ACTIVATION OF INTERSTITIAL CELLS EXPRESSING TRANSIENT RECEPTOR POTENTIAL VANILLOID TYPE 1 CHANNELS INCREASES MECHANICAL COMPLIANCE IN THE FEMALE MOUSE URINARY BLADDER

Transient receptor potential ion channel vanilloid type 1 (TRPV1) channels are nonselective cation channels involved in nociception and are activated by high temperatures and anandamide. They are distributed throughout the urinary bladder in afferent nerves and vascular smooth muscle cells. However, their function in non-neuronal bladder cells, specifically interstitial cells, is controversial and the exact role of TRPV1 channels in micturition remains unknown. Furthermore, the prototypical agonist capsaicin activates but rapidly desensitizes TRPV1 channels, making prolonged activation difficult. The development of “Designer Receptors Exclusively Activated by Designer Drugs” (Gq-DREADD) mice allows for selective activation of TRPV1-positive cells with clozapine N-oxide (CNO). Thus, we expressed Gq-DREADD in all TRPV1-positive cells and measured ex vivo bladder pressure, volume, geometry, and biomechanics. We hypothesized that activation of TRPV1-expressing interstitial cells in the female murine urinary bladder increases mechanical compliance and transient pressure events/micromotions while decreasing mechanical stress and stretch.
TRPV1-DREADD mice were created by crossing TRPV1-Cre mice with B6N;129-Tg(CAG-CHRM3*,-mCitrine)1Ute/J mice. Urinary bladders from female mice (ages 27-29 weeks) were cannulated on the Pentaplanar Reflected Image Macroscopy System to simultaneously record intravesical pressure, geometry, and infused volume during ex vivo bladder filling (0 - 30 mmHg). Nerve activation was prevented using tetrodotoxin (TTX) (1 uM) before addition of CNO (500 nM). Bladder compliance was unaltered by TTX; however, CNO increased bladder compliance in the presence of TTX. Micromotions, transient pressure events, and stiffness were unchanged, suggesting TRPV1+ interstitial cells may play a key role in regulating bladder compliance without affecting smooth muscle excitability.