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TRPV4 calcium entry channel: a paradigm for gating diversity
Bernd Nilius1, Joris Vriens, Jean Prenen
1Laboratorium voor Fysiologie, KU Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium. Bernd.Nilius@med.kuleuven.ac.be
American Journal of Physiology. Cell Physiology
|January 7, 2004
Summary
The Transient Receptor Potential Vanilloid 4 (TRPV4) channel exhibits diverse gating mechanisms, responding to various physical and chemical stimuli. This review highlights TRPV4
Area of Science:
- Molecular biology
- Cell physiology
- Ion channel research
Background:
- The Transient Receptor Potential (TRP) superfamily includes cation channels crucial for cellular signaling.
- The vanilloid receptor-1 (VR1), now known as TRPV1, is the first identified member of the TRPV subgroup.
- The TRPV subgroup comprises six mammalian channels that mediate Ca2+ influx in response to diverse stimuli.
Purpose of the Study:
- To review and summarize the known gating mechanisms of TRPV4.
- To present TRPV4 as a model for understanding gating diversity within the TRPV channel subfamily.
Main Methods:
- Literature review of studies on TRPV4.
- Analysis of sequence identity and functional data comparing TRPV4 to other TRPV channels.
Main Results:
- TRPV4 shares 45% sequence identity with TRPV1.
- TRPV4 displays remarkable gating promiscuity, activated by hypotonic cell swelling, heat, and synthetic 4alpha-phorbols.
- Endogenous activators of TRPV4 include arachidonic acid (AA), anandamide, 2-AG, and AA metabolites like epoxyeicosatrienoic acids.
Conclusions:
- TRPV4 exemplifies the broad range of stimuli that can gate TRPV channels.
- Understanding TRPV4's diverse activation pathways is key to deciphering its physiological roles.