Functional role for Piezo1 in stretch-evoked Ca²⁺ influx and ATP release in urothelial cell cultures.
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 Ca(2+) 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 Ca(2+) 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.
From the Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898.
Tatsuya
T
Miyamoto
From the Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, tsutomu@yamanashi.ac.jp.
Tsutomu
T
Mochizuki
From the Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898.
Hiroshi
H
Nakagomi
From the Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898.
Satoru
S
Kira
the Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787.
Masaki
M
Watanabe
the Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787.
Yasunori
Y
Takayama
the Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, the Department of Physiological Sciences, Graduate University for Advanced Studies, Okazaki 444-8585, and.
Yoshiro
Y
Suzuki
the Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
Schuichi
S
Koizumi
From the Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898.
Masayuki
M
Takeda
the Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji, Okazaki, Aichi 444-8787, the Department of Physiological Sciences, Graduate University for Advanced Studies, Okazaki 444-8585, and tominaga@nips.ac.jp.
Makoto
M
Tominaga
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D017136:Ion Transport; D051379:Mice; D008810:Mice, Inbred C57BL; D050916:TRPV Cation Channels / Q000378:metabolism; D019459:Urothelium / Q000378:metabolism*
D007473:Ion Channels; C552920:Piezo1 protein, mouse; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D000255:Adenosine Triphosphate; D002118:Calcium
ATP; Calcium; Ion Channel; Mechanotransduction; Transient Receptor Potential Channels (TRP Channels)