Store-operated Ca²⁺ entry suppresses distention-induced ATP release from the urothelium

Abstract

Epithelial cells in the urinary bladder (urothelium) trigger sensory signals in micturition by releasing ATP in response to distention of the bladder wall. Our previous study revealed the distinct roles of extracellular Ca(2+) and the Ca(2+) stores in the endoplasmic reticulum (ER) in urothelial ATP release. In the present study, we investigated the regulation of urothelial ATP release by Ca(2+) influx from the extracellular space and Ca(2+) release from the ER using a distention assay of the mouse bladder wall in a small Ussing chamber. Stimulation of Ca(2+) release from the ER in the mucosal side of the bladder induced significant ATP release without distention. Blockade of the inositol 1,4,5-triphosphate receptor reduced distention-induced ATP release, suggesting that Ca(2+) release from the ER is essential for the induction of urothelial ATP release. On the other hand, blockade of store-operated Ca(2+) entry (SOCE) from the extracellular space significantly enhanced distention-induced ATP release. Thus Ca(2+) release from the ER causes urothelial ATP release and depletion of Ca(2+) stores in the ER, which in turn causes the depletion-inducing SOCE to suppress the amount of urothelial ATP released.

The regulation of distention-induced ATP release from urothelium by the adenylyl cyclase-cyclic AMP pathway

“…The urothelial ATP release assay was performed as described previously (22,23). In brief, isolated urinary bladders were opened vertically from the urethra to the apex.…”

“…stores in the ER, exerted an opposite, suppressive effect (23). Involvement of Ca 2+ implies that ATP ological range of pressure during urine storage; 50 μL of Krebs solution in the mucosal side of chamber was sampled before and after pressure application.…”

“…Knockout mice lacking TRPV1 or TRPV4 showed impairment of stretch-evoked increases in intracellular Ca 2+ and in ATP release from the urothelium (4,15). Furthermore, Ca 2+ release from the endoplasmic reticulum (ER) is involved in induction of urothelial ATP release (23). On the other hand, store-operated Ca 2+ entry, which is driven by depletion of Ca…”

Regulatory Effects of 5-Hydroxytryptamine Receptors on Voiding Function

“…Distention of the bladder wall during the phase of urine storage evokes a release of adenosine triphosphate (ATP) from the urothelium [37][38][39]. This activates purinergic P2X 3 receptors on afferent nerve terminals in the urinary bladder to transmit viscerosensory signals such as the extent of distention and/or bladder pain [40].…”

The role of ATP signalling in response to mechanical stimulation studied in T24 cells using new microphysiological tools

“…Some reports show an increase in intracellular Ca 2+ concentration before release of ATP, indicating that the mechanosensing is initiated by mechanosensitive, possibly Ca 2+ -conducting receptors. [39][40][41] These findings suggest that the release of ATP is an active secretion that requires an increase in intracellular Ca 2+ concentration to take place.…”