TRPV4 | Transient Receptor Potential Cation Channel Subfamily V Member 4

TRPV4 is a non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity exhibiting an outward rectification. It is activated by exposure to hypotonicity within the physiological range as well as by heat, low pH, citrate and phorbol esters. An increase of intracellular Ca²⁺ potentiates currents. The channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism.

Gene:
TRPV4

Human Protein:
UniProt Q9HBA0

Tissue:
Trachea, kidney, liver, spleen, skin, brain, PNS, heart

Function/ Application:
TRPV4 has been found to be involved in multiple phsiological functions, as the regulation of systemic osmotic pressure in the brain, the skin barrier, pain, osmosensation, homeostasis. In the vascular endothelium, it contributes to intracellular Ca²⁺ homeostasis and regulation of cell volume while responding to mechanical stresses on the vasculature. It is crucially for the function of the cardiac, respiratory, urinary, skeletal, and digestive systems, as well as in the central and peripheral nervous systems.

Pathology:
Brachyolmia 3 (BCYM3), Spondylometaphyseal dysplasia Kozlowski type (SMDK), Metatropic dysplasia (MTD), Neuronopathy, distal hereditary motor, 8 (HMN8), Charcot-Marie-Tooth disease 2C (CMT2C), Scapuloperoneal spinal muscular atrophy (SPSMA), Spondyloepiphyseal dysplasia Maroteaux type (SEDM), Parastremmatic dwarfism (PSTD), Digital arthropathy-brachydactyly, familial (FDAB), Avascular necrosis of the femoral head, primary 2 (ANFH2)

Interaction:
Calmodulin, Map7, Src family Tyr protein kinases (LYN, SRC, FYN, HCK, LCK and YES), CTNNB1, PACSIN1, PACSIN2, PACSIN3, ITPR3, AQP5, ANO1, PKD2, and is part of the complex containing containing MLC1, AQP4, HEPACAM and ATP1B1.

Modulator:
Cannabidiol, Resiniferatoxin, GSK1016790A, RN1747, 4α-PDD, GSK2193874, HC067047, La³⁺, Gd³⁺, ruthenium red

Assays:
Patch Clamp: whole cell, temperature control

Recommended Reviews:
International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels., Pharmacol Rev 55(4):591-6 Clapham, et al. 2003
TRPV4: Molecular Conductor of a Diverse Orchestra, Physiological Reviews 96(3):911-973 John P.M White et al. 2016