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TRPing on Cell Swelling - TRPV4 Senses It.

Trine L Toft-Bertelsen1, Nanna MacAulay1

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Summary

Transient receptor potential vanilloid 4 (TRPV4) channels sense cell swelling. This review explores how cell volume changes activate TRPV4 channels, impacting physiology and disease.

Keywords:
TRPV4 (transient receptor potential vanilloid 4)aquaporins (AQPs)osmo-sensingvolume regulationvolume-sensitive channels

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Area of Science:

  • Cell biology
  • Ion channel physiology
  • Molecular biophysics

Background:

  • Transient receptor potential vanilloid 4 (TRPV4) is a cation channel activated by diverse stimuli.
  • Cell swelling is a key regulator of TRPV4 activity, leading to channel activation.
  • Aquaporins (AQPs) facilitate swelling-dependent TRPV4 activation in specific experimental setups.

Purpose of the Study:

  • To review proposed mechanisms linking cell swelling to TRPV4 activation.
  • To present evidence for direct and indirect swelling-activation of TRPV4.
  • To clarify the role of TRPV4 as a cell volume sensor in physiology and pathophysiology.

Main Methods:

  • Literature review of studies on TRPV4 channel activation.
  • Analysis of experimental data on osmotic gradients and cell swelling.
  • Examination of molecular coupling events between cell volume and TRPV4.

Main Results:

  • TRPV4 activation is consistently observed with cell swelling, regardless of the underlying swelling mechanism.
  • Evidence supports both direct and indirect pathways for swelling-induced TRPV4 activation.
  • Aquaporin co-expression is crucial for rapid swelling-induced activation in certain experimental models.

Conclusions:

  • TRPV4 functions as a sensitive sensor of cellular volume increase.
  • Further research is needed to fully elucidate the molecular mechanisms and physiological relevance of TRPV4 swelling-activation.
  • Understanding TRPV4's role in volume homeostasis is critical for its implications in various diseases.