Novel Expression and Regulation of Voltage-Dependent Potassium Channels in Placentas From Women With Preeclampsia
Open accessAbstract
Preeclampsia is associated with structural/functional alterations in placental and maternal vasculature. Voltage-dependant potassium channels encoded by KCNQ1-5 genes have been detected in several types of blood vessels where they promote vascular relaxation. Voltage-dependant potassium channel function can be modulated by KCNE1-5–encoded accessory proteins. The aim of this study was to determine whether KCNQ and KCNE genes are differentially expressed in placentas from women with preeclampsia compared with normotensive controls and to examine any differences in those who delivered preterm (<37 weeks) or term. Placental biopsies (from midway between the cord and periphery) were obtained, with consent, from white European control (n=24; term) and preeclamptic (n=22; of whom 8 delivered before 37 weeks' gestation) women. KCNQ/KCNE and GAPDH mRNA expressions were determined by quantitative RT-PCR. Protein expression/localization was assessed using immunohistochemistry. KCNQ3 and KCNE5 mRNA expressions were significantly upregulated in preeclampsia (median [interquartile range]: 1.942 [0.905 to 3.379]) versus controls (0.159 [0.088 to 0.288];P=0.001) and exhibited a strong positive correlation with each other (P<0.001), suggesting a novel heterodimer. Enhanced protein expression of KCNQ3 and KCNE5 in preeclampsia was confirmed with localization mainly restricted to the syncytiotrophoblast. KCNQ4 and KCNE1 isoforms were suppressed in placentas from term preeclamptic women versus controls (P≤0.05). KCNQ1 mRNA expression was increased and KCNQ5 decreased in the preterm preeclamptic group versus controls (P<0.05). In summary, voltage-dependant potassium channels are expressed and markedly modulated in placentas from preeclamptic women. Differential expression of isoforms may lead to altered cell proliferation. The correlation between KCNQ3 and KCNE5 expression is indicative of a novel channel complex and warrants further investigation.
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Voltage-dependent K+ channels have been immunolocalized to the syncytiotrophoblast, cytotrophoblast and some stromal cells in the first trimester and term placenta.
“Voltage-dependent K + channels have also been immunolocalized to the syncytiotrophoblast, cytotrophoblast and some stromal cells in the first trimester and term placenta (382, 383), and so they may play a broader role in placental biology, including regulating the secretion of hCG (574).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [383]
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Placental Origins of Chronic Disease
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Self-citation
- Authors
- Mistry, H. D., McCallum, L. A., Kurlak, L. O., Greenwood, I. A., Broughton Pipkin, F., & Tribe, R. M.
- Affiliations
- University of Nottingham (GB)
- From the Division of Women's Health (H.D.M., L.A.M., R.M.T.), King's College London and King's Health Partners, London, United Kingdom; Department of Obstetrics and Gynaecology (L.O.K., F.B.P.), University of Nottingham, Nottingham, United Kingdom; Basic Medical Sciences (I.A.G.), St George's University of London, London, United Kingdom.
- Venue
- Hypertension
- Published
- 2011-09
- Volume
- 58
- Issue
- 3
- Pages
- 497-504
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2162414431
- Cited by
- 48
- References
- 43
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 6 · 2015: 4 · 2014: 1 · 2013: 5 · 2012: 2
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- other-oa
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (acceptedVersion, other-oa)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Nottingham ePrints (University of Nottingham) (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Action Medical Research
- Rosetrees Trust
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
- Keywords
- preeclampsia, voltage-gated potassium channels, KCNQ3, KCNE5, KCNQ4, KCNE1, KCNQ1, KCNQ5, placenta, syncytiotrophoblast, preterm birth, gene expression, vasorelaxation
- MeSH terms
- Adult, Female, Humans, Immunohistochemistry, Infant, Newborn, Infant, Premature, Placenta, Pre-Eclampsia, Pregnancy, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Potassium Channels, Voltage-Gated, White People, KCNQ Potassium Channels, KCNQ1 Potassium Channel, KCNQ3 Potassium Channel, Young Adult
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