Opioids hyperpolarize β-endorphin neurons via μ-receptor activation of a potassium conductance

Martin J. Kelly, Michael D. Loose, Oline K. Ronnekleiv

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Intracellular recordings were made from hypothalamic arcuate (ARC) neurons with biocytin-filled electrodes under current- and voltage-clamp in slices prepared from ovariectomized guinea pigs which were pretreated with estradiol. Forty-three neurons were identified after linking the intracellular biocytin with streptavidin-FITC and subsequently were examined for β-endorphin immunoreactivity. Ten of these neurons were immunoreactive for β-endorphin. β-Endorphin neurons displayed the following passive membrane properties: RMP:-56 ± 2 mV; Rin: 439 ± 66 MG; τ: 17.5 ± 2.4 ms; and often fired spontaneously (5.9 ± 2.2 Hz). These membrane characteristics were not different from identified neurons in the ARC that were not immunoreactive for ᵝ endorphin. β-Endorphin neurons exhibited instantaneous inward rectification and time-dependent rectification. The μ-opioid agonist Tyr-D-Ala-Gly-MePhe-Gly-oI (DAGO) decreased spontaneous firing, induced membrane hyperpoiarization (12 ± 2 mV; range 6–22 m V) and decreased the Rin (38 ± 4%) of the β-endorphin neurons. These effects of DAGO were blocked by the opioid antagonist naloxone (I pAT) and were not blocked by 1 μMTTX. DAGO-responsive cells were unaffected by either k- or δ-receptor opioid agonists. These results indicate that p-receptors may be autoreceptors on ARC β-endorphin neurons and that activation of opioid p-receptors hyperpolarizes β-endorphin neurons via an increase in K+conductance. Therefore, opioid peptides may modulate opioid tone through an ‘ultra-short loop’ feedback control mechanism.

Original languageEnglish (US)
Pages (from-to)268-275
Number of pages8
Issue number3
StatePublished - 1990


  • Arcuate
  • Autoreceptor
  • Hyperpolarization
  • Hypothalamus
  • K<sup>+</sup>conductance
  • Voltage clamp
  • β-Endorphin
  • μ-Opioid receptor

ASJC Scopus subject areas

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


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