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Expression and function of Kv7 channels in murine myometrium throughout oestrous cycle

  • Molecular and Genomic Physiology
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Abstract

This study represents an extensive characterisation of the expression and functional impact of KCNQ and KCNE accessory subunits in a murine uterus using a combination of quantitative reverse transcription polymerase chain reaction, Western blot analysis, patch clamp electrophysiology and isometric tension recording. The use of uterine tissue throughout the oestrous cycle provided a physiological model with which to assess hormonal regulation of these genes. Messenger ribonucleic acid for all KCNQ genes were detected throughout the oestrous cycle with the KCNQ1 message predominant. KCNE isoforms were detected at each stage of the cycle. KCNE4 was the most abundant (p < 0.0001), and KCNQ1, KCNQ5 and KCNE1 were up-regulated in metestrous (p < 0.0001). The Kv7 channel inhibitor XE991 reduced outward K+ currents and significantly increased spontaneous myometrial contractions (p < 0.05), whereas retigabine (Kv7 activator) significantly relaxed uterine tissues (p < 0.001). These data are the first to characterise KCNQ and KCNE gene expression in a cell type outside of neurons and the cardiovascular system.

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Acknowledgements

The authors thank Dr. M Schwake (University of Kiel), Dr. Ohya (Nagoya City University) and Dr. S Yeung (St George’s, London) for their help with the initial primer design, Dr. W Sones (St. George’s) for help with the electrophysiology, Lawrence Murphy (Corbett Research) and Dr. David Sugden for their technical advice and support regarding real-time RT-PCR and The BSU at St. Thomas’ Hospital for their assistance and support with animal handling. This study was funded by Tommy’s the Baby Charity (registered charity no. 1060508) and KCL School of Medicine.

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Authors and Affiliations

  1. Maternal and Fetal Research Unit, Division of Reproduction and Endocrinology, King’s College London, St Thomas’ Hospital Campus, London, UK

    Laura A. McCallum & Rachel M. Tribe

  2. Division of Basic Medical Sciences, Ion Channels and Cell Signalling Research Centre, St. George’s University of London, London, UK

    Iain A. Greenwood

  3. Maternal and Fetal Research Unit, Department of Women’s Health, 10th Floor, North Wing, St. Thomas’ Hospital, Lambeth Palace Road, London, SE1 7EH, UK

    Laura A. McCallum

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  1. Laura A. McCallum
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  2. Iain A. Greenwood
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  3. Rachel M. Tribe
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Correspondence to Laura A. McCallum.

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McCallum, L.A., Greenwood, I.A. & Tribe, R.M. Expression and function of Kv7 channels in murine myometrium throughout oestrous cycle. Pflugers Arch - Eur J Physiol 457, 1111–1120 (2009). https://doi.org/10.1007/s00424-008-0567-5

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  • DOI: https://doi.org/10.1007/s00424-008-0567-5

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