Relaxant effect of a novel calcium-activated potassium channel modulator on human myometrial spontaneous contractility in vitro
Article first published online: 22 DEC 2011
© 2011 The Authors Acta Physiologica © 2011 Scandinavian Physiological Society
Volume 205, Issue 2, pages 247–254, June 2012
How to Cite
Rosenbaum, S. T., Larsen, T., Joergensen, J. C. and Bouchelouche, P. N. (2012), Relaxant effect of a novel calcium-activated potassium channel modulator on human myometrial spontaneous contractility in vitro. Acta Physiologica, 205: 247–254. doi: 10.1111/j.1748-1716.2011.02384.x
- Issue published online: 23 APR 2012
- Article first published online: 22 DEC 2011
- Accepted manuscript online: 18 NOV 2011 12:51PM EST
- Received 6 July 2011, revision requested 5 August 2011, final revision received 7 November 2011, accepted 14 November 2011
- human myometrium;
- preterm birth;
- SK channels;
Aim: To investigate the effect of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a novel SK/IK channels positive modulator, on human myometrial activity.
Methods: Organ bath studies were performed on myometrial preparations obtained from women undergoing elective caesarean section at term (N = 11) or hysterectomy (N = 11). NS4591 was added cumulatively in the concentration range of 0.3–30 μm. In separate experiments, the effects of pre-incubation of muscle preparation with the SK or IK channel blockers apamin (1 μm) and TRAM34 (10 μm) on the outcomes of NS4591 were evaluated. Simultaneous vehicle controls were performed for all experiments. The effects of drugs were studied on spontaneous contractions.
Results: NS4591 exerted an inhibitory effect on myometrial contractions in muscle strips from non-pregnant and pregnant women. The contractility in non-pregnant and pregnant myometrium was reduced to the following values respectively: amplitude 20.65 ± 7.38% (P < 0.001) and 42.85 ± 11.04% (P < 0.05) and area under the curve 11.72 ± 7.39% (P < 0.001) and 34.84 ± 10.50% (P < 0.001) and are reflective of 30 μm NS4591 compared to vehicle control. In non-pregnant tissue, apamin partially reduced the inhibitory effects of NS4591, but we observed relaxation mediated by NS4591 despite pre-incubation with TRAM34. In contrast, in pregnant tissue, neither apamin nor TRAM34 could reverse the relaxatory effects of NS4591.
Conclusion: Our findings imply that SK/IK channels are present and functional in myometrium from pregnant and non-pregnant women. The SK/IK channel-positive modulator NS4591 exerts relaxation of human myometrium in vitro, and this may have implications for the clinical management of preterm labour.