Mp03-07 the lack of mechanosensitive trek-1 channel mimics the development of aging-related bladder phenotypes in mice

You have accessJournal of UrologyCME1 Apr 2023MP03-07 THE LACK OF MECHANOSENSITIVE TREK-1 CHANNEL MIMICS THE DEVELOPMENT OF AGING-RELATED BLADDER PHENOTYPES IN MICE Alison Xiaoqiao Xie, Nao Iguchi, and Anna Malykhina Alison Xiaoqiao XieAlison Xiaoqiao Xie More articles by this author , Nao IguchiNao Iguchi More articles by this author , and Anna MalykhinaAnna Malykhina More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous animal and human studies have confirmed that the potassium channel subfamily K member 2 (TREK-1), a member of two-pore domain mechanosensitive K+ channels (K2P), acts as a mechanosensor in the urinary bladder. We reported that TREK-1 is a predominantly expressed K2P channel in the human detrusor, and its expression and function are altered in patients with idiopathic detrusor overactivity (DO). TREK-1 expression in the peripheral organs and in the nervous system also declines during aging. This study aimed to investigate the role of TREK-1-related mechanosensitivity in the detrusor in aging mice. METHODS: Bladder histology, detrusor contractility, and voiding function were investigated in adult (3, 6, 9 and 12 months old) TREK-1 KO mice of both sexes and age-matched wildtype controls. Bladder weight, detrusor smooth muscle (DSM) thickness, and collagen content were compared between the groups using paraffin-embedded bladder samples. Bladder strip assay was used to evaluate detrusor muscle contractility and nerve-induced bladder contractions. Voiding spot assay (VSA) and awake cystometry recordings were performed to assess micturition patterns in vivo. RESULTS: Increased bladder weight and bladder wall thickness were observed in TREK-1 KO mice of both sexes, starting as early as at 6-month-old. and threshold volume in cystometry recordings. In comparison to age- and sex-matched controls, bladder strips isolated from TREK-1 KO mice showed significantly decreased DSM contractility including contractile responses to electric field stimulation and cholinergic receptor activation. Interestingly, while the peak forces of evoked DSM contractions decreased with aging in control mice, TREK-1 KO animals at 6-12 month-old displayed DSM contractility that was lower than in 12-month-old control animals. Increased numbers of non-voiding contractions were observed in both sexes of TREK-1 KO mice, whereas the bladder capacity, intermicturition interval, and micturition threshold volume were significantly increased in comparison to age-matched controls. CONCLUSIONS: In summary, the lack of TREK-1 expression in adult mice significantly increased a number of functional changes typically observed in underactive bladders with detrusor overactivity, including increases in bladder size, weight, capacity, and a significant decrease in DSM contractility. Our findings suggest that decreased TREK-1 expression may mimic the development of age-related voiding phenotypes in mice. Source of Funding: DK095817 (Malykhina), DK116648 (Malykhina) and Department of Surgery Academic Enrichment Fund (Xie) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e23 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alison Xiaoqiao Xie More articles by this author Nao Iguchi More articles by this author Anna Malykhina More articles by this author Expand All Advertisement PDF downloadLoading ...