Novel regulatory mechanism in human urinary bladder: central role of transient receptor potential melastatin 4 channels in detrusor smooth muscle function

American Journal of Physiology. Cell Physiology
Kiril L HristovGeorgi V Petkov

Abstract

Transient receptor potential melastatin 4 (TRPM4) channels are Ca(2+)-activated nonselective cation channels that have been recently identified as regulators of detrusor smooth muscle (DSM) function in rodents. However, their expression and function in human DSM remain unexplored. We provide insights into the functional role of TRPM4 channels in human DSM under physiological conditions. We used a multidisciplinary experimental approach, including RT-PCR, Western blotting, immunohistochemistry and immunocytochemistry, patch-clamp electrophysiology, and functional studies of DSM contractility. DSM samples were obtained from patients without preoperative overactive bladder symptoms. RT-PCR detected mRNA transcripts for TRPM4 channels in human DSM whole tissue and freshly isolated single cells. Western blotting and immunohistochemistry with confocal microscopy revealed TRPM4 protein expression in human DSM. Immunocytochemistry further detected TRPM4 protein expression in DSM single cells. Patch-clamp experiments showed that 9-phenanthrol, a selective TRPM4 channel inhibitor, significantly decreased the transient inward cation currents and voltage step-induced whole cell currents in freshly isolated human DSM cells. In current-clamp...Continue Reading

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Citations

Aug 9, 2016·Pflügers Archiv : European journal of physiology·Ayu IsogaiHikaru Hashitani
Jul 29, 2018·Naunyn-Schmiedeberg's Archives of Pharmacology·F Aura KullmannLori A Birder
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Jul 7, 2020·American Journal of Physiology. Renal Physiology·John Malysz, Georgi V Petkov
Nov 19, 2019·Neurourology and Urodynamics·Christopher Henry FryMarcus J Drake
Oct 13, 2020·Frontiers in Physiology·John Malysz, Georgi V Petkov
Feb 5, 2021·Nature Reviews. Urology·Matthias VannesteWouter Everaerts

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