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- Title
Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites.
- Authors
Evans, R. M.; Wease, K. N.; MacDonald, C. J.; Khairy, H. A.; Ross, R. A.; Scott, R. H.
- 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 μM 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.British Journal of Pharmacology (2008) 154, 480–492; doi:10.1038/bjp.2008.93; published online 31 March 2008
- Subjects
SENSORY neurons; POTASSIUM; PHARMACOLOGY; METABOLITES; NERVOUS system; CALCIUM metabolism; POTASSIUM metabolism; ACTION potentials; AMIDASES; AMIDES; ANIMAL experimentation; ANIMAL populations; ARACHIDONIC acid; CELL culture; CELL receptors; COMPARATIVE studies; CYTOLOGICAL techniques; DRUGS; ELECTRIC stimulation; ENZYME inhibitors; SENSORY ganglia; RESEARCH methodology; MEDICAL cooperation; MICROSCOPY; NEUROTRANSMITTERS; POTASSIUM chloride; RATS; RESEARCH; SULFUR compounds; EVALUATION research; CHEMICAL inhibitors; PHARMACODYNAMICS
- Publication
British Journal of Pharmacology, 2008, Vol 154, Issue 2, p480
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/bjp.2008.93