ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 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
104 citing papers in PubMed, 164 citations in OpenAlex.
- Hesperetin-7-Nutrients · 2023Trial
- Symmetry-driven gating of TRPM8 by PIPNature communications · 2026Article
- Up-Regulation of the TRPM8 Channel Attenuates TRPC1-Mediated Store-Operated Calcium Entry in Abdominal Aortic Aneurysm.Biomolecules · 2026Article
- HPLC Purification of TRPM8 and Experimental Confirmation of Its Cholesterol Affinity on Synthetic Lipid Raft-like Models.Life (Basel, Switzerland) · 2026Article
- Thermosensitivity of TREK K2P channels is controlled by a PKA switch and depends on the microtubular network.Pflugers Archiv : European journal of physiology · 2025Article
- The structural basis of the G protein-coupled receptor and ion channel axis.Current research in structural biology · 2025Review
- Article
- Activation of central and peripheral transient receptor potential melastatin 8 increases susceptibility to spreading depolarization and facilitates trigeminal neuroinflammation.The journal of headache and pain · 2025Article
- Protein dynamics underlies strong temperature dependence of heat receptors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons.Neurology. Genetics · 2024Article
- TRPM3, TRPM4, and TRPM5 as thermo-sensitive channels.The journal of physiological sciences : JPS · 2024Review
- Temperature-Dependent Activation of Thermosensitive Transient Receptor Potential Channels.Advances in experimental medicine and biology · 2024Review
- TMEM120A/TACAN: A putative regulator of ion channels, mechanosensation, and lipid metabolism.Channels (Austin, Tex.) · 2023Review
- A suicidal mechanism for the exquisite temperature sensitivity of TRPV1.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Targeting Nociceptive Neurons and Transient Receptor Potential Channels for the Treatment of Migraine.International journal of molecular sciences · 2023Review
- Molecular determinants of TRPM8 function: key clues for a cool modulation.Frontiers in pharmacology · 2023Review
- Carbon dioxide treatment modulates phosphatidic acid signaling and stress response to improve chilling tolerance and postharvest quality in paprika.Frontiers in plant science · 2023Article
- Therapeutic potential of TRPM8 channels in cancer treatment.Frontiers in pharmacology · 2023Review
- A journey from molecule to physiology andFrontiers in pharmacology · 2023Review
- The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain.Nature communications · 2022Article
44 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
The transient receptor potential melastatin 8 (TRPM8) ion channel is a major sensor of environmental cold temperatures. It is activated by cold and chemical agonists, such as menthol and icilin. The activation of these channels both by cold and cooling agents requires the presence of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)]. The mechanism of TRPM8 activation by physical and chemical factors is unknown, and the involvement of cellular signaling pathways has been considered. Here we have characterized the gating mechanism of the rat TRPM8 reconstituted in planar lipid bilayers and its activation by different stimuli. In this system, the influence of cellular signaling pathways can be excluded. We found that TRPM8 activated by cold exhibits steep temperature dependence [temperature coefficient (Q(10)) of ∼40], and the channel openings are accompanied by large changes in entropy and enthalpy, suggesting a substantial conformation change. TRPM8 channel behavior upon menthol and icilin activation was distinguishable, and the effect of icilin depended on the presence of calcium on the intracellular side of the protein. Here we also demonstrate that PI(4,5)P(2) is the prime factor that impacts the gating of TRPM8 and that other phosphoinositides are less efficient in supporting channel activity. Menthol increases the potency of PI(4,5)P(2) to activate the channels and increases binding of phosphoinositides to the full-length channel protein. Our data demonstrate conclusively that TRPM8 is gated by cold and its chemical agonists directly, and that dependence of its gating on PI(4,5)P(2) is a result of direct specific interactions with the lipid.
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.