Modulation of urinary bladder paracellular permeability by stretch

Abstract

In response to bladder filling and voiding, umbrella cells undergo changes in cell‐shape and vesicular trafficking. However, it is not known how filling/voiding impact paracellular transport in these cells. To investigate how changes in umbrella cell stretch affect paracellular permeability, bladder mucosa was mounted in Ussing chambers and studied under current clamp conditions. In this system the transepithelial resistance (TER) was dependent on whether the tissue was bowed outwards, simulating filling, or bowed inwards as observed during voiding when the epithelium is refolded. Outward bowing provoked by an increase in mucosal hydrostatic pressure of ~1 cm of water caused a decrease in junctional resistance from 21.1 ± 8.5 to 1.8 ± 0.4 kΩ.cm2. These effects were reversible and dependent on the applied force. The integrity of the tight junctions (TJ) was assessed by examining the distribution of ruthenium red (RR) added to the mucosal surface of the tissue and examined by electron microscopy. The TJ appeared intact and no RR was found along the basolateral surface of the cells during experimental filling. Finally, depletion of extracellular Ca2+ by EGTA completely disrupted the TER of control, but not of stretched uroepithelium, indicating a change in the junctional barrier. In summary, our results indicate that filling and voiding impacts the junctional complex of umbrella cells.