Activation of Ca2+-activated K+ channels in human myometrium by nitric oxide

To investigate the mechanism of human uterine smooth muscle relaxation, the activation of Ca2+-activated K+ channels in cultured myometrial cells obta ined from human pregnant myometrium at term by nitric oxide was evaluated a t the single cell level using the patch-clamp technique. The open probabili ty of the K+ channel after the addition of 3 x 10(-3) M isosorbide dinitrat e, a nitric oxide donor (0.116 +/- 0.048) was significantly higher than tha t before the addition (0.059 +/- 0.032; n = 9, p < 0.01). In myometrial cel ls pretreated with lipopolysaccharide, activation of K+ channels was also n oted after the addition of L-arginine (10(-4) M; open probability increased from 0.179 +/- 0.076 to 0.380 +/- 0.105, n = 9, p < 0.01: 10(-3) M; open p robability increased from 0.073 +/- 0.050 to 0.242 +/- 0.098, n = 12, p < 0 .01). Either 10(-3) M N-nitro-L-arginine-methyl-ester, an inhibitor of nitr ic oxide synthase, or 10(-6) M methylene blue, an inhibitor of guanylate cy clase, abolished activation of the K+ channel by 10(-3) M L-arginine in pre treated myometrial cells with lipopolysaccharide. Application of 10(-3) M L -arginine to the intracellular surface of an excised inside-out patch in th e myometrial cells pretreated with lipopolysaccharide failed to increase Ca 2+-activated K+ channel activity, suggesting that the activation was mediat ed by intracellular messengers. These results indicate that nitric oxide sh ould control human myometrial relaxation during pregnancy via activation of Ca2+-activated K+ channels. Copyright (C) 2000 S. Karger AG, Basel.