title: Examining the role of mechanosensitive ion channels in pressure mechanotransduction in rat bladder urothelial cells.
abstract: Until recently, the bladder urothelium had been thought of only as a physical barrier between urine and underlying bladder tissue. Recent studies, however, have demonstrated that the urothelium is sensitive to mechanical stimuli and responds by releasing signaling molecules (NO, ATP). This study sought to investigate the role of select ion channels in urothelial cell (UC) pressure mechanotransduction. Using a custom-made pressure chamber, rat bladder UCs cultured on tissue culture plastic dishes were exposed to sustained hydrostatic pressure (5-20 cmH(2)O) for up to 30 min. When compared to the control, UCs exposed to 10 cmH(2)O (5 min), and 15 cmH(2)O (5 and 15 min), exhibited a significant (p < 0.05) increase in ATP release. In the absence of extracellular calcium, ATP release due to hydrostatic pressure was attenuated. Blocking the L-type voltage-gated channel with nifedipine during pressure exposure did not affect ATP release. However, blocking TRP channels, stretch-activated channels (SACs), and the epithelial sodium channel (ENaC) with ruthenium red, gadolinium chloride, and amiloride, respectively, all abolished hydrostatic pressure-evoked ATP release. These results have provided evidence for the first time that cultured UCs are sensitive to hydrostatic pressure in the physiologically relevant range. The results of this study also provide evidence that one or multiple mechanosensitive ion channels play a role in the mechanotransduction of hydrostatic pressure, which supports the view that not only tissue stretch or tension, but also pressure is an important parameter for mechanosensing of bladder fullness.
authors.affiliation: Department of Bioengineering, 301 Rhodes Engineering Research Center, Clemson University, Clemson, SC 29634-0905, USA.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Olsen
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Stover
authors.forename: Jiro
authors.initials: J
authors.lastname: Nagatomi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000166:cytology / Q000502:physiology*; D019459:Urothelium / Q000166:cytology / Q000502:physiology*
chemical_list: D007473:Ion Channels; D000255:Adenosine Triphosphate