title: Novel expression and regulation of voltage-dependent potassium channels in placentas from women with preeclampsia.
abstract: 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.
authors: Maternal and Fetal Research Unit, Division of Women's Health, King's College London, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK. hiten.mistry@kcl.ac.uk
authors: Hiten D
authors: HD
authors: Mistry
authors: Laura A
authors: LA
authors: McCallum
authors: Lesia O
authors: LO
authors: Kurlak
authors: Iain A
authors: IA
authors: Greenwood
authors: Fiona
authors: F
authors: Broughton Pipkin
authors: Rachel M
authors: RM
authors: Tribe
mesh_terms: D000328:Adult; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007234:Infant, Premature; D051656:KCNQ Potassium Channels / Q000235:genetics / Q000378:metabolism; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C489622:KCNE1 protein, human; C502068:KCNE5 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; C117367:KCNQ4 protein, human; C412231:KCNQ5 protein, human; D024642:Potassium Channels, Voltage-Gated