Neurons in the rat arcuate nucleus are hyperpolarized by gabab and μ-opioid receptor agonists

Evidence for convergence at a ligand-gated potassium conductance

Michael D. Loose, Oline Ronnekleiv, Martin Kelly

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Both γ-aminobutyric acid (GABA) and the endogenous opioid peptides have pervasive effects on neuroendocrine function. This study examined the effects of selective activation of GABAB and/or μ-opioid receptors on neurons of the arcuate nucelus (ARC) of the rat hypothalamus using intracellular recording of cells in a hypothalamic slice. Some recorded neurons were filled with biocytin allowing subsequent identification and immunocytochemical evaluation for the presence of β-endorphin. ARC neurons exhibited a broad array of active and passive conductances. Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL), a μ-opioid receptor agonist, inhibited spontaneous firing, hyperpolarized 68% of ARC cells in a dose-dependent manner and increased cell conductance. Baclofen, a GABAB receptor agonist, hyperpolarized all cells tested. The reversal potentials for both the DAGOL- and baclofen-induced currents were near that of a potassium conductance. Maximal activation by either of the agonists blocked the effects of the other agonist. Identified β-endorphin cells were inhibited by both DAGOL and baclofen. The results of these in vitro studies suggest that GABAB and μ-opioid receptors are coupled to the same set of potassium channels and that these channels directly and powerfully inhibit most ARC cells, including β-endorphin neurons. We propose that convergence of inhibitory influences at the ligand-gated potassium conductance described here may be an important site of interaction for opioidergic, GABAergic and other putative neurotransmitter systems in the control of neuroendocrine circuits by the ARC.

Original languageEnglish (US)
Pages (from-to)537-544
Number of pages8
JournalNeuroendocrinology
Volume54
Issue number6
DOIs
StatePublished - 1991

Fingerprint

Arcuate Nucleus of Hypothalamus
Opioid Receptors
Potassium
alanylglycine
Ligands
Endorphins
Neurons
Baclofen
Aminobutyrates
Opioid Peptides
Potassium Channels
gamma-Aminobutyric Acid
Hypothalamus
Neurotransmitter Agents

Keywords

  • Arcuate nucleus
  • GABA<inf>B</inf>
  • Hyperpolarization
  • Hypothalamus
  • Potassium conductance
  • β-Endorphin
  • μ-Opioid

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Cellular and Molecular Neuroscience
  • Endocrine and Autonomic Systems
  • Neuroscience(all)

Cite this

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title = "Neurons in the rat arcuate nucleus are hyperpolarized by gabab and μ-opioid receptor agonists: Evidence for convergence at a ligand-gated potassium conductance",
abstract = "Both γ-aminobutyric acid (GABA) and the endogenous opioid peptides have pervasive effects on neuroendocrine function. This study examined the effects of selective activation of GABAB and/or μ-opioid receptors on neurons of the arcuate nucelus (ARC) of the rat hypothalamus using intracellular recording of cells in a hypothalamic slice. Some recorded neurons were filled with biocytin allowing subsequent identification and immunocytochemical evaluation for the presence of β-endorphin. ARC neurons exhibited a broad array of active and passive conductances. Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL), a μ-opioid receptor agonist, inhibited spontaneous firing, hyperpolarized 68{\%} of ARC cells in a dose-dependent manner and increased cell conductance. Baclofen, a GABAB receptor agonist, hyperpolarized all cells tested. The reversal potentials for both the DAGOL- and baclofen-induced currents were near that of a potassium conductance. Maximal activation by either of the agonists blocked the effects of the other agonist. Identified β-endorphin cells were inhibited by both DAGOL and baclofen. The results of these in vitro studies suggest that GABAB and μ-opioid receptors are coupled to the same set of potassium channels and that these channels directly and powerfully inhibit most ARC cells, including β-endorphin neurons. We propose that convergence of inhibitory influences at the ligand-gated potassium conductance described here may be an important site of interaction for opioidergic, GABAergic and other putative neurotransmitter systems in the control of neuroendocrine circuits by the ARC.",
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AU - Kelly, Martin

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