ArticleProceedings of the National Academy of Sciences of the United States of America2016
BKCa channel regulates calcium oscillations induced by alpha-2-macroglobulin in human myometrial smooth muscle cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Utero-placental calcium and magnesium ion channels: A systematic review of obstetric implications of their alterations.Channels (Austin, Tex.) · 2026Pooled it
- Smooth muscle of the lower urinary tract: BK-RyR coupling in physiology and pathophysiology.Journal of muscle research and cell motility · 2025Review
- SLO2.1/NALCN Functional Complex Activity in Mouse Myometrial Smooth Muscle Cells During Pregnancy.Journal of cellular physiology · 2025Article
- Small Molecule NS11021 Promotes BK Channel Activation by Increasing Inner Pore Hydration.Journal of chemical information and modeling · 2024Article
- Relaxin Modulates the Genomic Actions and Biological Effects of Estrogen in the Myometrium.Endocrinology · 2024Article
- Relaxin Modulates the Genomic Actions and Biological Effects of Estrogen in the Myometrium.bioRxiv : the preprint server for biology · 2024Article
- BKCa channels are involved in spontaneous and lipopolysaccharide-stimulated uterine contraction in late gestation mice†.Biology of reproduction · 2024Article
- Novel identification and modulation of the mechanosensitive Piezo1 channel in human myometrium.The Journal of physiology · 2023Article
- Article
- Moderate Ethanol-Preconditioning Offers Ischemic Tolerance Against Focal Cerebral Ischemic/Reperfusion: Role of Large Conductance Calcium-Activated Potassium Channel.Neurochemical research · 2022Article
- Uterine contractions in rodent models and humans.Acta physiologica (Oxford, England) · 2021Review
- The action of a BK channel opener.The Journal of general physiology · 2020Article
- Oxytocin can regulate myometrial smooth muscle excitability by inhibiting the NaThe Journal of physiology · 2019Article
- Maintenance of intracellular Ca2+ basal concentration in airway smooth muscle (Review).International journal of molecular medicine · 2018Review
- Cutting Edge: The Heat Shock Protein gp96 Activates Inflammasome-Signaling Platforms in APCs.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium.International journal of molecular sciences · 2018Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The large-conductance, voltage-gated, calcium (Ca(2+))-activated potassium channel (BKCa) plays an important role in regulating Ca(2+)signaling and is implicated in the maintenance of uterine quiescence during pregnancy. We used immunopurification and mass spectrometry to identify proteins that interact with BKCain myometrium samples from term pregnant (≥37 wk gestation) women. From this screen, we identified alpha-2-macroglobulin (α2M). We then used immunoprecipitation followed by immunoblot and the proximity ligation assay to confirm the interaction between BKCaand both α2M and its receptor, low-density lipoprotein receptor-related protein 1 (LRP1), in cultured primary human myometrial smooth muscle cells (hMSMCs). Single-channel electrophysiological recordings in the cell-attached configuration demonstrated that activated α2M (α2M*) increased the open probability of BKCain an oscillatory pattern in hMSMCs. Furthermore, α2M* caused intracellular levels of Ca(2+)to oscillate in oxytocin-primed hMSMCs. The initiation of oscillations required an interaction between α2M* and LRP1. By using Ca(2+)-free medium and inhibitors of various Ca(2+)signaling pathways, we demonstrated that the oscillations required entry of extracellular Ca(2+)through store-operated Ca(2+)channels. Finally, we found that the specific BKCablocker paxilline inhibited the oscillations, whereas the channel opener NS11021 increased the rate of these oscillations. These data demonstrate that α2M* and LRP1 modulate the BKCachannel in human myometrium and that BKCaand its immunomodulatory interacting partners regulate Ca(2+)dynamics in hMSMCs during pregnancy.
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Registered trials
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