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Effect of NS11021, a novel BKCA channel opener, on non-pregnant and pregnant mouse myometrial contractility
  1. R Patel1,
  2. L A McCallum1,
  3. H Weidmann1,
  4. A Kadri1,
  5. I A Greenwood2,
  6. R M Tribe1
  1. 1Division of Women's Health, King's College London and King's Health Partners, London, UK
  2. 2Division of Biomedical Sciences, St George's University of London, London, UK

Abstract

Background It has been hypothesised that down-regulation of the potassium BKCa channel function at term is involved in myometrial activation at labour onset. However, there are conflicting reports on the contribution of this channel to uterine contractility. Our previous data suggests that BK channels do not modulate spontaneous contractility of human and rat myometrium in vitro. The BKCa activator NS1619, which can relax myometrial tissue, has been reported to mediate effects via ERG channels in other tissues. Our aim was to examine the effect of a more specific BKCa channel activator NS11021 versus NS1619 in non-pregnant and late pregnant mouse myometrium.

Methods Longitudinal myometrial strips obtained from non-pregnant (oestrous) and late pregnant (day 17–18) C57/BL6 mice were used for isometric tension recording; activity measured as mean integral tension. NS1619 (n=6–9), NS11021 (n=6–7) and its inactive analogue NS13558 (n=4–6) versus vehicle controls (n=3–12).

Results NS11021 (10 M) and NS13558 (10 M) had no effect on spontaneous myometrial contractions. NS1619 (10 M) had a small but non-significant effect on myometrial contractility from non-pregnant mice, but at 30 M concentrations induced a significant decrease in spontaneous contractility compared to vehicle control (260.5% vs 137.3%, p<0.05).

Conclusions NS11021 has no effect on spontaneous myometrial contractions from non-pregnant or late pregnant mice. The effect of NS1619, seen in this and previous studies, are more likely to have been mediated by an action of NS1619 on ERG channels.

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Footnotes

  • Funding Action Medical Research, (208701 & SC039284) Rosetrees Trust (298582), Tommy's (1060508) and British Pharmalogical Society.

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