{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T03:07:44Z","timestamp":1767841664932,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL085887"],"award-info":[{"award-number":["R01HL085887"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2P01HL066299"],"award-info":[{"award-number":["2P01HL066299"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S100D020149"],"award-info":[{"award-number":["S100D020149"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Uterine contractions prior to 37 weeks gestation can result in preterm labor with significant risk to the infant. Current tocolytic therapies aimed at suppressing premature uterine contractions are largely ineffective and cause serious side effects. Calcium (Ca2+) dependent contractions of uterine smooth muscle are physiologically limited by the opening of membrane potassium (K+) channels. Exploiting such inherent negative feedback mechanisms may offer new strategies to delay labor and reduce risk. Positive modulation of small conductance Ca2+-activated K+ (KCa2.3) channels with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA), effectively decreases uterine contractions. This study investigates whether the receptor agonist oxytocin might solicit KCa2.3 channel feedback that facilitates CyPPA suppression of uterine contractions. Using isometric force myography, we found that spontaneous phasic contractions of myometrial tissue from nonpregnant mice were suppressed by CyPPA and, in the presence of CyPPA, oxytocin failed to augment contractions. In tissues exposed to oxytocin, depletion of internal Ca2+ stores with cyclopiazonic acid (CPA) impaired CyPPA relaxation, whereas blockade of nonselective cation channels (NSCC) using gadolinium (Gd3+) had no significant effect. Immunofluorescence revealed close proximity of KCa2.3 channels and ER inositol trisphosphate receptors (IP3Rs) within myometrial smooth muscle cells. The findings suggest internal Ca2+ stores play a role in KCa2.3-dependent feedback control of uterine contraction and offer new insights for tocolytic therapies.<\/jats:p>","DOI":"10.3390\/ijms222413585","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"13585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Augmented KCa2.3 Channel Feedback Regulation of Oxytocin Stimulated Uterine Strips from Nonpregnant Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Megan","family":"Zak","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bri","family":"Kestler","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trudy","family":"Cornwell","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama College of Medicine, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.siny.2015.12.011","article-title":"The Epidemiology, Etiology, and Costs of Preterm Birth","volume":"21","author":"Frey","year":"2016","journal-title":"Semin. 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