TRPV4 is expressed by enteric glia and muscularis macrophages of the colon but does not play a prominent role in colonic motility.

Background

Mechanosensation is an important trigger of physiological processes in the gastrointestinal tract. Aberrant responses to mechanical input are associated with digestive disorders, including visceral hypersensitivity. Transient Receptor Potential Vanilloid 4 (TRPV4) is a mechanosensory ion channel with proposed roles in visceral afferent signaling, intestinal inflammation, and gut motility. While TRPV4 is a potential therapeutic target for digestive disease, current mechanistic understanding of how TRPV4 may influence gut function is limited by inconsistent reports of TRPV4 expression and distribution.

Methods

In this study we profiled functional expression of TRPV4 using Ca

Results

The TRPV4 agonist GSK1016790A evoked Ca

Conclusions

We reveal a previously unappreciated role for TRPV4 in the initiation of distension-evoked colonic motility. These observations provide new insights into the functional role of TRPV4 activation in the gut, with important implications for how TRPV4 may influence critical processes including inflammatory signaling and motility.

Summary

TRPV4 is expressed by equivalent cell types in the rodent and primate (monkey and human) colon. This mechanosensitive ion channel has proposed roles in inflammation, visceral afferent signaling, and colonic motility.New analysis methods were developed to examine cellular communication in the enteric glial network. This approach revealed new insights into inflammation-associated changes in glial connectivity.New roles for TRPV4 in transduction of distension-evoked responses in the colon and colonic motility were identified.

Key findings

We have defined the cell types that functionally express TRPV4 in the gut wall. These include enteric glia, endothelia of blood and lymphatic vessels, mMac, and extrinsic afferent nerves. TRPV4- dependent Ca