You have accessJournal of UrologyLate-Breaking S&T Poster1 Apr 2016LB-S&T-37 INTERACTION OF TRPV4 AND SK3 CHANNELS IN DETRUSOR PDGFR?+ CELLS CONTROLS BLADDER FILLING Haeyeong Lee, Byoung Koh, Robert Corrigan, Lauren Peri, Brian Perrino, Toby Chai, Kenton Sanders, and Sang Don Koh Haeyeong LeeHaeyeong Lee More articles by this author , Byoung KohByoung Koh More articles by this author , Robert CorriganRobert Corrigan More articles by this author , Lauren PeriLauren Peri More articles by this author , Brian PerrinoBrian Perrino More articles by this author , Toby ChaiToby Chai More articles by this author , Kenton SandersKenton Sanders More articles by this author , and Sang Don KohSang Don Koh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.03.118AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recently we reported the functional expression of SK channels in detrusor PDGFRa+ cells. This cell does not display voltage dependent Ca2+ channels. Finding the source of extracellular Ca2+ influx is critical for activation of SK channels. TRPV are relatively more Ca2+ permeable. In previous papers, TRPV4 KO mice demonstrated an increase in frequency of non voiding contractions (NVCs). The mechanism of this phenotype has not been studied. Thus, we hypothesized that TRPV4 channels are main source of Ca2+ influx to activate SK channels during filling. METHODS We applied molecular approaches, protein chemistry, patch clamp techniques, isometric force measurement, ex vivo cystometry, Ca2+ imaging techniques. PDGFRa/eGFP and C57BL/6 mice were used for cell sorting and patch clamp. Molecular expression of Trp channels and protein protein interaction between TRPV4 and SK3 channels were examined. Effects of TRPV4 agonist and antagonist were also examined on PDGFRa+ cells and smooth muscle cells (SMC) using patch clamp approaches. Detrusor contractility, ex vivo cystometry and Ca2+ imaging analysis were employed for functional analysis. RESULTS Quantitative analysis of transcripts demonstrated that Trpv4 is highly expressed in murine PDGFRa+ cells. In patch clamp experiments a TRPV4 channel agonist, GSK1016790A (GSK), activated TRPV4 current that was linked to activation of SK current. Under current clamp, GSK induced membrane hyperpolarization of detrusor PDGFRa+ cells. GSK activated SK currents were blocked by TRPV4 antagonists. Detrusor SMCs were unresponsive to GSK. In contractile experiments, GSK decreased phasic contractions in a dose dependent manner. TRPV4 antagonist increased phasic contractions. In ex vivo cystometry, GSK increased non-voiding contractions in the presence of apamin. In contrast TRPV4 antagonist increased NVCs, and NVCs were also elevated significantly in bladders of Trpv4 KO mice. Proximity ligation assays demonstrated protein protein interactions between TRPV4 and SK3 channels. GSK increased Ca2+ transients only in PDGFRa+ cells but not in SMC. CONCLUSIONS TRPV4 and SK channels are functionally interacted closely in plasma membrane of PDGFRa+ cells. Ca2+ influx through TRPV4 channels directly activates SK channels. Since TRPV4 are mechanosensitive channels, activation of TRPV4 during bladder filling stabilize membrane potentials and prevent detrusor overactivity. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e352 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Haeyeong Lee More articles by this author Byoung Koh More articles by this author Robert Corrigan More articles by this author Lauren Peri More articles by this author Brian Perrino More articles by this author Toby Chai More articles by this author Kenton Sanders More articles by this author Sang Don Koh More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...