BK Channels Regulate Myometrial Contraction by Modulating Nuclear Translocation of NF-κB

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.

Quercetin‐3‐methyl ether inhibits esophageal carcinogenesis by targeting the AKT/mTOR/p70S6K and MAPK pathways

“…Evidence indicates that almost 20% of human cancers are associated with chronic inflammation . Nuclear factor kappa B (NF‐κB) represents a family of important regulators involved in immune and inflammatory responses by activating transcription of a number of target genes . One target gene of activated NF‐κB is cyclooxygenase‐2 ( cox‐2 ), a key enzyme in the biosynthesis of prostaglandins, which can promote cancer progression by mediating signaling pathways governing cell proliferation, migration, and apoptosis .…”

Further studies of ion channels in the electroreceptor of the skate through deep sequencing, cloning and cross species comparisons

“…Thus the results in Table 1 are not inconsistent with existing knowledge. A complicating factor is that a substantial proportion of Kcnma1 molecules reside in intracellular compartments including the mitochon-dria [33], nuclear envelope [34] and sometimes the nucleoplasm. Further studies are needed to investigate the localization of Kcnma1 transcripts in the ampulla of Lorenzini and the role of beta subunits.…”

“…BK channels are known to be present in mitochondria, and BK channels in mitochondria have a specific insert at alternative splice site 7 which controls targeting [33 ]. More recently, Li et al [34 ] have reported that BK channels are present in the nuclear envelope of hippocampal neurons, where they regulate membrane potential and modulate release of calcium into the nucleoplasm, which leads to expression of specific genes.…”

Expression of Potassium Channels in Uterine Smooth Muscle Cells from Patients with Adenomyosis

“…BKCa channels mediate uterine relaxation by modulating nuclear translocation of nuclear factor kappa B. [ 13 ] In animal models, BKCa channels contribute approximately 35% of the total myocyte repolarizing K + currents in the nonpregnant state.…”