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South Euclid, MO, United States

Li Y.,Center for Womens Reproductive science Research | Lorca R.A.,Center for Womens Reproductive science Research | Ma X.,Center for Womens Reproductive science Research | Rhodes A.,Center for Womens Reproductive science Research | England S.K.,Center for Womens Reproductive science Research
Endocrinology | Year: 2014

The large-conductance Ca2+-activated K+ (BK) channel plays an essential role in maintaining uterine quiescence during pregnancy. Growing evidence has shown a link between the BK channel and bacterial lipopolysaccharide (LPS)-induced nuclearfactor-κB (NF-κB) activation in macrophages. In the uterus, NF-κB activation plays an important role in inflammatory processes that lead to parturition. Our objective was to determine whether the BK channel regulates uterine contraction, in part, by modulating NF-KB translocation into the nucleus. We compared the effects of BK channel modulation to those of LPS on NF-KB nuclear translocation and contraction in an immortalized human myometrial cell line (human telomerase reverse transcriptase [hTERT]) and uterine myocytes. Our results showed that BK channel inhibitors paxilline and penitrem A induced translocation of NF-KB into the nucleus in both hTERT cells and uterine myocytes to a similar extent as LPS treatment, and LPS and paxilline similarly reduced BK channel currents. Conversely, neither BK channel openers nor blockade of the small conductance Ca2+-activated K+ channel protein 3 had an effect on NF-KB translocation. Additionally, collagen-based assays showed that paxilline induced contraction of hTERT cells and uterine myocytes. This was dependent upon cyclooxygenase-2 activity. Moreover, paxilline-induced contractility and increased cyclooxygenase-2 expression both depended on availability of free NF-κB. This study suggests that BK channels regulate myometrial contraction, in part, by modulating nuclear translocation of NF-κB. Copyright © 2014 by the Endocrine Society. Source

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