Altered detrusor contractility and voiding patterns in mice lacking the mechanosensitive TREK-1 channel

Area of Science:

• Urology
• Physiology
• Molecular Biology

Background:

• TREK-1 (two-pore domain potassium channel) identified as a key mechanosensor in human bladder smooth muscle.
• In vitro studies limited in assessing in vivo voiding function due to TREK-1's neural expression.

Purpose of the Study:

• To investigate the in vivo role of TREK-1 channels in bladder function and micturition patterns.
• To evaluate the effects of TREK-1 knockout (KO) on voiding using a mouse model.

Main Methods:

• Utilized adult C57BL/6J wild-type (WT) and TREK-1 KO mice.
• Assessed phenotype and bladder function via gene/protein expression, in vitro detrusor strip contractility (stretch, electrical stimulation, high K+), and cystometry in unanesthetized animals.

Main Results:

• TREK-1 KO mice exhibited elevated basal detrusor tone and enhanced spontaneous activity.
• Detrusor strips from KO mice showed increased contractile force in response to stretch, electrical field stimulation, and high potassium.
• In vivo cystometry revealed longer intermicturition intervals, increased bladder capacity, and more non-voiding contractions in KO mice.

Conclusions:

• Global down-regulation of TREK-1 channels has dual effects on detrusor contractility and in vivo micturition.
• Observed "mixed" voiding phenotype in KO mice likely results from TREK-1 expression in both detrusor myocytes and neural pathways regulating micturition.