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Updated: May 27, 2026
11:53
Purification and Reconstitution of TRPV1 for Spectroscopic Analysis
Published on: July 3, 2018
A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels
David E Clapham1, Christopher Miller
1Department of Cardiology, Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital Boston, and Harvard Medical School, Boston, MA 02115, USA. dclapham@enders.tch.harvard.edu
Summary
Transient receptor potential (TRP) channels sense temperature. This study proposes that large changes in heat capacity during TRP channel opening explain their high temperature sensitivity, suggesting identical conformational changes for hot and cold sensing.
Area of Science:
- Neuroscience and biophysics
- Molecular and cellular biology
Background:
- Transient receptor potential (TRP) channels are crucial for thermosensation.
- Their high temperature sensitivity implies significant enthalpy changes during gating.
- The molecular basis for these enthalpy changes remains largely unknown.
Purpose of the Study:
- To propose a unifying mechanism for the temperature sensitivity of TRP channels.
- To explain the large enthalpy changes associated with TRP channel activation.
Main Methods:
- Thermodynamic principles applied to protein conformational changes.
- Analysis of heat capacity changes (ΔC(P)) during channel gating.
Main Results:
- A model is proposed where TRP channel gating involves substantial changes in molar heat capacity (ΔC(P)).
- This mechanism reconciles the thermodynamic requirements for both heat- and cold-activated TRP channels.
- The proposed mechanism is independent of specific gating details.
Conclusions:
- Large ΔC(P) changes provide a general explanation for the high temperature sensitivity of TRP channels.
- Hot- and cold-sensing TRP channels may utilize the same fundamental conformational changes.
- This framework offers a new perspective on thermosensation at the molecular level.
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