Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleNEUROPHARMACOLOGY

The Noradrenergic Inhibition of an Apamin-Sensitive, Small-Conductance Ca2+-Activated K+ Channel in Hypothalamic γ-Aminobutyric Acid Neurons: Pharmacology, Estrogen Sensitivity, and Relevance to the Control of the Reproductive Axis

Edward J. Wagner, Oline K. Rønnekleiv and Martin J. Kelly
Journal of Pharmacology and Experimental Therapeutics October 2001, 299 (1) 21-30;
Edward J. Wagner
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oline K. Rønnekleiv
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin J. Kelly
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The present study sought to determine whether small-conductance, Ca2+-activated K+ currents underlie the afterhyperpolarization (AHP) in neurons of the preoptic area (POA), a brain region important in controlling reproduction. We used an ovariectomized, female guinea pig model to test two hypotheses: 1) the current associated with the AHP (IAHP) regulates the firing rate of POA neurons and 2) amine neurotransmitters modulate it in a gonadal steroid-sensitive manner. Intracellular recordings followed by combined histofluorescence/in situ hybridization for glutamic acid decarboxylase, 65-kDa isomer, revealed that POA neurons, including γ-aminobutyric acid (GABA)ergic neurons, exhibited an AHP and spike frequency adaptation. The corresponding IAHP was sensitive to antagonism by CdCl2 (200 μM), apamin (0.3–1 μM), and dequalinium (3 μM). The β-adrenergic receptor agonist isoproterenol inhibited the IAHP in a dose-dependent, timolol-sensitive fashion. In addition, the α1-adrenergic receptor agonist methoxamine dose dependently inhibited the IAHP in a prazosin-sensitive manner and increased neuronal firing rate. Twenty-four-hour pretreatment with estradiol benzoate (EB; 25 μg, s.c.) markedly potentiated the inhibitory effect of methoxamine on the IAHP, whereas that for isoproterenol was unaffected. Similarly, bath application of 17β-estradiol (100 nM; 15–20 min) mimicked the effect of EB on the methoxamine-induced inhibition of the IAHP. Thus, POA GABAergic neurons express an apamin-sensitive channel that mediates, at least in part, the IAHP, and tempers the excitability of these cells. Furthermore, these studies demonstrate that estrogen enhances the α1-adrenergic receptor-mediated inhibition of this current.

Footnotes

  • The experiments described in this study were supported by Public Health Services Grants NS35944, NS38809, and DA05158.

  • Abbreviations:
    BK
    large-conductance
    SK
    small-conductance
    AHP
    afterhyperpolarization
    E2
    17β-estradiol
    EB
    estradiol benzoate
    GAD65
    glutamic acid decarboxylase, 65-kDa isomer
    GnRH
    gonadotropin-releasing hormone
    IAHP
    current underlying the AHP
    LH
    luteinizing hormone
    POA
    preoptic area
    TEA
    tetraethylammonium
    TTX
    tetrodotoxin
    ΔImax
    maximal inhibition of the peak current
    τinactivation
    time constant for inactivation
    SSC
    sodium chloride/sodium citrate buffer
    GABA
    γ-aminobutyric acid
    aCSF
    artificial cerebrospinal fluid
    • Received April 3, 2001.
    • Accepted June 6, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 299 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 1
1 Oct 2001
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
The Noradrenergic Inhibition of an Apamin-Sensitive, Small-Conductance Ca2+-Activated K+ Channel in Hypothalamic γ-Aminobutyric Acid Neurons: Pharmacology, Estrogen Sensitivity, and Relevance to the Control of the Reproductive Axis
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleNEUROPHARMACOLOGY

The Noradrenergic Inhibition of an Apamin-Sensitive, Small-Conductance Ca2+-Activated K+ Channel in Hypothalamic γ-Aminobutyric Acid Neurons: Pharmacology, Estrogen Sensitivity, and Relevance to the Control of the Reproductive Axis

Edward J. Wagner, Oline K. Rønnekleiv and Martin J. Kelly
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 21-30;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleNEUROPHARMACOLOGY

The Noradrenergic Inhibition of an Apamin-Sensitive, Small-Conductance Ca2+-Activated K+ Channel in Hypothalamic γ-Aminobutyric Acid Neurons: Pharmacology, Estrogen Sensitivity, and Relevance to the Control of the Reproductive Axis

Edward J. Wagner, Oline K. Rønnekleiv and Martin J. Kelly
Journal of Pharmacology and Experimental Therapeutics October 1, 2001, 299 (1) 21-30;
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Iclepertin (BI 425809) in schizophrenia-related models
  • D1 agonist vs. methylphenidate on PFC working memory
  • Obesity Thwarts Preconditioning in TBI
Show more Neuropharmacology

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics