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Transient receptor potential channels in sensory mechanisms of the lower urinary tract

Nature Reviews Urology volume 18, pages 139–159 (2021)Cite this article

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Abstract

Disruptions to sensory pathways in the lower urinary tract commonly occur and can give rise to lower urinary tract symptoms (LUTS). The unmet clinical need for treatment of LUTS has stimulated research into the molecular mechanisms that underlie neuronal control of the bladder and transient receptor potential (TRP) channels have emerged as key regulators of the sensory processes that regulate bladder function. TRP channels function as molecular sensors in urothelial cells and afferent nerve fibres and can be considered the origin of bladder sensations. TRP channels in the lower urinary tract contribute to the generation of normal and abnormal bladder sensations through a variety of mechanisms, and have demonstrated potential as targets for the treatment of LUTS in functional disorders of the lower urinary tract.

Key points

  • Transient receptor potential (TRP) channels are expressed throughout all layers of the bladder wall and their function is closely related to the location of expression.

  • High urothelial expression of TRPM4, TRPM7 and TRPV4 has been observed, the latter of which is considered to be a stretch sensor in urothelial cells.

  • TRPV1, TRPA1 and TRPM8 are expressed on afferent nerves in the bladder and are involved in changes in bladder function during inflammation (TRPV1 and TRPA1) or cold stimulation (TRPM8).

  • Despite involvement of TRP channels in animal models for overactive bladder, underactive bladder and cold-induced LUTS, translation to clinical applications remains limited.

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Fig. 1: Schematic representation of the shared structure of TRP channels.
Fig. 2: Schematic representation of TRP channels in excitable and non-excitable cells in the bladder wall.
Fig. 3: Single-cell transient receptor potential channel transcriptomics in mouse mucosa.
Fig. 4: Schematic representation of the bladder wall with the presumed cellular localization of TRP channels.

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Acknowledgements

This work was supported by grants from the Research Foundation — Flanders (FWO; G0A6113N), and the Research Council of KU Leuven (C1-TRPLe; T.V., and W.E.). W.E. is a senior clinical researcher of the Research Foundation-Flanders (FWO Vlaanderen).

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  1. Laboratory of Ion Channel Research, VIB Center for Brain & Disease Research, Leuven, and Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

    Matthias Vanneste, Andrei Segal & Thomas Voets

  2. Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium

    Wouter Everaerts

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W.E., M.V. and A.S. researched data for the article. W.E., M.V. and T.V. wrote the article and reviewed/edited the manuscript before submission. All authors contributed substantially to discussion of the content.

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Glossary

Afferent nerve

A nerve that conveys information from the organs to the central nervous system (as opposed to efferent nerves that send information from the central nervous system to the organs).

Agonist

A chemical compound that activates a receptor or ion channel.

Antagonist

A chemical compound that inhibits a receptor or ion channel.

Neurogenic inflammation

Inflammation caused by the release of inflammatory mediators from nerve endings.

Detrusor–sphincter dyssynergia

Detrusor contraction accompanied by involuntary contraction (instead of relaxation) of the urethral sphincter.

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Vanneste, M., Segal, A., Voets, T. et al. Transient receptor potential channels in sensory mechanisms of the lower urinary tract. Nat Rev Urol 18, 139–159 (2021). https://doi.org/10.1038/s41585-021-00428-6

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