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8-Bromo-cAMP blocks opioid activation of a voltage-gated potassium current in isolated hippocampal neurons

T L Wimpey1, C Chavkin

  • 1Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.

Neuroscience Letters
|March 16, 1992
PubMed

Insights

Opioid agonists activate potassium channels in rat hippocampus neurons. This activation is blocked by cAMP, suggesting cAMP-dependent phosphorylation regulates these channels.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Mu-selective opioid agonists activate potassium conductances in rat hippocampal non-pyramidal neurons.
  • Two distinct potassium conductances, inward rectifying and voltage-gated, are activated by these agonists.

Purpose of the Study:

  • To investigate the intracellular signaling pathways regulating the opioid-activated voltage-gated potassium conductance.
  • To determine the role of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in this process.

Main Methods:

  • Electrophysiological recordings in acutely dissociated rat hippocampal non-pyramidal neurons.
  • Application of mu-selective opioid agonists.
  • Pharmacological manipulation using membrane-permeable cAMP and cGMP analogues (8-bromo-cAMP and 8-bromo-cGMP).

Main Results:

  • The opioid-activated voltage-gated potassium conductance was inhibited by 8-bromo-cAMP.
  • 8-bromo-cGMP did not affect the opioid-activated voltage-gated potassium current.
  • These findings indicate a specific role for cAMP in modulating this neuronal response.

Conclusions:

  • The opioid-activated potassium channel in rat hippocampal neurons is regulated by cAMP-dependent phosphorylation.
  • This mechanism provides insight into the downstream signaling of opioid receptor activation in the hippocampus.

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