In vitro contractile response of rabbit myometrium to BK_Ca and K_ATP potassium channel openers.

摘要

The aim of the study was to evaluate the participation of ligand-sensitive potassium large conductance calcium-activated channels (BK_Ca) and ATP-sensitive potassium channels in uterine smooth muscle reactivity during different stages of the experimentally induced proliferatory and secretory phase in the sexual cycle in ovariectomized rabbits in vitro. The myometrial reactivity to oxytocin (10-6 mol/litre) was investigated by an in vitro method in female rabbits 14 days after ovariectomy treated with 17 beta -estradiol (1 mg/kg/day i.m. for seven days), or with a combination of progesterone 2 mg/kg/day s.c. for 7 days and 17 beta -estradiol (0.2 mg/kg/day (day 3-7)). The strips of myometrial smooth muscle were incubated with a specific opener (NS 1619) and an antagonist (TEA) of potassium large conductance calcium-activated channel, or with a specific opener (pinacidil) and an antagonist (glybenclamide) of ATP-sensitive potassium channels before the administration of oxytocin. NS1619 produced more potent inhibition of the oxytocin-induced contraction during the gestagen dominance (experimental secretory phase) than the one observed during the oestrogen dominance (experimental proliferatory phase). TEA antagonized the NS1619 induced inhibition of the myometrial contraction. In the matter of K_ATP potassium channels, after the administration of pinacidil we observed a similar situation in the changes of myometrial contractility. Pinacidil produced more pronounced inhibition of oxytocin-induced contraction during the secretory phase, and its effect was abolished by the selective inhibitor glybenclamide. Our experimental results indicate that both potassium large conductance calcium-activated channels and ATP-sensitive potassium channels significantly participate in the regulation of myometrial oxytocin-induced contractions and the activity of these channels is probably influenced by the levels of oestrogens and gestagens.