ArticleeLife2016
An external sodium ion binding site controls allosteric gating in TRPV1 channels.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 72 citations in OpenAlex.
- Comparing cryo-EM methods and molecular dynamics simulation to investigate heterogeneity in ligand-bound TRPV1.Nature communications · 2025Article
- Pathway-dependent cold activation of heat-responsive TRPV channels.Scientific reports · 2025Article
- Article
- Conservation of the cooling agent binding pocket within the TRPM subfamily.bioRxiv : the preprint server for biology · 2024Article
- Article
- Mechanisms of sensory adaptation and inhibition of the cold and menthol receptor TRPM8.Science advances · 2024Article
- Genetic code expansion, click chemistry, and light-activated PI3K reveal details of membrane protein trafficking downstream of receptor tyrosine kinases.bioRxiv : the preprint server for biology · 2024Article
- Dilation of ion selectivity filters in cation channels.Trends in biochemical sciences · 2024Review
- Permeant cations modulate pore dynamics and gating of TRPV1 ion channels.The Journal of general physiology · 2024Article
- Implications of a temperature-dependent heat capacity for temperature-gated ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Cannabidiol sensitizes TRPV2 channels to activation by 2-APB.bioRxiv : the preprint server for biology · 2023Article
- Mutagenesis studies of TRPV1 subunit interfaces informed by genomic variant analysis.Biophysical journal · 2023Article
- A molecular perspective on identifying TRPV1 thermosensitive regions and disentangling polymodal activation.Temperature (Austin, Tex.) · 2023Review
- Dual amplification strategy turns TRPM2 channels into supersensitive central heat detectors.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Genetically-encoded BRET probes shed light on ligand bias-induced variable ion selectivity in TRPV1 and P2X5/7.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation.International journal of molecular sciences · 2022Article
- Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.Nature communications · 2022Article
- Heat-dependent opening of TRPV1 in the presence of capsaicin.Nature structural & molecular biology · 2021Article
- Mapping temperature-dependent conformational change in the voltage-sensing domain of an engineered heat-activated KProceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
TRPV1 channels in sensory neurons are integrators of painful stimuli and heat, yet how they integrate diverse stimuli and sense temperature remains elusive. Here, we show that external sodium ions stabilize the TRPV1 channel in a closed state, such that removing the external ion leads to channel activation. In studying the underlying mechanism, we find that the temperature sensors in TRPV1 activate in two steps to favor opening, and that the binding of sodium to an extracellular site exerts allosteric control over temperature-sensor activation and opening of the pore. The binding of a tarantula toxin to the external pore also exerts control over temperature-sensor activation, whereas binding of vanilloids influences temperature-sensitivity by largely affecting the open/closed equilibrium. Our results reveal a fundamental role of the external pore in the allosteric control of TRPV1 channel gating and provide essential constraints for understanding how these channels can be tuned by diverse stimuli.
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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.