17-beta-estradiol modulation of area postrema potassium currents.
The purpose of this study was to determine the effects of 17-beta-estradiol on area postrema neuronal activity in vivo and on area postrema potassium currents (IK) in vitro. In anesthetized rats, intravenous injection of 17-beta-estradiol (10 ng/kg bw) -inhibited area postrema neuronal activity in 8/8 neurons tested. The averaged firing rate decreased from 2.9 +/- 1.1 to 1.1 +/- 0.3 Hz. The inhibitory effects of 17-beta-estradiol on area postrema neuronal activity were rapid in onset (within 1 min) and long-lasting (>8 min). To study the cellular mechanisms involved in this response, the effects of 17-beta-estradiol were examined in dissociated area postrema neurons. In these cells, 17-beta-estradiol (0.5 nM) increased the averaged peak IK 27 +/- 8%. The time course for the potentiation was observed within approximately 0.5-1 min after the application of 17-beta-estradiol. Full recovery from the potentiation usually occurred within approximately 3-4 min after the washout of 17-beta-estradiol. The biologically inactive 17-alpha-estradiol had no effect on area postrema IK and the 17-beta-estradiol antagonist, ICI 182,780 blocked the effects of 17-beta-estradiol on area postrema IK. Finally, big conductance calcium-activated potassium current (MaxiK(+)) was identified in area postrema neurons (n = 12/12). Blockade of MaxiK(+) with 100 nM iberiotoxin blocked the effects of 17-beta-estradiol on IK. These results suggested 17-beta-estradiol might modulate area postrema neuronal activity by increasing MaxiK(+) current.
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Dalton Cardiovascular Research Center, Department of Veterinary Biomedical Sciences, University of Missouri, Columbia, Missouri 65211, USA.
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D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D007275:Injections, Intravenous; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D004965:Estrogen Antagonists; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D000077267:Fulvestrant; D004958:Estradiol; C064719:iberiotoxin; D011188:Potassium