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

Matsumoto-Miyai K, Kagase A, Yamada E, Yoshizumi M, Murakami M, Ohba T, Kawatani M. Store-operated Ca2+ entry suppresses distention-induced ATP release from the urothelium. Am J Physiol Renal Physiol 300: F716-F720, 2011. First published December 15, 2010; doi:10.1152/ajprenal.00512.2010.-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 Ca2+ and the Ca2+ stores in the endoplasmic reticulum (ER) in urothelial ATP release. In the present study, we investigated the regulation of urothelial ATP release by Ca2+ influx from the extracellular space and Ca2+ release from the ER using a distention assay of the mouse bladder wall in a small Ussing chamber. Stimulation of Ca2+ 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 Ca2+ release from the ER is essential for the induction of urothelial ATP release. On the other hand, blockade of store-operated Ca2+ entry (SOCE) from the extracellular space significantly enhanced distention-induced ATP release. Thus Ca2+ release from the ER causes urothelial ATP release and depletion of Ca2+ stores in the ER, which in turn causes the depletion-inducing SOCE to suppress the amount of urothelial ATP released.