@article{3057176,
    title = "Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats",
    author = "Lee, A.W. and Kyrozis, A. and Chevaleyre, V. and Kow, L.-M. and Devidze, N. and Zhang, Q. and Etgen, A.M. and Pfaff, D.W.",
    journal = "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA",
    year = "2008",
    volume = "105",
    number = "20",
    pages = "7333-7338",
    doi = "10.1073/pnas.0802760105",
    keywords = "4 aminopyridine;  alpha 1 adrenergic receptor;  alpha 1B adrenergic receptor;  alpha adrenergic receptor blocking agent;  calcium channel;  calcium channel blocking agent;  chloroethylclonidine;  estradiol;  estradiol benzoate;  estrogen;  messenger RNA;  phenylephrine;  potassium ion;  sodium channel;  sodium channel blocking agent;  tetrylammonium chloride, animal tissue;  article;  binding affinity;  brain depth stimulation;  controlled study;  female;  hyperpolarization;  hypothalamus;  hypothalamus ventromedial nucleus;  in vivo study;  lordosis;  membrane conductance;  membrane depolarization;  nerve cell;  neurotransmission;  nonhuman;  patch clamp;  priority journal;  rat;  sexual behavior;  signal transduction, 4-Aminopyridine;  Animals;  Electrophysiology;  Estradiol;  Estrogens;  Female;  Hypothalamus;  Neurons;  Norepinephrine;  Patch-Clamp Techniques;  Phenylephrine;  Potassium Channels;  Rats;  Tetraethylammonium;  Ventromedial Hypothalamic Nucleus, Rattus",
    abstract = "Estrogens act within the ventromedial nucleus of the hypothalamus (VMN) to facilitate lordosis behavior. Estradiol treatment in vivo induces α1b-adrenoreceptor mRNA and increases the density of α1B-adrenoreceptor binding in the hypothalamus. Activation of hypothalamic α1-adrenoceptors also facilitates estrogen-dependent lordosis. To investigate the cellular mechanisms of adrenergic effects on VMN neurons, whole-cell patch-clamp recordings were carried out on hypothalamic slices from control and estradiol-treated female rats. In control slices, bath application of the α1-agonist phenylephrine (PHE; 10 μM) depolarized 10 of 25 neurons (40%), hyperpolarized three neurons (12%), and had no effect on 12 neurons (48%). The depolarization was associated with decreased membrane conductance, and this current had a reversal potential close to the K+ equilibrium potential. The α1b-receptor antagonist chloroethylclonidine (10 μM) blocked the depolarization produced by PHE in all cells. From estradiol-treated rats, significantly more neurons in slices depolarized (71%) and fewer neurons showed no response (17%) to PHE. PHE-induced depolarizations were significantly attenuated with 4-aminopyridine (5 mM) but unaffected by tetraethylammonium chloride (20 mM) or blockers of Na+ and Ca2+ channels. These data indicate that α1-adrenoceptors depolarize VMN neurons by reducing membrane conductance for K+. Estradiol amplifies α1b-adrenergic signaling by increasing the proportion of VMN neurons that respond to stimulation of α1b-adrenergic receptors, which is expected in turn to promote lordosis. © 2008 by The National Academy of Sciences of the USA."
}