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Modulation of Potassium Current Characteristics in Human Myometrial Smooth Muscle by 17ß-Estradiol and Progesterone¹

^a The London Myometrium Group, Centre for Cardiovasular Biology and Medicine, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom ^b Fetal Health Research Group, Division of Obstetrics and Gynaecology, St. Thomas' Campus, London SE1 7EH, United Kingdom ^c Guy's, King's, and St. Thomas' Schools of Biomedical Sciences and Medicine, London SE1 1UL, United Kingdom

ABSTRACT

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 17ß-estradiol, 1 µM 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 17ß-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 17ß-estradiol (0.1–1 µM) nor progesterone (1–5 µM) had any effect on the K⁺ current when applied acutely. These results show that 17ß-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 17ß-estradiol and progesterone in human uterus during pregnancy.

FOOTNOTES

First decision: 17 October 2000.

¹ Supported by the Tommy's Campaign, registered charity 1060508.

² Correspondence: Greg A. Knock, Centre for Cardiovasular Biology and Medicine, Room 2.30, New Hunt's House, Guy's, King's, and St. Thomas' Schools of Biomedical Sciences and Medicine, Guy's Campus, London SE1 1UL, UK. FAX: 44 207 848 6371; greg.knock{at}kcl.ac.uk

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