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Related Concept Videos

Thermosensation01:43

Thermosensation

Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR01:15

¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR

The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
¹H NMR of Conformationally Flexible Molecules: Temporal Resolution00:52

¹H NMR of Conformationally Flexible Molecules: Temporal Resolution

At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
Phase Transitions: Melting and Freezing02:39

Phase Transitions: Melting and Freezing

Heating a crystalline solid increases the average energy of its atoms, molecules, or ions, and the solid gets hotter. At some point, the added energy becomes large enough to partially overcome the forces holding the molecules or ions of the solid in their fixed positions, and the solid begins the process of transitioning to the liquid state or melting. At this point, the temperature of the solid stops rising, despite the continual input of heat, and it remains constant until all of the solid is...
Resting Membrane Potential01:24

Resting Membrane Potential

The relative difference in electrical charge, or voltage, between the inside and the outside of a cell membrane, is called the membrane potential. It is generated by differences in permeability of the membrane to various ions and the concentrations of these ions across the membrane.
The Inside of a Neuron is More Negative
The membrane potential of a cell can be measured by inserting a microelectrode into a cell and comparing the charge to a reference electrode in the extracellular fluid. The...
Thermal Sigmatropic Reactions: Overview01:16

Thermal Sigmatropic Reactions: Overview

Sigmatropic rearrangements are a class of pericyclic reactions in which a σ bond migrates from one part of a π system to another. These are intramolecular rearrangements where the total number of σ and π bonds remain unchanged.
Sigmatropic shifts are classified based on an order term [i, j ], where i and j indicate the number of atoms across which each end of the σ bond migrates. Below are examples of a [3,3] sigmatropic shift in 1,5-hexadiene, referred to as...

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Related Experiment Video

Updated: Jul 3, 2026

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
08:35

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice

Published on: March 17, 2015

Temperature-Dependent Menthol Binding across TRPM8 Conformational States.

Leonardo Cirqueira1, Guilherme Lucas2, Carmen Domene1

  • 1Department of Chemistry, University of Bath, Bath BA2 7AX, United Kingdom.

Journal of the American Chemical Society
|July 1, 2026
PubMed
Summary

Temperature affects how menthol binds to the TRPM8 channel by altering its distribution. This explains menthol

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Purification and Reconstitution of TRPV1 for Spectroscopic Analysis
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Purification and Reconstitution of TRPV1 for Spectroscopic Analysis

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Related Experiment Videos

Last Updated: Jul 3, 2026

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
08:35

A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice

Published on: March 17, 2015

Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
12:09

Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4

Published on: December 31, 2013

Purification and Reconstitution of TRPV1 for Spectroscopic Analysis
11:53

Purification and Reconstitution of TRPV1 for Spectroscopic Analysis

Published on: July 3, 2018

Area of Science:

  • Molecular biology
  • Biophysics
  • Computational chemistry

Background:

  • TRPM8 (transient receptor potential melastatin 8) mediates cold sensation and is activated by menthol.
  • The precise mechanism of menthol activation and temperature's influence on ligand binding remain unclear.
  • Polymodal ion channels exhibit complex ligand interactions influenced by conformational changes and membrane partitioning.

Purpose of the Study:

  • To investigate the temperature-dependent distribution and interaction of menthol with the TRPM8 channel.
  • To elucidate how temperature modulates menthol binding and TRPM8 activation.
  • To challenge traditional site-centric ligand binding models for polymodal ion channels.

Main Methods:

  • Flooding molecular dynamics simulations of TRPM8 in open and closed states.
  • Simulations were performed across a physiological temperature range.
  • Analysis of menthol distribution and interaction patterns within the protein-membrane environment.

Main Results:

  • Menthol distribution is temperature-dependent, shifting from intracellular/interfacial regions below 300 K to transmembrane regions above.
  • Menthol acts as a low-affinity, multisite ligand interacting across various TRPM8 domains.
  • Temperature-dependent occupancy patterns were shown to shift the TRPM8 open-closed equilibrium.

Conclusions:

  • Temperature regulates TRPM8 function by modulating menthol interactions at the protein-membrane interface, not just channel energetics.
  • Menthol's efficacy is determined by temperature-dependent ligand partitioning in polymodal ion channels.
  • This study provides molecular insights into menthol's modulation of TRPM8 activity.