Document Type
Article
Publication Date
5-21-2019
Identifier
DOI: 10.1186/s12894-019-0475-3; PMCID: PMC6528348
Abstract
BACKGROUND: Previously published results from our laboratory identified a mechano-gated two-pore domain potassium channel, TREK-1, as a main mechanosensor in the smooth muscle of the human urinary bladder. One of the limitations of in vitro experiments on isolated human detrusor included inability to evaluate in vivo effects of TREK-1 on voiding function, as the channel is also expressed in the nervous system, and may modulate micturition via neural pathways. Therefore, in the present study, we aimed to assess the role of TREK-1 channel in bladder function and voiding patterns in vivo by using TREK-1 knockout (KO) mice.
METHODS: Adult C57BL/6 J wild-type (WT, N = 32) and TREK-1 KO (N = 33) mice were used in this study. The overall phenotype and bladder function were evaluated by gene and protein expression of TREK-1 channel, in vitro contractile experiments using detrusor strips in response to stretch and pharmacological stimuli, and cystometry in unanesthetized animals.
RESULTS: TREK-1 KO animals had an elevated basal muscle tone and enhanced spontaneous activity in the detrusor without detectable changes in bladder morphology/histology. Stretch applied to isolated detrusor strips increased the amplitude of spontaneous contractions by 109% in the TREK-1 KO group in contrast to a 61% increase in WT mice (p ≤ 0.05 to respective baseline for each group). The detrusor strips from TREK-1 KO mice also generated more contractile force in response to electric field stimulation and high potassium concentration in comparison to WT group (p ≤ 0.05 for both tests). However, cystometric recordings from TREK-1 KO mice revealed a significant increase in the duration of the intermicturition interval, enhanced bladder capacity and increased number of non-voiding contractions in comparison to WT mice.
CONCLUSIONS: Our results provide evidence that global down-regulation of TREK-1 channels has dual effects on detrusor contractility and micturition patterns in vivo. The observed differences are likely due to expression of TREK-1 channel not only in detrusor myocytes but also in afferent and efferent neural pathways involved in regulation of micturition which may underly the "mixed" voiding phenotype in TREK-1 KO mice.
Journal Title
BMC urology [electronic resource]
Volume
19
Issue
1
First Page
40
Last Page
40
MeSH Keywords
Animals; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle Contraction; Potassium Channels, Tandem Pore Domain; Urinary Bladder; Urination
Keywords
Detrusor mechanosensitivity; Micturition cycle; TREK-1 channel; Urinary bladder; Voiding
Recommended Citation
Pineda RH, Hypolite J, Lee S, et al. Altered detrusor contractility and voiding patterns in mice lacking the mechanosensitive TREK-1 channel. BMC Urol. 2019;19(1):40. Published 2019 May 21. doi:10.1186/s12894-019-0475-3
Comments
Grant support
his article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Publisher's Access: https://doi.org/10.1186/s12894-019-0475-3