Role of TREK-1 Potassium Channel in Bladder Overactivity After Partial Bladder Outlet Obstruction in Mouse

Purpose: Mouse models of partial bladder outlet obstruction cause bladder hypertrophy. Expression of a number of ion channels is altered in hypertrophic detrusor muscle, resulting in bladder dysfunction. We determined whether mechanosensitive TREK-1 channels are present in the murine bladder and whether their expression is altered in partial bladder outlet obstruction, resulting in abnormal filling responses. Materials and Methods: Partial bladder outlet obstruction was surgically induced in CD-1 mice and the mice recovered for 14 days. Cystometry was done to evaluate bladder pressure responses during filling at 25 mu l per minute in partial bladder outlet obstruction mice and sham operated controls. TREK-1 channel expression was determined at the mRNA and protein levels by quantitative reverse transcriptase-polymerase chain reaction and Western blotting, respectively, and localized in the bladder wall using immunohistochemistry. Results: Obstructed bladders showed about a 2-fold increase in weight vs sham operated bladders. TREK-1 channel protein expression on Western blots from bladder smooth muscle strip homogenates was significantly decreased in obstructed mice. Immunohistochemistry revealed a significant decrease in TREK-1 channel immunoreactivity in detrusor smooth muscle in obstructed mice. On cystometry the TREK-1 channel blocker L-methioninol induced a significant increase in premature contractions during filling in sham operated mice. L-methioninol had no significant effect in obstructed mice, which showed an overactive detrusor phenotype. Conclusions: TREK-1 channel down-regulation in detrusor myocytes is associated with bladder overactivity in a murine model of partial bladder outlet obstruction.