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Updated: Mar 20, 2026

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Molecular mechanism of menthol-induced TRPV5 channel inhibition

Angélica Méndez-Reséndiz1, José J De Jesús-Pérez2,3, Gisela E Rangel-Yescas1

  • 1Departamento de Fisiología, Facultad de Medicina, UNAM, Mexico City, Mexico.

Nature Communications
|March 19, 2026
PubMed

Insights

Menthol inhibits TRPV5 channels, crucial for calcium balance. Structural analysis reveals menthol binds to W583, offering a basis for developing new TRPV5 modulators.

Area of Science:

  • Molecular biology
  • Biophysics
  • Pharmacology

Background:

  • Transient Receptor Potential Vanilloid 5 (TRPV5) channels are vital for calcium homeostasis.
  • Dysregulation of TRPV5 is linked to various diseases.

Purpose of the Study:

  • To investigate menthol's effect on TRPV5 channels.
  • To elucidate the structural basis of menthol-TRPV5 interaction.

Main Methods:

  • Electrophysiology to study ion channel function.
  • Single-particle cryo-electron microscopy (cryo-EM) for structural determination.

Main Results:

  • Menthol identified as a potent inhibitor of TRPV5 channels.
  • Menthol blocks TRPV5 ion conduction via a slow blocker mechanism.
  • Cryo-EM structure reveals menthol binding to the W583 residue in TRPV5.

Conclusions:

  • Menthol is a novel modulator of TRPV5 channels.
  • The W583 residue is critical for menthol binding and channel function.
  • Menthol serves as a potential scaffold for designing new TRPV5-targeting drugs.

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