1. Activation of Ca2+-Activated K+ Channels in Human Myometrium by Nitric Oxide
- Author
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Miho Shimano, Toshihiro Aono, Masaharu Kamada, Rijin Fukui, Kazuhisa Maeda, Yoko Hamada, and Yutaka Nakaya
- Subjects
medicine.medical_specialty ,biology ,Arginine ,Chemistry ,Myometrium ,Obstetrics and Gynecology ,chemistry.chemical_element ,Calcium ,Potassium channel ,Nitric oxide ,Nitric oxide synthase ,chemistry.chemical_compound ,Endocrinology ,Reproductive Medicine ,Internal medicine ,medicine ,biology.protein ,Patch clamp ,Intracellular - Abstract
To investigate the mechanism of human uterine smooth muscle relaxation, the activation of Ca2+-activated K+ channels in cultured myometrial cells obtained from human pregnant myometrium at term by nitric oxide was evaluated at the single cell level using the patch-clamp technique. The open probability of the K+ channel after the addition of 3 × 10–3 M isosorbide dinitrate, a nitric oxide donor (0.116 ± 0.048) was significantly higher than that before the addition (0.059 ± 0.032; n = 9, p < 0.01). In myometrial cells pretreated with lipopolysaccharide, activation of K+ channels was also noted 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 probability 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 nitric oxide synthase, or 10–6 M methylene blue, an inhibitor of guanylate cyclase, abolished activation of the K+ channel by 10–3 M L-arginine in pretreated myometrial cells with lipopolysaccharide. Application of 10–3 M L-arginine to the intracellular surface of an excised inside-out patch in the myometrial cells pretreated with lipopolysaccharide failed to increase Ca2+-activated K+ channel activity, suggesting that the activation was mediated by intracellular messengers. These results indicate that nitric oxide should control human myometrial relaxation during pregnancy via activation of Ca2+-activated K+ channels.
- Published
- 2000
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