Functional Role for Piezo1 in Stretch-evoked Ca2+ Influx and ATP Release in Urothelial Cell Cultures

• Published in: The Journal of biological chemistry Vol. 289; no. 23; pp. 16565 - 16575
• Main Authors: Miyamoto, Tatsuya, Mochizuki, Tsutomu, Nakagomi, Hiroshi, Kira, Satoru, Watanabe, Masaki, Takayama, Yasunori, Suzuki, Yoshiro, Koizumi, Schuichi, Takeda, Masayuki, Tominaga, Makoto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.06.2014; American Society for Biochemistry and Molecular Biology
• Subjects: Adenosine Triphosphate - metabolism; Animals; ATP; Calcium; Calcium - metabolism; Cell Biology; Cells, Cultured; Humans; Ion Channel; Ion Channels - physiology; Ion Transport; Mechanotransduction; Mice; Mice, Inbred C57BL; Transient Receptor Potential Channels (TRP Channels); TRPV Cation Channels - metabolism; Urothelium - metabolism; Mechanotransduction; Ion Channel; Calcium; Transient Receptor Potential Channels (TRP Channels); ATP
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.M113.528638

The urothelium is a sensory structure that contributes to mechanosensation in the urinary bladder. Here, we provide evidence for a critical role for the Piezo1 channel, a newly identified mechanosensory molecule, in the mouse bladder urothelium. We performed a systematic analysis of the molecular and functional expression of Piezo1 channels in the urothelium. Immunofluorescence examination demonstrated abundant expression of Piezo1 in the mouse and human urothelium. Urothelial cells isolated from mice exhibited a Piezo1-dependent increase in cytosolic Ca2+ concentrations in response to mechanical stretch stimuli, leading to potent ATP release; this response was suppressed in Piezo1-knockdown cells. In addition, Piezo1 and TRPV4 distinguished different intensities of mechanical stimulus. Moreover, GsMTx4, an inhibitor of stretch-activated channels, attenuated the Ca2+ influx into urothelial cells and decreased ATP release from them upon stretch stimulation. These results suggest that Piezo1 senses extension of the bladder urothelium, leading to production of an ATP signal. Thus, inhibition of Piezo1 might provide a promising means of treating bladder dysfunction. The Piezo1 channel was recently identified as a genuine mechanosensor in mammalian cells. Urothelial cells exhibited a Piezo1-dependent increase in cytosolic Ca2+ concentrations in response to mechanical stretch stimuli, leading to ATP release. Piezo1 senses extension of the bladder urothelium, which is converted into an ATP signal. Inhibition of Piezo1 might provide a new treatment for bladder dysfunction.