title: Elevated temperatures alter TRPV1 agonist-evoked excitability of dorsal root ganglion neurons.
abstract: The vanilloid receptor 1 (TRPV1) is activated by capsaicin, several endogenous lipids, acidic pH and elevated temperatures. Inflammatory mediators (BK, substance P) also modulate TRPV1 activity. In this study we investigated the effect of TRPV1 agonists and elevated temperatures on neuronal membrane excitability by electrophysiological techniques using freshly isolated rat dorsal root ganglion neurons (DRGs). Focal application of heated solutions demonstrated that the normal threshold (approximately 42 degrees C) of TRPV1 activation was reduced in the presence of capsaicin (1 microM) to approximately 30 degrees C. In current-clamp recordings, increasing the temperature of the solution resulted in larger membrane depolarizations and significantly altered the pattern and onset of the action potential train evoked by 1 microM capsaicin. These effects were blocked by the TRPV1 antagonist capsazepine (10 microM). In contrast to capsaicin, anandamide (10 microM) alone did not evoke action potentials, but it did alter the excitability of neurons to subsequent applications of heat (50 degrees C). Together these results provide evidence that a synergistic interaction of TRPV1 ligands and elevated temperature activates TRPV1 receptors and results in profound effects on membrane excitability.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R04PM, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064-6123, USA. Torben.Neelands@Abbott.com
authors.forename: T R
authors.initials: TR
authors.lastname: Neelands
authors.forename: M F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: C R
authors.initials: CR
authors.lastname: Faltynek
authors.forename: C S
authors.initials: CS
authors.lastname: Surowy
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D063388:Endocannabinoids; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000819:agonists / Q000502:physiology*; D013696:Temperature
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002211:Capsaicin; C078814:anandamide