¹School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK

Correspondence: Dr RH Scott, School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK. E-mail: rod.scott@abdn.ac.uk

Received 7 November 2007; Revised 29 January 2008; Accepted 13 February 2008; Published online 31 March 2008.

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 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.