ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2020
An Unorthodox Mechanism Underlying Voltage Sensitivity of TRPV1 Ion Channel.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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
21 citing papers in PubMed, 31 citations in OpenAlex.
- An update on regulation of the polymodal TRPV4 channel by protein phosphorylation.Channels (Austin, Tex.) · 2026Review
- TRPV1 from the TRP family: Structure, function, implication in autoimmune diseases and potential therapies.Channels (Austin, Tex.) · 2026Review
- Review
- CGRP at the Neuroimmune Interface: Regulator of Host Defense, Tumor Immunity, and Tissue Homeostasis.Research (Washington, D.C.) · 2026Review
- The TRP channels serving as chemical-to-electrical signal converter.Physiological reviews · 2025Review
- Molecular basis of TRPV3 channel blockade by intracellular polyamines.Communications biology · 2025Article
- Functional determinants of lysophospholipid- and voltage-dependent regulation of TRPC5 channel.Cellular and molecular life sciences : CMLS · 2024Article
- Permeant cations modulate pore dynamics and gating of TRPV1 ion channels.The Journal of general physiology · 2024Article
- Terpenes inInternational journal of molecular sciences · 2023Article
- A new polymodal gating model of the proton-activated chloride channel.PLoS biology · 2023Article
- Blockade of TRPV channels by intracellular spermine.The Journal of general physiology · 2023Article
- Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia.Nature communications · 2023Article
- A molecular perspective on identifying TRPV1 thermosensitive regions and disentangling polymodal activation.Temperature (Austin, Tex.) · 2023Review
- Article
- 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
- Lipid-dependent sequential allosteric activation of heat-sensing TRPV1 channels by anchor-stereoselective "hot" vanilloid compounds and analogs.Biochemistry and biophysics reports · 2021Review
- Rational Design of a Modality-Specific Inhibitor of TRPM8 Channel against Oxaliplatin-Induced Cold Allodynia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Biomedical Implants with Charge-Transfer Monitoring and Regulating Abilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Article
- An Unorthodox Mechanism Underlying Voltage Sensitivity of TRPV1 Ion Channel.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
While the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1) channel is a polymodal nociceptor for heat, capsaicin, and protons, the channel's responses to each of these stimuli are profoundly regulated by membrane potential, damping or even prohibiting its response at negative voltages and amplifying its response at positive voltages. Therefore, voltage sensitivity of TRPV1 is anticipated to play an important role in shaping pain responses. How voltage regulates TRPV1 activation remains unknown. Here, it is shown that voltage sensitivity does not originate from the S4 segment like classic voltage-gated ion channels; instead, outer pore acidic residues directly partake in voltage-sensitive activation, with their negative charges collectively constituting the observed gating charges. Outer pore gating-charge movement is titratable by extracellular pH and is allosterically coupled to channel activation, likely by influencing the upper gate in the ion selectivity filter. Elucidating this unorthodox voltage-gating process provides a mechanistic foundation for understanding TRPV1 polymodal gating and opens the door to novel approaches regulating channel activity for pain management.
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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.