Center for Womens Reproductive science Research

South Euclid, MO, United States

Center for Womens Reproductive science Research

South Euclid, MO, United States
SEARCH FILTERS
Time filter
Source Type

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.

Loading Center for Womens Reproductive science Research collaborators
Loading Center for Womens Reproductive science Research collaborators