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 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 x 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.
Shimano
M
M
Department of Obstetrics and Gynecology, Tokushima University, Tokushima, Japan. mishiman@mva.biglobe.ne.jp
Nakaya
Y
Y
Fukui
R
R
Kamada
M
M
Hamada
Y
Y
Maeda
K
K
Aono
T
T
D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009215:Myometrium / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011247:Pregnancy
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D015221:Potassium Channels; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D007548:Isosorbide Dinitrate; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester