Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites

R M Evans, K N Wease, C J MacDonald, H A Khairy, R A Ross, R H Scott

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background and purpose: The endogenous cannabinoid anandamide (AEA) acts at cannabinoid (CB1) and vanilloid (TRPV1) receptors. AEA also shows antinociceptive properties; although the underlying mechanism for this is not fully understood, both CB1 and TRPV1 may be involved. Voltage-activated Ca2+ channels in rat-cultured dorsal root ganglion (DRG) neurons are modulated by AEA. However, AEA in different populations of neurons enhanced or attenuated KCl-evoked Ca2+ influx; these effects were linked with soma size. The aim of this study was to determine how AEA or its metabolites might produce these variable responses.

Experimental approach: The whole cell patch-clamp technique and fura-2 Ca2+ imaging were used to characterize the actions of AEA on action potential firing and voltage-activated K+ currents and to determine whether AEA metabolism plays any role in its effects on cultured DRG neurons.

Key results: AEA attenuated multiple action potential firing evoked by 300 ms depolarizing current commands in a subpopulation of DRG neurons. Application of 1 mu M AEA attenuated voltage-activated K+ currents and the recovery of KCl-evoked Ca2+ transients. The insensitivity of these responses to the CB1 receptor antagonist rimonabant (100 nM) and preincubation of DRG neurons with pertussis toxin suggested that these actions are not CB1 receptor-mediated. Preincubating DRG neurons with the fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulphonyl fluoride (PMSF) attenuated the inhibitory actions of AEA on K+ currents and Ca2+ influx.

Conclusion and implications: These data suggest that the products of AEA metabolism by FAAH contribute to the attenuation of K+ conductances and altered excitability of cultured sensory neurons.

Original languageEnglish
Pages (from-to)480-492
Number of pages13
JournalBritish Journal of Pharmacology
Volume154
Issue number2
Early online date31 Mar 2008
DOIs
Publication statusPublished - May 2008

Keywords

  • cannabinoids
  • sensory neurons
  • potassium channels
  • anandamide
  • fatty acid amide hydrolase
  • phenylmethylsulphonylfluoride
  • arachidonic acid
  • pain
  • calcium-channel currents
  • in-situ hybridization
  • nerve growth-factor
  • cannabinoid receptor
  • hippocampal-neurons
  • DRG neurons
  • cells
  • K+
  • inhibition

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