The TRPV4 Cation Channel Mediates Stretch-evoked Ca2+ Influx and ATP Release in Primary Urothelial Cell Cultures

• DOI: 10.1074/jbc.m109.020206
• Publication Date: 2009-06-17T00:12:57Z
• Authors: Tsutomu Mochizuki; Takaaki Sokabe; Isao Araki; Kayoko Fujishita; Koji Shibasaki; Kunitoshi Uchida; Keiji Naruse; Schuichi Koizumi; Masayuki Takeda; Makoto Tominaga
• Keywords: TRPV4; Ruthenium red; Urothelial Cell; Channel blocker

Transient receptor potential channels have recently been implicated in physiological functions a urogenital system. In this study, we investigated the role of transient vanilloid 4 (TRPV4) stretch sensing mechanism mouse primary urothelial cell cultures. The selective TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD) evoked Ca(2+) influx wild-type (WT) cells, but not TRPV4-deficient (TRPV4KO) cells. We established cell-stretch system to investigate stretch-evoked changes intracellular concentration and ATP release. Stretch stimulation increases speed- distance-dependent manner WT TRPV4KO however, increase response was significantly attenuated compared with that Stretch-evoked urothelium were partially reduced presence ruthenium red, broad TRP channel blocker, whereas cells did show such reduction. Potent release occurred following or 4alpha-PDD administration which dramatically suppressed Stretch-dependent almost completely eliminated red absence extracellular Ca(2+). These results suggest senses distension bladder urothelium, is converted an signal micturition reflex pathway during urine storage.