Modulation of potassium current characteristics in human myometrial smooth muscle by 17beta-estradiol and progesterone.
The K(+) channel currents are important modulators of smooth muscle membrane potential and excitability. We assessed whether voltage-gated K(+) currents from human myometrium are regulated by placental steroid hormones during pregnancy and labor. Pregnant human myometrial cells were isolated from samples obtained at cesarean section. Primary cultured cells were treated with 100 nM 17beta-estradiol, 1 microM progesterone, or both hormones in combination for 24 h. Acute effects of the two hormones were also determined. The K(+) currents were recorded using the standard whole-cell, patch-clamp technique. Primary cultures possessed both delayed rectifier (I(KV)) and A-like (I(KA)) voltage-gated K(+) currents. The 24-h 17beta-estradiol treatment caused a hyperpolarizing shift in the steady-state inactivation of both I(KV) and I(KA). Progesterone treatment also shifted the inactivation of I(KA) and increased I(KV) amplitude by 60%-110%. Conversely, the combined treatment had no effect on these currents. Neither 17beta-estradiol (0.1-1 microM) nor progesterone (1-5 microM) had any effect on the K(+) current when applied acutely. These results show that 17beta-estradiol should inhibit myometrial K(+) channel activity, whereas progesterone is likely to have the opposite effect. These results are consistent with the respective procontractile and proquiescence roles for 17beta-estradiol and progesterone in human uterus during pregnancy.
Knock
G A
GA
The London Myometrium Group, Centre for Cardiovasular Biology and Medicine, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom. greg.knock@kcl.ac.uk
Tribe
R M
RM
Hassoni
A A
AA
Aaronson
P I
PI
D002478:Cells, Cultured; D002585:Cesarean Section; D004553:Electric Conductivity; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007743:Labor, Obstetric / Q000502:physiology; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*
D015221:Potassium Channels; D011374:Progesterone; D004958:Estradiol