{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:53:54Z","timestamp":1717721634530},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,12,22]],"date-time":"2011-12-22T00:00:00Z","timestamp":1324512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Aim:\u2002<\/jats:bold> To investigate the effect of 4,5\u2010dichloro\u20101,3\u2010diethyl\u20101,3\u2010dihydro\u2010benzoimidazol\u20102\u2010one (NS4591), a novel SK\/IK channels positive modulator, on human myometrial activity.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Organ bath studies were performed on myometrial preparations obtained from women undergoing elective caesarean section at term (<jats:italic>N<\/jats:italic>\u2003=\u200311) or hysterectomy (<jats:italic>N<\/jats:italic>\u2003=\u200311). NS4591 was added cumulatively in the concentration range of 0.3\u201330\u2003\u03bc<jats:sc>m<\/jats:sc>. In separate experiments, the effects of pre\u2010incubation of muscle preparation with the SK or IK channel blockers apamin (1\u2003\u03bc<jats:sc>m<\/jats:sc>) and TRAM34 (10\u2003\u03bc<jats:sc>m<\/jats:sc>) on the outcomes of NS4591 were evaluated. Simultaneous vehicle controls were performed for all experiments. The effects of drugs were studied on spontaneous contractions.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> NS4591 exerted an inhibitory effect on myometrial contractions in muscle strips from non\u2010pregnant and pregnant women. The contractility in non\u2010pregnant and pregnant myometrium was reduced to the following values respectively: amplitude 20.65\u2003\u00b1\u20037.38% (<jats:italic>P\u2003<\/jats:italic>&lt;<jats:italic>\u2003<\/jats:italic>0.001) and 42.85\u2003\u00b1 11.04% (<jats:italic>P\u2003<\/jats:italic>&lt;<jats:italic>\u2003<\/jats:italic>0.05) and area under the curve 11.72\u2003\u00b1\u20037.39% (<jats:italic>P\u2003<\/jats:italic>&lt;<jats:italic>\u2003<\/jats:italic>0.001) and 34.84\u2003\u00b1\u200310.50% (<jats:italic>P\u2003<\/jats:italic>&lt;<jats:italic>\u2003<\/jats:italic>0.001) and are reflective of 30\u2003\u03bc<jats:sc>m<\/jats:sc> NS4591 compared to vehicle control. In non\u2010pregnant tissue, apamin partially reduced the inhibitory effects of NS4591, but we observed relaxation mediated by NS4591 despite pre\u2010incubation with TRAM34. In contrast, in pregnant tissue, neither apamin nor TRAM34 could reverse the relaxatory effects of NS4591.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> Our findings imply that SK\/IK channels are present and functional in myometrium from pregnant and non\u2010pregnant women. The SK\/IK channel\u2010positive modulator NS4591 exerts relaxation of human myometrium <jats:italic>in vitro<\/jats:italic>, and this may have implications for the clinical management of preterm labour.<\/jats:p>","DOI":"10.1111\/j.1748-1716.2011.02384.x","type":"journal-article","created":{"date-parts":[[2011,11,18]],"date-time":"2011-11-18T17:52:30Z","timestamp":1321638750000},"page":"247-254","source":"Crossref","is-referenced-by-count":7,"title":["Relaxant effect of a novel calcium\u2010activated potassium channel modulator on human myometrial spontaneous contractility <i>in vitro<\/i>"],"prefix":"10.1111","volume":"205","author":[{"given":"S. T.","family":"Rosenbaum","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Larsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. C.","family":"Joergensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. 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