σ-Binding site ligands inhibit K+ currents in rat locus coeruleus neurons in vitro

Vu H. Nguyen, Susan L. Ingram, Michael Kassiou, MacDonald J. Christie

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Biological actions of novel σ1- and σ2-selective binding site ligands (trishomocubanes: 4-azahexacyclo [5.4.1.0.2,6.03,10.05,9.08,11]dodecanes), and the reference ligands, 1,3-di(2-tolyl)-guanidine (DTG), haloperidol, (+)-pentazocine and dextromethorphan, were studied in rat locus coeruleus neurons using intracellular and whole-cell patch clamp recordings. High concentrations of trishomocubanes produced small inward currents and affected some parameters of action potential waveforms suggesting modest potency to inhibit ionic conductances underlying action potentials. σ-Ligands produced large inward currents in the presence of μ-opioid, α2-adrenoceptor and ORL1 receptor agonists. These reversed polarity near the K+ equilibrium potential, suggesting that σ-ligands act as ligand activated K+-channel blockers or interfere with the coupling between these receptors and K+-channels. However, no correlation was found between binding affinities at σ1- or σ2-binding sites and potency to inhibit K+-currents, suggesting that these effects on K+-channels are not directly related to occupancy of σ binding sites. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalEuropean Journal of Pharmacology
Volume361
Issue number1
DOIs
StatePublished - Nov 13 1998

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Keywords

  • K channel
  • Locus coeruleus
  • Nociceptin
  • Opioid
  • Trishomocubane
  • σ Receptor

ASJC Scopus subject areas

  • Pharmacology

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