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Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
Published on: December 31, 2013
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Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function.
Liying Zhang1,2,3, Charlotte Simonsen1, Lucie Zimova4
1Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Nature Communications
|December 5, 2022
Summary
The phytocannabinoid Δ9-tetrahydrocannabiorcol (C16) and probenecid stimulate TRPV2 channel activity and histamine release. Researchers identified a novel cannabinoid binding site on TRPV2, modulated by probenecid.
Area of Science:
- Molecular pharmacology
- Ion channel function
- Cryo-electron microscopy
Background:
- TRPV2 is a temperature-sensitive ion channel with poorly understood pharmacology.
- Understanding TRPV2 modulation is crucial for its role in normal and pathological processes.
Purpose of the Study:
- To investigate the modulatory effects of the phytocannabinoid Δ9-tetrahydrocannabiorcol (C16) and probenecid on TRPV2 channel activity.
- To elucidate the molecular mechanisms underlying TRPV2 activation by these ligands.
Main Methods:
- Calcium imaging
- Patch-clamp electrophysiology
- Cryo-electron microscopy (cryo-EM)
Main Results:
- C16 and probenecid synergistically enhance TRPV2 activity, leading to histamine release from mast cells.
- Cryo-EM revealed distinct conformational changes induced by C16 and probenecid.
- C16 binds to the vanilloid pocket, a novel cannabinoid binding site, distinct from other known ligands.
- Probenecid allosterically influences the C16 binding site.
Conclusions:
- A new allosterically regulated cannabinoid binding site on TRPV2 has been identified.
- This molecular insight into TRPV2 ligand modulation deepens the understanding of its physiological and pathophysiological roles.
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