Estrogen rapidly attenuates a GABA(B) response in hypothalamic neurons

André H. Lagrange, Edward J. Wagner, Oline Ronnekleiv, Martin Kelly

Research output: Contribution to journalArticle

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Abstract

GABA is a predominant neurotransmitter in the hypothalamus and an important regulator of hypothalamic function. To elucidate the cellular baisis for GABAergic action in this region, we used intracellular recordings from identified hypothalamic neurons. Ninety-three percent of the mediobasal hypothalamic neurons responded to GABA(B) receptor stimulation, and the presence of bicuculline-sensitive synaptic potentials indicated a tonic, GABA(A) receptor-mediated input. Stimulation of GABA(B) receptors hyperpolarized these cells by activating an inwardly rectifying potassium conductance. We characterized GABA(B) responses by generating concentration-response curves to the GABA(B) agonist baclofen. There was heterogeneity in the responses to baclofen, with one third of the cells having low baclofen potency (EC50 = 5.0 μM). Two thirds of the neurons had a 4-fold higher potency (EC50 = 1.2 μM), larger somas and a more lateral distribution. Previous work has shown that hypothalamic GABA(B) and μ-opioid receptors open the same K+ channels and that the response to μ-opioid agonists is rapidly attenuated by 17β-estradiol (E2). In order to test the hypothesis that the coupling of GABA(B) receptors to K+ channels is also altered, baclofen concentration-response curves were generated before and after an E2 challenge (100 nM 20 min). Consistent with our hypothesis, the potency of baclofen was decreased nearly 4-fold in a subset of the cells that had a high potency response to baclofen. Furthermore, decreased baclofen potency only occurred in those cells in which E2 also altered the μ-opioid responses. Therefore, our findings suggest that a discrete subpopulation of hypothalamic neurons is sensitive to estrogen actions to alter inhibitory transmission. We propose that the alteration of GABA(B) and μ-opioid input is consistent with estrogen's rapid inhibition of the reproductive axis.

Original languageEnglish (US)
Pages (from-to)114-123
Number of pages10
JournalNeuroendocrinology
Volume64
Issue number2
Publication statusPublished - Aug 1996

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Keywords

  • γ-Aminobutyric acid
  • γ-Aminobutyric acid receptors
  • Baclofen
  • Electrophysiology
  • Gonadal steroids
  • Opioid peptides
  • Potassium conductance

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)

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