Bladder afferent sensitivity in wild‐type and TRPV1 knockout mice

• DOI: 10.1113/jphysiol.2007.139147
• Publication Date: 2007-07-13T01:07:58Z
• Authors: D. Daly; W. Rong; R. Chess‐Williams; C. Chapple; D. Grundy
• Keywords: Capsazepine; TRPV; Knockout mouse; Resiniferatoxin; Capsaicin

Understanding bladder afferent pathways may reveal novel targets for therapy of lower urinary tract disorders such as overactive syndrome and cystitis. Several potential candidate molecules have been postulated playing a significant role in function. One is the transient receptor vanilloid 1 (TRPV1) ion channel. Mice lacking TRPV1 channel altered micturition thresholds suggesting that channels play detection filling. The aim this study was therefore to investigate receptors controlling sensitivity mouse using pharmacological blockade genetic deletion Multiunit activity recorded vitro from afferents taken wild-type (TRPV+/+) mice knockout (TRPV1-/-) mice. In preparations, ramp distension maximal pressure 40 mmHg produced graded increase activity. Bath application antagonist capsazepine (10 mum) caused attenuation discharge TRPV1+/+ Afferent responses were significantly attenuated TRPV1-/- which intravesical hydrochloric acid (50 mm) capsaicin microm) also blunted. Altered mechanosensitivity occurred absence any changes pressure-volume relationship during filling indicating not secondary change compliance. Single-unit analysis used classify individual into low-threshold high-threshold fibres. Low threshold compared littermates while surprisingly high unchanged. While are considered be mechanically gated, present demonstrates clear excitability particularly low afferents. This suggests an important normal