Acute estradiol application increases inward and decreases outward whole-cell currents of neurons in rat hypothalamic ventromedial nucleus.
Acute estradiol (E2) can potentiate the excitatory responses of hypothalamic ventromedial nucleus (VMN) neurons to neurotransmitters. To investigate the mechanism(s) underlying the potentiation, the whole-cell patch voltage clamp technique was used to study VMN neurons in hypothalamic slices prepared from female juvenile (3-5 weeks) rats. A voltage step and/or ramp was applied every 5 min to evoke whole-cell currents before, during and after a treatment with E2 (10 nM), corticosterone (10 nM) or vehicle for up to 20 min. Acute E2 increased inward currents in 38% of neurons tested. Their average peak inward current amplitudes started to increase within 5 min and reached the maximum of 163% of pretreatment level (Pre) at 20 min of treatment before recovering toward Pre. These increases are significantly greater than the Pre and corresponding vehicle controls and non-responsive neurons. Outward currents were decreased significantly by E2 in 27% of E2-treated cells, down to 60% of Pre levels. E2 also appeared to affect the kinetics of the inward and outward currents of estrogen-responsive neurons. Whenever observed, the effects of acute E2 were reversible after a 5- to 10-min washing. Probability analysis indicates that E2 affected the inward and the outward currents independently. The E2 effects are specific in that they were not produced by similar treatment with vehicle or corticosterone. Pharmacological characterizations using ion replacement and channel blockers showed that the inward currents were mediated practically all by Na(+) and the outward currents mainly by K(+). Thus, acute E2 can enhance inward Na(+) and attenuate outward K(+) currents. Since both effects will lead to an increase in neuronal excitability, they may explain our previous observation that E2 potentiates the excitation of VMN neurons.
Kow
L-M
LM
Laboratory of Neurobiology and Behavior, The Rockefeller University, 1230 York Avenue, Box 336, New York, NY 10021-6399, USA. kowl@rockefeller.edu
Devidze
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N
Pataky
S
S
Shibuya
I
I
Pfaff
D W
DW
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D004958:Estradiol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology* / Q000187:drug effects*
D002121:Calcium Channel Blockers; D051668:Delayed Rectifier Potassium Channels; D018690:Excitatory Amino Acid Agonists; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D002104:Cadmium; D013779:Tetrodotoxin; D004958:Estradiol; D016202:N-Methylaspartate; D019789:Tetraethylammonium; D006632:Histamine