Knock G A, Tribe R M, Hassoni A A, Aaronson P I
The London Myometrium Group, Centre for Cardiovasular Biology and Medicine, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom.
Biol Reprod. 2001 May;64(5):1526-34. doi: 10.1095/biolreprod64.5.1526.
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.
钾离子通道电流是平滑肌膜电位和兴奋性的重要调节因子。我们评估了妊娠和分娩期间,人子宫肌层的电压门控钾离子电流是否受胎盘甾体激素调控。从剖宫产获取的样本中分离出妊娠人子宫肌层细胞。原代培养细胞用100 nM 17β-雌二醇、1 μM孕酮或两种激素联合处理24小时。还测定了这两种激素的急性效应。使用标准的全细胞膜片钳技术记录钾离子电流。原代培养细胞同时具有延迟整流钾电流(I(KV))和A样钾电流(I(KA))。17β-雌二醇处理24小时导致I(KV)和I(KA)的稳态失活均出现超极化偏移。孕酮处理也使I(KA)的失活发生偏移,并使I(KV)幅度增加60%-110%。相反,联合处理对这些电流没有影响。急性应用时,17β-雌二醇(0.1-1 μM)和孕酮(1-5 μM)对钾离子电流均无影响。这些结果表明,17β-雌二醇应抑制子宫肌层钾离子通道活性,而孕酮可能具有相反作用。这些结果与17β-雌二醇和孕酮在妊娠期间人子宫中各自的促收缩和促静息作用一致。