Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats.
Estrogens act within the ventromedial nucleus of the hypothalamus (VMN) to facilitate lordosis behavior. Estradiol treatment in vivo induces alpha(1b)-adrenoreceptor mRNA and increases the density of alpha(1B)-adrenoreceptor binding in the hypothalamus. Activation of hypothalamic alpha(1)-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 alpha(1)-agonist phenylephrine (PHE; 10 microM) 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 alpha(1b)-receptor antagonist chloroethylclonidine (10 microM) 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 Ca(2+) channels. These data indicate that alpha(1)-adrenoceptors depolarize VMN neurons by reducing membrane conductance for K(+). Estradiol amplifies alpha(1b)-adrenergic signaling by increasing the proportion of VMN neurons that respond to stimulation of alpha(1b)-adrenergic receptors, which is expected in turn to promote lordosis.
Lee
Anna W
AW
Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10065, USA. leeaw@rockefeller.edu
Kyrozis
Andreas
A
Chevaleyre
Vivien
V
Kow
Lee-Ming
LM
Devidze
Nino
N
Zhang
Qiuyu
Q
Etgen
Anne M
AM
Pfaff
Donald W
DW
D015761:4-Aminopyridine / Q000737:chemistry; D000818:Animals; D004594:Electrophysiology / Q000379:methods; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000473:pathology*; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000737:chemistry; D051381:Rats; D019789:Tetraethylammonium / Q000737:chemistry; D014697:Ventromedial Hypothalamic Nucleus / Q000473:pathology*
D004967:Estrogens; D015221:Potassium Channels; D010656:Phenylephrine; D004958:Estradiol; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D009638:Norepinephrine