{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:59:29Z","timestamp":1792673969725,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During filling, urinary bladder volume increases dramatically with little change in pressure. This is accomplished by suppressing contractions of the detrusor muscle that lines the bladder wall. Mechanisms responsible for regulating detrusor contraction during filling are poorly understood. Here we describe a novel pathway to stabilize detrusor excitability involving platelet-derived growth factor receptor-\u03b1 positive (PDGFR\u03b1<jats:sup>+<\/jats:sup>) interstitial cells. PDGFR\u03b1<jats:sup>+<\/jats:sup> cells express small conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup> (SK) and TRPV4 channels. We found that Ca<jats:sup>2+<\/jats:sup> entry through mechanosensitive TRPV4 channels during bladder filling stabilizes detrusor excitability. GSK1016790A (GSK), a TRPV4 channel agonist, activated a non-selective cation conductance that coupled to activation of SK channels. GSK induced hyperpolarization of PDGFR\u03b1<jats:sup>+<\/jats:sup> cells and decreased detrusor contractions. Contractions were also inhibited by activation of SK channels. Blockers of TRPV4 or SK channels inhibited currents activated by GSK and increased detrusor contractions. TRPV4 and SK channel blockers also increased contractions of intact bladders during filling. Similar enhancement of contractions occurred in bladders of <jats:italic>Trpv4<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice during filling. An SK channel activator (SKA-31) decreased contractions during filling, and rescued the overactivity of <jats:italic>Trpv4<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> bladders. Our findings demonstrate how Ca<jats:sup>2+<\/jats:sup> influx through TRPV4 channels can activate SK channels in PDGFR\u03b1<jats:sup>+<\/jats:sup> cells and prevent bladder overactivity during filling.<\/jats:p>","DOI":"10.1038\/s41598-017-12561-7","type":"journal-article","created":{"date-parts":[[2017,9,19]],"date-time":"2017-09-19T09:55:15Z","timestamp":1505814915000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Premature contractions of the bladder are suppressed by interactions between TRPV4 and SK3 channels in murine detrusor PDGFR\u03b1+ cells"],"prefix":"10.1038","volume":"7","author":[{"given":"Haeyeong","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung H.","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Peri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Corrigan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Tai","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita E.","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhupal P.","family":"Bhetwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeming","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Perrino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby C.","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenton M.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Don","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,25]]},"reference":[{"key":"12561_CR1","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/S0090-4295(03)00009-8","volume":"61","author":"TW Hu","year":"2003","unstructured":"Hu, T. 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