MP38-09 THE LACK OF MECHANOSENSITIVE K2P CHANNEL IS ASSOCIATED WITH MIXED VOIDING PHENOTYPE IN MICE

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II1 Apr 2018MP38-09 THE LACK OF MECHANOSENSITIVE K2P CHANNEL IS ASSOCIATED WITH MIXED VOIDING PHENOTYPE IN MICE Ricardo Pineda, Joseph Hypolite, Sanghee Lee, Alonso Carrasco, Nao Iguchi, Randall B Meacham, and Anna P Malykhina Ricardo PinedaRicardo Pineda More articles by this author , Joseph HypoliteJoseph Hypolite More articles by this author , Sanghee LeeSanghee Lee More articles by this author , Alonso CarrascoAlonso Carrasco More articles by this author , Nao IguchiNao Iguchi More articles by this author , Randall B MeachamRandall B Meacham More articles by this author , and Anna P MalykhinaAnna P Malykhina More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1236AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder capacity is defined by the physiological response of the bladder wall to stretch. We previously reported that compliance of the bladder wall during storage phase of the micturition cycle in the human urinary bladder is regulated by a mechanosensitive TREK-1 channel, a member of the K2P potassium channel family. The use of isolated human tissue limited evaluation of in vivo role of TREK-1 on voiding function as these channels are also expressed in the nervous system and may modulate micturition via neural pathways. Therefore, in this study, we aimed to assess the role of TREK-1 channels in bladder contractility and voiding using TREK-1 knockout (KO) mice. We hypothesized that absence of TREK-1 expression could increase the number of spontaneous contractions in the urinary bladder, and alter its reposne to physiological stretch. We aimed to: 1) study the patterns of TREK-1 expression in visceral organs (kidney, urinary bladder, and colon) in WT and TREK-1 KO mice, and 2) assess the role of TREK-1 channels in bladder contractility and voiding cycle. METHODS Adult C57BL/6J wild-type (WT, N=32) and TREK-1 KO (KO, N=33) mice were used in this study. We performed immunocytochemistry labeling, endpoint RT-PCR, detrusor muscle strip contractility studies, and awake cystometry to evaluate blader function. RESULTS No changes in visceral organ morphology or tissue histology were observed between WT and TREK-1 KO animals. Isometric contractility recordings from TREK-1 KO isolated detrusor strips showed elevated basal muscle tone and enhanced spontaneous activity in response to stretch (109% vs. 61% in WT group, p=0.05). Detrusor strips from TREK-1 KO mice also generated more contractile force in response to electric field and high potassium stimulation. Interestingly, cystometric recordings from TREK-1 KO mice revealed a significant increase in the duration of inter-micturition interval, also expressed enhanced bladder capacity and increased number of non-voiding contractions in comparison to WT mice. CONCLUSIONS Our data suggest that the knockout of TREK-1 channels has dual effects on detrusor contractility and micturition patterns, most likely due to expression of TREK-1 channels on both smooth muscle and neuronal cells. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e503-e504 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Ricardo Pineda More articles by this author Joseph Hypolite More articles by this author Sanghee Lee More articles by this author Alonso Carrasco More articles by this author Nao Iguchi More articles by this author Randall B Meacham More articles by this author Anna P Malykhina More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...