Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

The contribution of Kv7 channels to pregnant mouse and human myometrial contractility.

McCallum, LA; Pierce, SL; England, SK; Greenwood, IA; Tribe, RM (2011) The contribution of Kv7 channels to pregnant mouse and human myometrial contractility. Journal of Cellular and Molecular Medicine, 15 (3). pp. 577-586. ISSN 1582-4934
SGUL Authors: Greenwood, Iain Andrew

PDF Published Version
Download (722kB) | Preview


Premature birth accounts for approximately 75% of neonatal mortality and morbidity in the developed world. Despite this, methods for identifying and treating women at risk of preterm labour are limited and many women still present in preterm labour requiring tocolytic therapy to suppress uterine contractility. The aim of this study was to assess the utility of Kv7 channel activators as potential uterine smooth muscle (myometrium) relaxants in tissues from pregnant mice and women. Myometrium was obtained from early and late pregnant mice and from lipopolysaccharide (LPS)-injected mice (day 15 of gestation; model of infection in pregnancy). Human myometrium was obtained at the time of Caesarean section from women at term (38-41 weeks). RT-PCR/qRT-PCR detected KCNQ and KCNE expression in mouse and human myometrium. In mice, there was a global suppression of all KCNQ isoforms, except KCNQ3, in early pregnancy (n= 6, P < 0.001 versus late pregnant); expression subsequently increased in late pregnancy (n= 6). KCNE isoforms were also gestationally regulated (P < 0.05). KCNQ and KCNE isoform expression was slightly down-regulated in myometrium from LPS-treated-mice versus controls (P < 0.05, n= 3-4). XE991 (10 μM, Kv7 inhibitor) significantly increased spontaneous myometrial contractions in vitro in both human and mouse myometrial tissues (P < 0.05) and retigabine/flupirtine (20 μM, Kv7 channel activators) caused profound myometrial relaxation (P < 0.05). In summary, Kv7 activators suppressed myometrial contraction and KCNQ gene expression was sustained throughout gestation, particularly at term. Consequently, activation of the encoded channels represents a novel mechanism for treatment of preterm labour.

Item Type: Article
Additional Information: © 2011 The Authors Journal of Cellular and Molecular Medicine. © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.Open Access. The published version made available here with permission from the publisher.
Keywords: Aminopyridines, Animals, Anthracenes, Anticonvulsants, Carbamates, Female, Gene Expression, Gestational Age, Humans, KCNQ Potassium Channels, Lipopolysaccharides, Mice, Mice, Inbred C57BL, Myometrium, Phenylenediamines, Potassium Channel Blockers, Potassium Channels, Voltage-Gated, Pregnancy, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Uterine Contraction, potassium channel, uterus, preterm labour, KCNQ, KCNE, Science & Technology, Life Sciences & Biomedicine, Cell Biology, Medicine, Research & Experimental, Research & Experimental Medicine, CELL BIOLOGY, MEDICINE, RESEARCH & EXPERIMENTAL, POTASSIUM CHANNELS, K+ CHANNELS, ACTIVATION KINETICS, PRETERM LABOR, EXPRESSION, SUBUNITS, KCNE2, RETIGABINE, MUSCLE, ONSET, Biochemistry & Molecular Biology, 0304 Medicinal And Biomolecular Chemistry, 0601 Biochemistry And Cell Biology, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
Language: eng
March 2011Published
Project IDFunderFunder ID
PubMed ID: 20132415
Web of Science ID: WOS:000288798000012
Go to PubMed abstract
Publisher's version:

Actions (login required)

Edit Item Edit Item