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Updated: Mar 27, 2026

Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
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Temperature-dependent gating pathways in TRPV3.

Guangyu Wang1,2

  • 1Department of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA, USA. gary.wang10@gmail.com.

Scientific Reports
|March 26, 2026
PubMed
Summary
This summary is machine-generated.

The heat capacity model explains both heat and cold activation in TRPV3 channels, even with inactivation. Tetrahydrocannabivarin (THCV) controls TRPV3 channel gating, showing temperature-dependent activation and inactivation.

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Ion Channel Physiology

Background:

  • The heat capacity model has successfully predicted temperature sensitivity in TRPV1-4 channels.
  • However, its applicability to TRPV3 channels, particularly concerning inactivation, remains unexamined.
  • TRPV3 shares similarities with TRPV1, suggesting a potential for mirrored thermal gating mechanisms.

Purpose of the Study:

  • To investigate the temperature-dependent structural changes and gating mechanisms of oxidized TRPV3 channels.
  • To determine the influence of tetrahydrocannabivarin (THCV) on TRPV3 structure, gating, and thermal sensitivity.
  • To validate the heat capacity model for TRPV3, considering both activation and inactivation processes.

Main Methods:

  • Characterization of temperature-dependent quaternary and tertiary structures of oxidized TRPV3.
  • Analysis of TRPV3 in the presence and absence of THCV at the vanilloid site.
  • Lipid-dependent gating pathway analysis and thermoring analyses.

Main Results:

  • Oxidized TRPV3 exhibited temperature-dependent activation and inactivation by THCV below 30 °C.
  • Above 30 °C, THCV binding released lipids, preventing inactivation.
  • Distinct cold and heat-evoked open states showed similar initial thermosensitivity, supporting symmetric activation.
  • Inactivation led to pore dilation and a tetramer-to-pentamer transition.

Conclusions:

  • The heat capacity model supports symmetric cold and heat activation in oxidized TRPV3, irrespective of subsequent inactivation.
  • THCV acts as a modulator of TRPV3 gating, with its effects being temperature-dependent.
  • TRPV3 inactivation involves distinct structural rearrangements, including pore dilation and oligomeric state changes.