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.