Τίτλος:
Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Lee, A.W.
Kyrozis, A.
Chevaleyre, V.
Kow, L.-M.
Devidze, N.
Zhang, Q.
Etgen, A.M.
Pfaff, D.W.
Περιοδικό:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
Λέξεις-κλειδιά:
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
DOI:
10.1073/pnas.0802760105
