ArticleProceedings of the National Academy of Sciences of the United States of America2004
Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers.
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181 citing papers in PubMed.
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- Pathway-dependent cold activation of heat-responsive TRPV channels.Scientific reports · 2025Article
- Rational tuning of temperature sensitivity of the TRPM8 channel.EMBO reports · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- A dedicated skin-to-brain circuit for cool sensation in mice.Nature communications · 2025Article
- HCN4 channels sense temperature and determine heart rate responses to heat.Nature communications · 2025Article
- Thermo-TRP regulation by endogenous factors and its physiological function at core body temperature.Physiological reports · 2025Review
- Ion channels of cold transduction and transmission.The Journal of general physiology · 2024Review
- TRPM3, TRPM4, and TRPM5 as thermo-sensitive channels.The journal of physiological sciences : JPS · 2024Review
- Evidence that the cold- and menthol-sensing functions of the human TRPM8 channel evolved separately.Science advances · 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
- Article
- Temperature gating in thermoTRPs may depend on temperature-dependent heat capacity differences.Temperature (Austin, Tex.) · 2024Article
- The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024Review
- Temperature-Dependent Activation of Thermosensitive Transient Receptor Potential Channels.Advances in experimental medicine and biology · 2024Review
- Extracting thermodynamic properties from van 't Hoff plots with emphasis on temperature-sensing ion channels.Temperature (Austin, Tex.) · 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
- 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
121 more citing papers are in PubMed but not listed here.
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The cold and menthol receptor, TRPM8, also designated CMR1, is a member of the transient receptor potential (TRP) family of excitatory ion channels. TRPM8 is a channel activated by cold temperatures, voltage, and menthol. In this study, we characterize the cold- and voltage-induced activation of TRPM8 channel in an attempt to identify the temperature- and voltage-dependent components involved in channel activation. Under equilibrium conditions, decreasing temperature has two effects. (i) It shifts the normalized conductance vs. voltage curves toward the left, along the voltage axis. This effect indicates that the degree of order is higher when the channel is in the open configuration. (ii) It increases the maximum channel open probability, suggesting that temperature affects both voltage-dependent and -independent pathways. In the temperature range between 18 degrees C and 25 degrees C, large changes in enthalpy (DeltaH=-112 kcal/mol) and entropy (DeltaS=-384 cal/mol K) accompany the activation process. The Q10 calculated in the same temperature range is 24. This thermodynamic analysis strongly suggests that the process of opening involves large conformational changes of the channel-forming protein. Therefore, the highly temperature-dependent transition between open and closed configurations is possible because enthalpy and entropy are both large and compensate each other. Our data also demonstrate that temperature and voltage interact allosterically to enhance channel opening.
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