Relaxant effect of a novel calcium-activated potassium channel modulator on human myometrial spontaneous contractility in vitro.

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 μ m. In separate experiments, the effects of pre-incubation of muscle preparation with the SK or IK channel blockers apamin (1 μ m) and TRAM34 (10 μ m) 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 μ m 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. [ABSTRACT FROM AUTHOR]