Role of TREK-1 potassium channel in bladder overactivity after partial bladder outlet obstruction in mouse.
OBJECTIVE
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.


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 microl 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.
Baker
Salah A
SA
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Hatton
William J
WJ
Han
Junguk
J
Hennig
Grant W
GW
Britton
Fiona C
FC
Koh
Sang Don
SD
D000818:Animals; D005260:Female; D051379:Mice; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*; D001748:Urinary Bladder Neck Obstruction / Q000150:complications*; D053201:Urinary Bladder, Overactive / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1