{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:57:11Z","timestamp":1762865831442},"reference-count":39,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p> Organized uterine contractions, including those necessary for parturition, are dependent on calcium entry through voltage-gated calcium channels in myometrial smooth muscle cells. Recent evidence suggests that small-conductance Ca<jats:sup>2+<\/jats:sup>-activated potassium channels (K<jats:sub>Ca<\/jats:sub>2), specifically isoforms K<jats:sub>Ca<\/jats:sub>2.2 and 2.3, may control these contractions through negative feedback regulation of Ca<jats:sup>2+<\/jats:sup> entry. We tested whether selective pharmacologic activation of K<jats:sub>Ca<\/jats:sub>2.2\/2.3 channels might depress uterine contractions, providing a new strategy for preterm labor intervention. Western blot analysis and immunofluorescence microscopy revealed expression of both K<jats:sub>Ca<\/jats:sub>2.2 and K<jats:sub>Ca<\/jats:sub>2.3 in the myometrium of nonpregnant (NP) and pregnant (gestation day 10 and 16; D10 and D16, respectively) mice. Spontaneous phasic contractions of isolated NP, D10, and D16 uterine strips were all suppressed by the K<jats:sub>Ca<\/jats:sub>2.2\/2.3-selective activator CyPPA in a concentration-dependent manner. This effect was antagonized by the selective K<jats:sub>Ca<\/jats:sub>2 inhibitor apamin. Whereas CyPPA sensitivity was reduced in D10 and D16 versus NP strips (pIC<jats:sub>50<\/jats:sub> 5.33 \u00b1 0.09, 4.64 \u00b1 0.03, 4.72 \u00b1 0.10, respectively), all contractions were abolished between 30 and 60 \u03bcM. Blunted contractions were associated with CyPPA depression of spontaneous Ca<jats:sup>2+<\/jats:sup> events in myometrial smooth muscle bundles. Augmentation of uterine contractions with oxytocin or prostaglandin F<jats:sub>2\u03b1<\/jats:sub> did not reduce CyPPA sensitivity or efficacy. Finally, in an RU486-induced preterm labor model, CyPPA significantly delayed time to delivery by 3.4 h and caused a 2.5-fold increase in pup retention. These data indicate that pharmacologic stimulation of myometrial K<jats:sub>Ca<\/jats:sub>2.2\/2.3 channels effectively suppresses Ca<jats:sup>2+<\/jats:sup>-mediated uterine contractions and delays preterm birth in mice, supporting the potential utility of this approach in tocolytic therapies. <\/jats:p>","DOI":"10.1152\/ajpcell.00082.2011","type":"journal-article","created":{"date-parts":[[2011,7,28]],"date-time":"2011-07-28T04:13:00Z","timestamp":1311826380000},"page":"C1027-C1035","source":"Crossref","is-referenced-by-count":11,"title":["CyPPA, a positive modulator of small-conductance Ca<sup>2+<\/sup>-activated K<sup>+<\/sup> channels, inhibits phasic uterine contractions and delays preterm birth in mice"],"prefix":"10.1152","volume":"301","author":[{"given":"Dana V.","family":"Skarra","sequence":"first","affiliation":[{"name":"Department of Physiology, University of South Alabama College of Medicine, Mobile, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trudy","family":"Cornwell","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of South Alabama College of Medicine, Mobile, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktoriya","family":"Solodushko","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of South Alabama College of Medicine, Mobile, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of South Alabama College of Medicine, Mobile, Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of South Alabama College of Medicine, Mobile, 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