Modulation of potassium current characteristics in human myometrial smoothmuscle by 17 beta-estradiol and progesterone

The K+ channel currents are important modulators of smooth muscle membrane potential and excitability. We assessed whether voltage-gated K+ currents f rom human myometrium are regulated by placental steroid hormones during pre gnancy and labor. Pregnant human myometrial cells were isolated from sample s obtained at cesarean section. Primary cultured cells were treated with 10 0 nM 17 beta -estradiol, 1 muM progesterone, or both hormones in combinatio n for 24 h. Acute effects of the two hormones were also determined. The Kcurrents were recorded using the standard whole-cell, patch-clamp technique . Primary cultures possessed both delayed rectifier (I,,) and A-like (I,) v oltage-gated K+ currents. The 24-h 17 beta -estradiol treatment caused a hy perpolarizing shift in the steady-state inactivation of both I, and I,. Pro gesterone treatment also shifted the inactivation of I, and increased I,, a mplitude by 60%-110%. Conversely, the combined treatment had no effect on t hese currents. Neither 17 beta -estradiol (0.1-1 muM) nor progesterone (1-5 muM) had any effect on the K+ current when applied acutely. These results show that 17 beta -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 prequiescence roles f or 17 beta -estradiol and progesterone in human uterus during pregnancy.