Gestational change of K+ channel opener effect is correlated with the expression of uterine KATP channel subunits.
OBJECTIVE
We analyzed the gestational changes of pharmacological activity and molecular levels of KATP channels in rat myometrium.


METHODS
Using rat myometrium, the effects of K+ channel openers (KCOs) were examined in an isometric tension study of oxytocin-induced contraction. We also examined the effects of KCOs on the intracellular Ca2+ levels of cultured myometrial cells. The expression of myometrial KATP channels was assessed by RT-PCR and Northern blot analysis.


RESULTS
The effect of KCOs were altered during pregnancy, with a significant increase of their potency at day 18 of pregnancy followed by a decline towards the non-pregnant level at the day of delivery. KCOs suppressed the Ca2+ influx across the cell membrane. The mRNAs encoding each component of myometrial KATP channels, Kir6.1 and SUR2B, exhibited gestational stage-dependent alterations similar to those of the effects of KCOs.


CONCLUSIONS
These findings suggest that KCOs inhibit uterine myometrial contraction more effectively during pregnancy than in the non-pregnant state due to gestation-enhanced expression of KATP channels, implying that KCOs might be useful for preventing premature delivery.
Sawada
Kenjiro
K
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Morishige
Ken-ichirou
K
Hashimoto
Kae
K
Tasaka
Keiichi
K
Kurachi
Hirohisa
H
Murata
Yuji
Y
Kurachi
Yoshihisa
Y
D000818:Animals; D003981:Diazoxide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D010121:Oxytocin; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D012313:RNA / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014590:Uterine Contraction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D010121:Oxytocin; D012313:RNA; D003981:Diazoxide