Relaxant effect of a novel calcium-activated potassium channel modulator on human myometrial spontaneous contractility in vitro S. T. Rosenbaum, 1,2 T. Larsen, 1 J. C. Joergensen 1 and P. N. Bouchelouche 2 1 Department of Gynecology and Obstetrics, Holbaek Hospital, Holbaek, Denmark 2 Smooth Muscle Research Center, Department of Clinical Biochemistry, Koege Hospital, Koege, Denmark Received 6 July 2011, revision requested 5 August 2011, final revision received 7 November 2011, accepted 14 November 2011 Correspondence: S. T. Rosenbaum, Department of Gynecology and Obstetrics, Holbaek Hospital, Smedelundsgade 60, 4300 Holbaek, Denmark. E-mail: stre@regionsjaelland.dk Abstract 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 lm. In separate experiments, the effects of pre-incubation of muscle preparation with the SK or IK channel blockers apamin (1 lm) and TRAM34 (10 lm) 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 val- ues respectively: amplitude 20.65 Æ 7.38% (P < 0.001) and 42.85 Æ 11.04% (P < 0.05) and area under the curve 11.72 Æ 7.39% (P < 0.001) and 34.84 Æ 10.50% (P < 0.001) and are reflective of 30 lm NS4591 compared to vehicle control. In non-pregnant tissue, apamin partially re- duced 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 func- tional 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. Keywords human myometrium, NS4591, preterm birth, SK channels, tocolysis. Preterm birth (<37 weeks of gestation) accounts for 9.6% of all births worldwide (Beck et al. 2010). In addition, perinatal mortality because of preterm birth accounts for 28% of all neonatal deaths globally (Lawn et al. 2005). Tocolytic agents currently employed clinically (oxy- tocin receptor antagonists, b2 adrenoceptor agonists and calcium channel blockers) have not shown amelio- ration in the perinatal or neonatal outcomes and have adverse effects on women in preterm labour (Gyetvai Acta Physiol 2012, 205, 247–254 Ó 2011 The Authors Acta Physiologica Ó 2011 Scandinavian Physiological Society, doi: 10.1111/j.1748-1716.2011.02384.x 247