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Endocrinology. 2014 Aug;155(8):3112-22. doi: 10.1210/en.2014-1152. Epub 2014 Jun 10.

BK channels regulate myometrial contraction by modulating nuclear translocation of NF-κB.

Author information

1
Center for Women's Reproductive Sciences Research, Department of Obstetrics and Gynecology, Basic Science Division, Washington University in St Louis, St Louis, Missouri 63110.

Abstract

The large-conductance Ca(2+)-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 nuclear factor-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-κB translocation into the nucleus. We compared the effects of BK channel modulation to those of LPS on NF-κB 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-κB 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 Ca(2+)-activated K(+) channel protein 3 had an effect on NF-κB 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.

PMID:
24914944
PMCID:
PMC4098006
DOI:
10.1210/en.2014-1152
[Indexed for MEDLINE]
Free PMC Article

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