17beta-estradiol at physiological concentrations augments Ca(2+) -activated K+ currents via estrogen receptor beta in the gonadotropin-releasing hormone neuronal cell line GT1-7.
Estrogens play essential roles in the neuroendocrine control of reproduction. In the present study, we focused on the effects of 17beta-estradiol (E2) on the K(+) currents that regulate neuronal cell excitability and carried out perforated patch-clamp 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 Ca(2+)-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 ERbeta-selective agonist, 2,3-bis(4-hydroxyphenyl)-propionitrile, augmented the K(Ca) currents, although an ERalpha-selective agonist, 4,4',4''-[4-propyl-(1H)-pyrazole-1,3,5-triyl]tris-phenol, had no effect. Knockdown of ERbeta 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 alpha and beta4 were significantly increased by incubating cells with 300 pm E2 for 3 d. In conclusion, E2 at physiological concentrations augments K(Ca) currents through ERbeta in the GT1-7 GnRH neuronal cell line and increases the expression of the BK channel subunit mRNAs, alpha and beta4.
Nishimura
Ichiro
I
Department of Physiology, Nippon Medical School, Bunkyo, Tokyo, Japan.
Ui-Tei
Kumiko
K
Saigo
Kaoru
K
Ishii
Hirotaka
H
Sakuma
Yasuo
Y
Kato
Masakatsu
M
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002461:Cell Line, Transformed; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000502:physiology*; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C465449:Kcnma1 protein, mouse; C494843:Kcnmb4 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D009570:Nitriles; D011422:Propionates; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D011188:Potassium; D002118:Calcium