TRPV4: A Physio and Pathophysiologically Significant Ion Channel

Abstract

Transient Receptor Potential (TRP) channels are a family of ion channels whose members are distributed among all kinds of animals, from invertebrates to vertebrates. The importance of these molecules is exemplified by the variety of physiological roles they play. Perhaps, the most extensively studied member of this family is the TRPV1 ion channel; nonetheless, the activity of TRPV4 has been associated to several physio and pathophysiological processes, and its dysfunction can lead to severe consequences. Several lines of evidence derived from animal models and even clinical trials in humans highlight TRPV4 as a therapeutic target and as a protein that will receive even more attention in the near future, as will be reviewed here.

Changes in cellular signaling patterns before and after stroke in the middle cerebral arteries of stroke prone spontaneously hypertensive rats

“…We therefore wished to investigate calcium regulation within the MCA. MCA vessels from the pre-stroke and post-stroke SHRsp rats were immunostained to detect the expression of TRPV4 (calcium channel), often associated with vascular remodelling & stiffening in vessels (24). TRPV4 primarily localized in the endothelial layer compared to the smooth muscle cell layer of the MCA ( Figure 5A).…”

“…Semiquantitative analysis of the mean gray value of TRPV4 staining showed a significantly lower expression of TRPV4 in post-stroke samples compared to pre-stroke samples ( Figure 5B). PKC is known to be an important mediator in regulating activation of TRPV4 channels in endothelial cells (24,25), which may reflect the reason for lower TRPV4 channels accompanying lower activation of PKC (Figure 1) in post-stroke MCA.…”

TRPing to the Point of Clarity: Understanding the Function of the Complex TRPV4 Ion Channel

“…The vanilloid subfamily of TRP channels can be further subdivided into six isoforms, of which the fourth member, TRPV4, has emerged as a regulator of cell function [ 7 ] in multiple tissues since being discovered in 2000 [ 8 , 9 ] as a homologue of the invertebrate Caenorhabditis elegans gene Osm-9. TRPV4 is characterized by multimodal activation properties that implicate it in a broad range of functions [ 10 ]. However, the mechanisms underlying activation of the channel by differing modalities remain largely elusive.…”

TRP Channels as Cellular Targets of Particulate Matter

“…TRPM8 is sensitive to cold temperatures and compounds that produce cooling sensations, such as menthol, eucalyptol and icilin [ 46 , 47 ]. Importantly, TRPV1, TRPV4, TRPA1 and TRPM8 are all reachable targets of PM, especially along the respiratory tract in epithelial cells, smooth muscle cells and sensory neurons, and have all been involved in the pathophysiology of the airways, e.g., irritation, inflammation and cough [ 48 , 49 , 50 ].…”