Contribution of calcium-sensitive potassium channels to NS1619-induced relaxation in human pregnant myometrium

Large-conductance, calcium-sensitive potassium channels (BK(Ca)) are found at high density in the pregnant human myometrium. We have investigated, using isolated myometrial strips and freshly dispersed human myometrial cells, the action of a novel drug (NS1619) which has potassium channel opening activity. Isometric tension experiments demonstrated that NS1619 has a potent, relaxant effect on the pregnant human myometrium. Using both the inside-out and outside-out configurations of the patch-clamp technique, NS1619 appears to act directly on myometrial BK(Ca) channels to stimulate channel activity by increasing the time spent in the open state by this group of potassium channels. Consequently, the myometrial BK(Ca) channel may be a novel target site for drug intervention in clinical conditions, e.g. failure to labour, preterm labour or dysmenorrhoea, which may require either the augmentation or inhibition of uterine K+ channel activity.