (α4β2)2α4 nicotinic ACh receptor contributes to desensitization.British journal of pharmacology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Drug modulation of ion channels is a powerful means to alter physiological responses for therapeutic benefit, yet the structural bases of modulation remain poorly understood. Here we study potentiation of nicotinic α7 acetylcholine receptors, which are emerging drug targets in several neurological disorders. α7 receptors are ligand-gated ion channels composed of five identical subunits, each bearing a site for the potentiating drug PNU-120596 (PNU). How the individual subunits contribute to PNU potentiation is not known. Taking advantage of a PNU-resistant mutant, we generated receptors composed of normal and PNU-resistant subunits and tagged one of the subunits with conductance mutations to report subunit stoichiometry. We then used patch clamp recording to monitor PNU potentiation of single α7 receptors with defined stoichiometry in real time. We find that potentiation depends steeply on the number of PNU-resistant subunits and that four, and possibly five, subunits must be sensitive to PNU for potentiation to occur. Thus, by monitoring the activity of every possible subunit combination, our findings predict that at the macroscopic level, PNU potentiation is highly cooperative.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.