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Publication : Functional role for Piezo1 in stretch-evoked Ca²⁺ influx and ATP release in urothelial cell cultures.

First Author  Miyamoto T Year  2014
Journal  J Biol Chem Volume  289
Issue  23 Pages  16565-75
PubMed ID  24759099 Mgi Jnum  J:215940
Mgi Id  MGI:5607375 Doi  10.1074/jbc.M113.528638
Citation  Miyamoto T, et al. (2014) Functional role for Piezo1 in stretch-evoked Ca(2)(+) influx and ATP release in urothelial cell cultures. J Biol Chem 289(23):16565-75
abstractText  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.
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