Estradiol inhibits Ca2+ and K+ channels in smooth muscle cells from pregnant rat myometrium

The purpose of this study was to investigate the actions of 17 beta-estradi ol on the electrical activity of pregnant rat myometrium. The longitudinal layer of the myometrium was dissected from pregnant rats (17 to 19 days of gestation), and single cells were isolated by enzymatic digestion. Calcium currents and potassium currents were recorded by the whole-cell voltage-cla mp method, and the single calcium-dependent potassium current was recorded by the outside-out patch-clamp method. The effects of 17 beta-estradiol on these currents were investigated. When a myometrial cell was held at - 50 m V, depolarization to a potential more positive than - 30 mV produced an inw ard current followed by a slowly developing outward current. Application of tetraethylammonium inhibited the outward current while the inward current was completely abolished in a calcium-free solution. Estradiol at high conc entrations (> 3 mu M) inhibited both inward and outward currents in a volta ge-dependent manner. Removal of estradiol restored the amplitude of the out ward but not of the inward current. Estradiol (30 mu M) also inhibited the activity of single calcium-dependent potassium channels without changing si ngle channel conductance. In conclusion, estradiol at high concentrations i nhibited: (1) voltage-dependent calcium, (2) calcium-dependent potassium an d (3) voltage-dependent potassium currents. These actions of estradiol woul d prevent action potential generation and after-hyperpolarizations. Suppres sion of the after-hyperpolarization might further prevent spike generation due to slowing of the calcium channel's recovery from the inactivated state . (C) 1999 Elsevier Science B.V. All rights reserved.