{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:40:36Z","timestamp":1772160036233,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T00:00:00Z","timestamp":1363046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Overactive bladder (\n OAB<\/jats:styled-content>\n ) is often associated with abnormally increased detrusor smooth muscle (\n DSM<\/jats:styled-content>\n ) contractions. We used\n NS309<\/jats:styled-content>\n , a selective and potent opener of the small or intermediate conductance\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n \u2010activated\n \n \n K\n +<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n (\n SK<\/jats:styled-content>\n or\n IK<\/jats:styled-content>\n , respectively) channels, to evaluate how\n SK<\/jats:styled-content>\n \/\n IK<\/jats:styled-content>\n channel activation modulates\n DSM<\/jats:styled-content>\n function.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n We employed single\u2010cell\n RT\u2010PCR<\/jats:styled-content>\n , immunocytochemistry, whole cell patch\u2010clamp in freshly isolated rat\n DSM<\/jats:styled-content>\n cells and isometric tension recordings of isolated\n DSM<\/jats:styled-content>\n strips to explore how the pharmacological activation of\n SK<\/jats:styled-content>\n \/\n IK<\/jats:styled-content>\n channels with\n NS309<\/jats:styled-content>\n modulates\n DSM<\/jats:styled-content>\n function.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n We detected\n SK3<\/jats:styled-content>\n but not\n SK1<\/jats:styled-content>\n ,\n SK2<\/jats:styled-content>\n or\n IK<\/jats:styled-content>\n channels expression at both\n mRNA<\/jats:styled-content>\n and protein levels by\n RT\u2010PCR<\/jats:styled-content>\n and immunocytochemistry in\n DSM<\/jats:styled-content>\n single cells.\n NS309<\/jats:styled-content>\n (10\u2009\n \u03bcM<\/jats:styled-content>\n ) significantly increased the whole cell\n SK<\/jats:styled-content>\n currents and hyperpolarized\n DSM<\/jats:styled-content>\n cell resting membrane potential. The\n NS309<\/jats:styled-content>\n hyperpolarizing effect was blocked by apamin, a selective\n SK<\/jats:styled-content>\n channel inhibitor.\n NS309<\/jats:styled-content>\n inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated\n DSM<\/jats:styled-content>\n strips in a concentration\u2010dependent manner. The inhibitory effect of\n NS309<\/jats:styled-content>\n on spontaneous phasic contractions was blocked by apamin but not by\n TRAM<\/jats:styled-content>\n \u201034, indicating no functional role of the\n IK<\/jats:styled-content>\n channels in rat\n DSM<\/jats:styled-content>\n .\n NS309<\/jats:styled-content>\n also significantly inhibited the pharmacologically and electrical field stimulation\u2010induced\n DSM<\/jats:styled-content>\n contractions.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n Our data reveal that\n SK3<\/jats:styled-content>\n channel is the main\n SK<\/jats:styled-content>\n \/\n IK<\/jats:styled-content>\n subtype in rat\n DSM<\/jats:styled-content>\n . Pharmacological activation of\n SK3<\/jats:styled-content>\n channels with\n NS309<\/jats:styled-content>\n decreases rat\n DSM<\/jats:styled-content>\n cell excitability and contractility, suggesting that\n SK3<\/jats:styled-content>\n channels might be potential therapeutic targets to control\n OAB<\/jats:styled-content>\n associated with detrusor overactivity.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.12049","type":"journal-article","created":{"date-parts":[[2012,11,12]],"date-time":"2012-11-12T16:31:38Z","timestamp":1352737898000},"page":"1611-1625","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["NS309<\/scp>\n decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating\n SK3<\/scp>\n channels"],"prefix":"10.1111","volume":"168","author":[{"given":"Shankar P","family":"Parajuli","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical & Biomedical Sciences South Carolina College of Pharmacy University of South Carolina Columbia SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiril L","family":"Hristov","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical & Biomedical Sciences South Carolina College of Pharmacy University of South Carolina Columbia SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupal P","family":"Soder","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical & Biomedical Sciences South Carolina College of Pharmacy University of South Carolina Columbia SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Whitney F","family":"Kellett","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical & Biomedical Sciences South Carolina College of Pharmacy University of South Carolina Columbia SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgi V","family":"Petkov","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical & Biomedical Sciences South Carolina College of Pharmacy University of South Carolina Columbia SC 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