Emerging roles of the TRPV4 channel in bladder physiology and dysfunction

The transient receptor potential vanilloid type 4, TRPV4, is a polymodal cation channel which can be activated by diverse stimuli including mechanical, thermal and chemical cues. In the urinary bladder, TRPV4 is not only abundantly expressed in the urothelium but may also be localized in subepithelium, detrusor smooth muscles and afferent neurons. Emerging evidence indicates that the TRPV4 channel plays a sensory role in the uroepithelium, where it may regulate the release of sensory mediators such as ATP, which in turn modulates afferent nerve activity in response to bladder filling during the urination cycle. TRPV4 may also directly regulate detrusor contractility and the urothelial barrier function. Altered TRPV4 expression has been detected in various pathological bladder conditions. As such, TRPV4 may be a promising therapeutic target for bladder dysfunctions. figure legend TRPV4 is located at multiple cellular elements of the bladder wall, where it participates in sensory transduction and regulation of the urothelial barrier function and detrusor activity. Altered TRPV4 expression or activity may cause impairments in these important physiological processes, contributing to the pathophysiology of bladder dysfunctions. Either TRPV4 agonists or antagonists may potentially be exploited for treatment of different bladder conditions.