From urgency to frequency: facts and controversies of TRPs in the lower urinary tract

The members of transient receptor potential (TRP) superfamily of cationic ion channels represent universal sensors, which convert multiple exogenous and endogenous chemical and physical stimuli into electrical and functional cellular responses. TRPs are widely distributed in many different tissues, and expression of numerous TRP types has been reported in lower urinary tract (LUT) tissues, neuronal fibers innervating the bladder and urethra, and epithelial and muscular layers of the bladder and urethral walls, where they are mainly involved in nociception and mechanosensory transduction. As such, they represent attractive targets for treating LUT disorders. Although information on the functional significance of many of the TRP proteins in the LUT remains very limited, compelling evidence has accumulated for a pivotal role of TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 in normal and pathological LUT function, mainly as sensors of stretch and chemical irritation. Further studies into these and other TRPs in the LUT will facilitate the development of improved therapeutic strategies to target these channels in LUT disorders.