Channelpedia

PubMed 20660067


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir6.2



Title: 17{beta}-Estradiol Rapidly Increases ATP-Sensitive Potassium Channel Activity in Gonadotropin-Releasing Hormone Neurons via a Protein Kinase Signaling Pathway.

Authors: Chunguang Zhang, Martin J Kelly, Oline K Rønnekleiv

Journal, date & volume: , 2010 Jul 21 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20660067


Abstract
17Beta-estradiol (E2) both inhibits and excites GnRH neurons via presynaptic as well as postsynaptic mechanisms. Although it has been demonstrated that E2 can alter the excitability of GnRH neurons via direct actions, the intracellular signaling cascades mediating these actions are not well understood. Previously we have shown that the activity of one of the critical ion channels needed for maintaining GnRH neurons in a hyperpolarized state, the ATP-sensitive potassium channel (K(ATP)) channel, is augmented by E2 in ovariectomized females. However, the mRNA expression of the K(ATP) channel subunits Kir6.2 and SUR1 are unchanged with in vivo E2 treatment. Therefore, to elucidate the cellular signaling mechanism(s) modulating the channel activity, we did whole-cell patch-clamp recording of enhanced green fluorescent protein-GnRH neurons from ovariectomized female mice to study the acute effects of E2. E2 dose-dependently (EC(50) = 0.6 nM) enhanced the diazoxide (channel opener)-activated K(ATP) channel currents by 1.2- to 2.0-fold, which was antagonized by ICI 182,780. E2-BSA was equally as effective as E2, whereas 17 alpha-estradiol [corrected] had no effect. The protein kinase A (PKA) activator forskolin mimicked the effects of E2, whereas the PKA inhibitor H89 and the protein kinase C (PKC) inhibitor bisindolylmaleimide I blocked the effects of E2. Similar to E2, STX, a membrane estrogen receptor (ER) agonist that does not bind to ERalpha or ERbeta, also potentiated the diazoxide-induced K(ATP) channel current by 1.5-fold. Therefore, E2 can potentiate K(ATP) channel activity in GnRH neurons through a membrane ER-activated PKC-PKA signaling pathway.