ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Uncoupling proton activation of vanilloid receptor TRPV1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- The role of acid-sensitive ion channels in panic disorder: a systematic review of animal studies and meta-analysis of human studies.Translational psychiatry · 2018Pooled it
- Thermoring basis for the proton-driven heat activation of a cation-selective channel in myriapods.Scientific reports · 2025Article
- Neurotoxins Acting on TRPV1-Building a Molecular Template for the Study of Pain and Thermal Dysfunctions.Toxins · 2025Review
- Functional and structural insights into activation of TRPV2 by weak acids.The EMBO journal · 2024Article
- A human TRPV1 genetic variant within the channel gating domain regulates pain sensitivity in rodents.The Journal of clinical investigation · 2023Article
- A molecular perspective on identifying TRPV1 thermosensitive regions and disentangling polymodal activation.Temperature (Austin, Tex.) · 2023Review
- CaInternational journal of molecular sciences · 2022Review
- Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.Nature communications · 2022Article
- Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development.International journal of molecular sciences · 2022Review
- Article
- Heat-dependent opening of TRPV1 in the presence of capsaicin.Nature structural & molecular biology · 2021Article
- Mechanisms of proton inhibition and sensitization of the cation channel TRPV3.The Journal of general physiology · 2021Article
- Properties and Differential Expression of HFrontiers in physiology · 2021Review
- Vitamin D is an endogenous partial agonist of the transient receptor potential vanilloid 1 channel.The Journal of physiology · 2020Article
- Evidence that the TRPV1 S1-S4 membrane domain contributes to thermosensing.Nature communications · 2020Article
- Structural mechanisms of transient receptor potential ion channels.The Journal of general physiology · 2020Review
- Structure determination of the human TRPV1 ankyrin-repeat domain under nonreducing conditions.Acta crystallographica. Section F, Structural biology communications · 2020Article
- The Mysteries of Capsaicin-Sensitive Afferents.Frontiers in physiology · 2020Review
- Article
- Neuronal transient receptor potential (TRP) channels and noxious sensory detection in sickle cell disease.Neuroscience letters · 2019Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Multimodal gating is an essential feature of many TRP ion channels, enabling them to respond to complex cellular environments. TRPV1, a pain receptor involved in nociception at the peripheral nerve terminals, can be activated by a range of physical and chemical stimuli (e.g., capsaicin, proton, and heat) and further sensitized by proinflammatory substances. How a single receptor achieves this multiplicity of functionality is poorly understood at the molecular level. Here, we investigated the structural basis of proton activation of TRPV1. Chimeric channels between rTRPV1 and the low pH-insensitive homolog TRPV2 were constructed by systematically exchanging the extracellular domains and were characterized using whole-cell recording in transiently transfected HEK293 cells. Two discrete domains, one involving the pore helix and the other the S3-S4 linker, were found crucial for direct activation of the channel by low pH. Single residue mutations in either domain (T633A/V538L) abrogated the proton-evoked current while preserving the capsaicin and heat responses and their potentiation by mildly acidic pH. Both residues exert a gating effect through hydrophobic interactions. Our results unravel novel information on the structural basis of channel function, and support the existence of discrete domains for multimodal gating of the channel. In view of the resemblance of the pore of TRPV1 to KcsA, our findings also provide evidence on the pore helix as an active component in channel gating in addition to its role in ion permeation.
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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.