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Multiple actions of anandamide on neonatal rat cultured sensory neurones
Author(s) -
Evans Rhian M,
Scott Roderick H,
Ross Ruth A
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705723
Subject(s) - capsazepine , anandamide , population , trpv1 , medicine , chemistry , endocrinology , electrophysiology , dorsal root ganglion , pertussis toxin , endocannabinoid system , cannabinoid , patch clamp , cannabinoid receptor , biophysics , receptor , antagonist , biology , neuroscience , transient receptor potential channel , sensory system , g protein , environmental health
We have investigated the effects of the endocannabinoid anandamide (AEA) on neuronal excitability and vanilloid TRPV1 receptors in neonatal rat cultured dorsal root ganglion neurones. Using whole‐cell patch‐clamp electrophysiology, we found that AEA inhibits high‐voltage‐activated Ca 2+ currents by 33±9% (five out of eight neurones) in the absence of the CB 1 receptor antagonist SR141716A (100 n M ) and by 32±6% (seven out of 10 neurones) in the presence of SR141716A. Fura‐2 fluorescence Ca 2+ imaging revealed that AEA produced distinct effects on Ca 2+ transients produced by depolarisation evoked by 30 m M KCl. In a population of neurones of larger somal area (372±20 μ m 2 ), it significantly enhanced Ca 2+ transients (80.26±13.12% at 1 μ M ), an effect that persists after pertussis toxin pretreatment. In a population of neurones of smaller somal area (279±18 μ m 2 ), AEA significantly inhibits Ca 2+ transients (30.75±3.54% at 1 μ M ), an effect that is abolished by PTX pretreatment. Extracellular application of 100 n M AEA failed to evoke TRPV1 receptor inward currents in seven out of eight neurones that responded to capsaicin (1 μ M ), with a mean inward current of −0.94±0.21 nA. In contrast, intracellular application of 100 n M AEA elicited robust inward currents in ∼62% of neurones, the mean population response was −0.85±0.21 nA. When AEA was applied to the intracellular environment with capsazepine (1 μ M ), the mean population inward current was −0.01±0.01 nA. Under control conditions, mean population current fluctuations of −0.09±0.05 nA were observed.British Journal of Pharmacology (2004) 141 , 1223–1233. doi: 10.1038/sj.bjp.0705723