ArticleThe Journal of general physiology2012
Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations.
Article in The Journal of general physiology, 2012. 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.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Analysing an allelic series of rare missense variants of CACNA1I in a Swedish schizophrenia cohort.Brain : a journal of neurology · 2022Pooled it
- Distinct functional open states of the polymodal nociceptor TRPV1.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- An Extracellular Pore‑Targeting Peptide Defines a Designable Allosteric Site in TRPV2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fever-like temperatures improve cognitive deficits in the Scn2a autism mouse model via increases in potassium channel activity.Molecular psychiatry · 2026Article
- Thermoring basis for the proton-driven heat activation of a cation-selective channel in myriapods.Scientific reports · 2025Article
- Thermosensitivity of TREK K2P channels is controlled by a PKA switch and depends on the microtubular network.Pflugers Archiv : European journal of physiology · 2025Article
- Dual Role of TRPV1 Channels in Cerebral Stroke: An Exploration from a Mechanistic and Therapeutic Perspective.Molecular neurobiology · 2024Review
- Fluorescence labeling strategies for cell surface expression of TRPV1.The Journal of general physiology · 2024Article
- Fluorescence labeling strategies for the study of ion channel and receptor cell surface expression: A comprehensive toolkit for extracellular labeling of TRPV1.bioRxiv : the preprint server for biology · 2024Article
- KCNQ1 is an essential mediator of the sex-dependent perception of moderate cold temperatures.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Temperature-Dependent Activation of Thermosensitive Transient Receptor Potential Channels.Advances in experimental medicine and biology · 2024Review
- Non-canonical helical transitions and conformational switching are associated with characteristic flexibility and disorder indices in TRP and Kv channels.Channels (Austin, Tex.) · 2023Article
- Two single-point mutations in Ankyrin Repeat one drastically change the threshold temperature of TRPV1.Nature communications · 2023Article
- A molecular perspective on identifying TRPV1 thermosensitive regions and disentangling polymodal activation.Temperature (Austin, Tex.) · 2023Review
- Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms.Frontiers in molecular neuroscience · 2023Review
- Progress in the Structural Basis of thermoTRP Channel Polymodal Gating.International journal of molecular sciences · 2023Review
- 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
- Evolution of Transient Receptor Potential (TRP) Ion Channels in Antarctic Fishes (Cryonotothenioidea) and Identification of Putative Thermosensors.Genome biology and evolution · 2022Article
- De Novo Design of Peptidic Positive Allosteric Modulators Targeting TRPV1 with Analgesic Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
16 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate.
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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.