- The Transient Receptor Potential Vanilloid (TRPV) channels are a subfamily of the TRP channel superfamily, notable for their diverse roles in sensory physiology and cellular homeostasis.
- These channels are non-selective cation channels that are primarily permeable to calcium (Ca²⁺), and they are responsive to a wide range of stimuli including temperature changes, osmotic stress, mechanical forces, and chemical ligands.
- TRPV channels are best known for their involvement in thermosensation and pain perception, though they also play significant roles in osmoregulation, epithelial transport, and bone metabolism.
- The TRPV subfamily comprises six members: TRPV1 through TRPV6. TRPV1–TRPV4 are temperature-sensitive and often referred to as “thermoTRPs,” whereas TRPV5 and TRPV6 are highly calcium-selective and involved mainly in calcium absorption and homeostasis. TRPV1, the founding member of the subfamily, is activated by noxious heat (>43°C), protons, and vanilloid compounds such as capsaicin, the active component in chili peppers. TRPV2 is activated by even higher temperatures (>52°C) and is expressed in various tissues, including immune cells and cardiac muscle, although its exact physiological roles remain under investigation. TRPV3 and TRPV4 respond to warm temperatures (33–39°C and 27–35°C, respectively) and are also sensitive to osmotic and mechanical stress.
- Structurally, TRPV channels share the general architecture of TRP channels, consisting of six transmembrane segments with a pore loop between the fifth and sixth segments. The intracellular N- and C-termini contain several regulatory domains, including ankyrin repeat domains, which facilitate protein–protein interactions and channel modulation. TRPV1–TRPV4 can form both homomeric and heteromeric channels, which contributes to functional diversity in different tissue types. In contrast, TRPV5 and TRPV6 are primarily expressed in epithelial cells of the kidney and intestine, respectively, where they function as homotetramers to mediate transcellular calcium transport critical for systemic calcium balance.
- Functionally, TRPV channels serve critical roles in both sensory and non-sensory systems. In the peripheral nervous system, TRPV1 is essential for detecting noxious heat and inflammatory pain, making it a major target in the development of analgesic drugs. TRPV4, expressed in sensory neurons and epithelial cells, participates in mechanotransduction and osmosensation, and has been implicated in inflammatory responses, edema, and neuropathic pain. In non-neuronal tissues, TRPV5 and TRPV6 regulate calcium absorption, playing crucial roles in bone remodeling, hormone secretion, and maintenance of serum calcium levels. Dysregulation of TRPV channels has been associated with numerous disorders, including chronic pain, neurodegenerative diseases, osteoporosis, cancer, and kidney stone formation.
