Estrogen modulation of K+ channel activity in hypothalamic neurons involved in the control of the reproductive axis

Martin Kelly, Oline Ronnekleiv, Nurhadi Ibrahim, Andre H. Lagrange, Edward J. Wagner

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Here we report on the progress we have made in elucidating the mechanisms through which estrogen alters synaptic responses in hypothalamic neurons. We examined the modulation by estrogen of the coupling of various receptor systems to inwardly rectifying and small conductance, Ca2+-activated K+ (SK) channels. We used intracellular sharp-electrode and whole-cell recordings in hypothalamic slices from ovariectomized female guinea pigs. Estrogen rapidly uncouples μ-opioid receptors from G protein-gated inwardly rectifying K+ (GIRK) channels in β-endorphin neurons, manifest by a reduction in the potency of μ-opioid receptor agonists to hyperpolarize these cells. This effect is blocked by inhibitors of protein kinase A and protein kinase C. Estrogen also uncouples γ-aminobutyric acid (GABA)B receptors from the same population of GIRK channels coupled to μ-opioid receptors. At 24 h after steroid administration, the GABAB/GIRK channel uncoupling observed in GABAergic neurons of the preoptic area (POA) is associated with reduced agonist efficacy. Conversely, estrogen enhances the efficacy of α1-adrenergic receptor agonists to inhibit apamin-sensitive SK currents in these POA GABAergic neurons, and does so in both a rapid and sustained fashion. Finally, we observed a direct, steroid-induced hyperpolarization of both arcuate and POA neurons, among which gonadotropin-releasing hormone (GnRH) neurons are particularly sensitive. These findings indicate a richly complex yet coordinated steroid modulation of K+ channel activity that serves to control the excitability of hypothalamic neurons involved in regulating the reproductive axis.

Original languageEnglish (US)
Pages (from-to)447-456
Number of pages10
JournalSteroids
Volume67
Issue number6
DOIs
StatePublished - 2002

Fingerprint

Neurons
Estrogens
Inwardly Rectifying Potassium Channel
Modulation
Preoptic Area
Opioid Receptors
GABAergic Neurons
Steroids
GABA-B Receptors
Endorphins
Apamin
Aminobutyrates
Calcium-Activated Potassium Channels
Adrenergic Agonists
Patch-Clamp Techniques
Cyclic AMP-Dependent Protein Kinases
GTP-Binding Proteins
Gonadotropin-Releasing Hormone
Protein Kinase C
Electrodes

Keywords

  • β-Endorphin
  • Estrogen
  • GABA
  • K Channel
  • Norepinephrine
  • Protein kinase

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Estrogen modulation of K+ channel activity in hypothalamic neurons involved in the control of the reproductive axis. / Kelly, Martin; Ronnekleiv, Oline; Ibrahim, Nurhadi; Lagrange, Andre H.; Wagner, Edward J.

In: Steroids, Vol. 67, No. 6, 2002, p. 447-456.

Research output: Contribution to journalArticle

Kelly, Martin ; Ronnekleiv, Oline ; Ibrahim, Nurhadi ; Lagrange, Andre H. ; Wagner, Edward J. / Estrogen modulation of K+ channel activity in hypothalamic neurons involved in the control of the reproductive axis. In: Steroids. 2002 ; Vol. 67, No. 6. pp. 447-456.
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