Research on the afferent transduction in the lower urinary tract

我们对Piezo 1通道在尿路上皮中的分子和功能表达进行了系统的分析，免疫荧光检测显示Piezo 1在小鼠和人尿路上皮中有丰富的表达。从小鼠分离的尿路上皮细胞表现出Piezo 1依赖性增加胞浆Ca 2+浓度响应机械拉伸刺激，导致有效的ATP释放，这种反应被抑制在Piezo 1敲低细胞。此外，Piezo 1和TRPV 4还能区分不同强度的机械刺激，而牵张激活通道抑制剂GsMTx 4能抑制牵张刺激时细胞内Ca ~（2+）内流和ATP释放。这些结果表明，Piezo 1感觉膀胱尿道扩张，导致ATP信号的产生。因此，抑制Piezo 1可能提供治疗膀胱功能障碍的有希望的手段。

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.