ArticleThe Journal of biological chemistry2014
Temperature and voltage coupling to channel opening in transient receptor potential melastatin 8 (TRPM8).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Conformational Fingerprints Underlying Thermal Modulation of PAC/TMEM206 Gating.International journal of molecular sciences · 2026Article
- Tuning the gate and the gear: The LRRC26 (γ1) subunit modulates intrinsic gating and voltage-sensor coupling of the BK channel.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The BK channel-NS1619 agonist complex reveals molecular insights into allosteric activation gating.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Quantifying activation delay and the Cole-More shift via current derivatives.Biophysical journal · 2026Article
- Energy landscape of a Kv channel revealed by temperature steps while perturbing its electromechanical coupling.Nature communications · 2025Article
- Borneol's Pre-Clinical Analgesic Efficacy: Mediated by Receptor and Immune Mechanisms.Journal of pain research · 2025Review
- Ion channels of cold transduction and transmission.The Journal of general physiology · 2024Review
- Evidence that the cold- and menthol-sensing functions of the human TRPM8 channel evolved separately.Science advances · 2024Article
- Site-Specific Transient Receptor Potential Channel Mechanisms and Their Characteristics for Targeted Chronic Itch Treatment.Biomolecules · 2024Review
- Ion channel thermodynamics studied with temperature jumps measured at the cell membrane.Biophysical journal · 2023Article
- Regulation of ThermoTRP Channels by PIP2 and Cholesterol.Advances in experimental medicine and biology · 2023Article
- A journey from molecule to physiology andFrontiers in pharmacology · 2023Review
- 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
- On the modulation of TRPM channels: Current perspectives and anticancer therapeutic implications.Frontiers in oncology · 2022Review
- The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances.Frontiers in molecular neuroscience · 2022Review
- L-Menthol-Loadable Electrospun Fibers of PMVEMA Anhydride for Topical Administration.Pharmaceutics · 2021Article
- TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.International journal of molecular sciences · 2021Review
- Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain.International journal of molecular sciences · 2021Article
- TRPM8 Channel Promotes the Osteogenic Differentiation in Human Bone Marrow Mesenchymal Stem Cells.Frontiers in cell and developmental biology · 2021Article
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5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expressed in somatosensory neurons of the dorsal root and trigeminal ganglion, the transient receptor potential melastatin 8 (TRPM8) channel is a Ca(2+)-permeable cation channel activated by cold, voltage, phosphatidylinositol 4,5-bisphosphate, and menthol. Although TRPM8 channel gating has been characterized at the single channel and macroscopic current levels, there is currently no consensus regarding the extent to which temperature and voltage sensors couple to the conduction gate. In this study, we extended the range of voltages where TRPM8-induced ionic currents were measured and made careful measurements of the maximum open probability the channel can attain at different temperatures by means of fluctuation analysis. The first direct measurements of TRPM8 channel temperature-driven conformational rearrangements provided here suggest that temperature alone is able to open the channel and that the opening reaction is voltage-independent. Voltage is a partial activator of TRPM8 channels, because absolute open probability values measured with fully activated voltage sensors are less than 1, and they decrease as temperature rises. By unveiling the fast temperature-dependent deactivation process, we show that TRPM8 channel deactivation is well described by a double exponential time course. The fast and slow deactivation processes are temperature-dependent with enthalpy changes of 27.2 and 30.8 kcal mol(-1). The overall Q10 for the closing reaction is about 33. A three-tiered allosteric model containing four voltage sensors and four temperature sensors can account for the complex deactivation kinetics and coupling between voltage and temperature sensor activation and channel opening.
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