17β-estradiol at physiological concentrations augments Ca 2+-activated K+ currents via estrogen receptor β in the gonadotropin-releasing hormone neuronal cell line GT1-7

Abstract

Estrogens play essential roles in the neuroendocrine control of reproduction. In the present study, we focused on the effects of 17β-estradiol (E2) on the K+ currents that regulate neuronal cell excitability and carried out perforated patchclamp experiments with the GnRH-secreting neuronal cell line GT1-7. We revealed that a 3-d incubation with E2 at physiological concentrations (100 pM to 1 nM) augmented Ca 2+-activated K+ [K(Ca)] currents without influencing Ca2+-insensitive voltage-gated K+ currents in GT1-7 cells. Acute application of E2 (1 nM) had no effect on the either type of K + current. The augmentation was completely blocked by an estrogen receptor (ER) antagonist, ICI-182,780. An ERβ-selective agonist, 2,3-bis(4-hydroxyphenyl)-propionitrile, augmented the K(Ca) currents, although an ER-selective agonist, 4,4′,4″-[4-propyl-(1H)-pyrazole-1,3,5- triyl]tris-phenol, had no effect. Knockdown of ERβ by means of RNA interference blocked the effect of E2 on the K(Ca) currents. Furthermore, semiquantitative RT-PCR analysis revealed that the levels of BK channel subunit mRNAs for α and β4 were significantly increased by incubating cells with 300 pM E2 for 3 d. In conclusion, E2 at physiological concentrations augments K(Ca) currents through ERβ in the GT1-7 GnRH neuronal cell line and increases the expression of the BK channel subunit mRNAs, α and β4. Copyright © 2008 by The Endocrine Society.