Long-term follow-up of TREK-1 KO mice reveals the development of bladder hypertrophy and impaired bladder smooth muscle contractility with age

This study aimed to characterize the long-term effects of TREK-1 on bladder function by using global and smooth muscle specific TREK-1 knock out (KO) mice. Bladder morphology, bladder smooth muscle (BSM) contractility, and voiding patterns were evaluated up to 12 months of age. Both sexes were included in this study to probe the potential sex differences. Smooth muscle specific TREK-1 KO mice were used to distinguish the effects of TREK-1 downregulation in BSM from the neural pathways involved in the control of bladder contraction and relaxation. TREK-1 KO mice developed enlarged urinary bladders (by 60.0% for males and by 45.1% for females at 6m, p<0.001 to age-matched control group), and had a significantly increased bladder capacity (by 137.7% at 12m, p<0.0001) and compliance (by 73.4% at 12m, p<0.0001). Bladder strips isolated from TREK-1 KO mice exhibited a decreased contractility (peak force after KCl at 6m was 1.6±0.7 N/g in comparison to 3.4±2.0 N/g in the control group, p=0.0005). The lack of TREK-1 channels exclusively in BSM did not replicate the bladder phenotype observed in TREK-1 KO mice, suggesting a strong neurogenic origin of TREK-1-related bladder dysfunction.PMID:38601986 | DOI:10.1152/ajprenal.00382.2023
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Source Type: research