title: Importance of the non-selective cation channel TRPV1 for microglial reactive oxygen species generation.
abstract: Activated microglial cells generate reactive oxygen species (ROS), which have detrimental effects in neuroinflammatory and neurodegenerative diseases. In the present study, we have identified a novel mechanism involved in microglial NADPH oxidase-mediated ROS production. In PMA-stimulated microglia, ROS production was substantially reduced upon inhibition of the non-selective cation channel TRPV1 with La(3+), ruthenium red, capsazepine and 5-iodo-resinferatoxin. Furthermore, sustained membrane depolarization, a hallmark of NADPH oxidase activity in phagocytes, was found to induce non-selective cation/TRPV1 channel activity in microglia. Together, our data suggest that TRPV1 channels are involved in regulating NADPH oxidase-mediated ROS generation in microglia.
authors.affiliation: Division of Basic Medical Sciences, St George's, University of London, London, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Schilling
authors.forename: Claudia
authors.initials: C
authors.lastname: Eder
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D004224:Diterpenes / Q000494:pharmacology; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005911:Gliosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects / Q000502:physiology; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D004224:Diterpenes; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D012430:Ruthenium Red; D007811:Lanthanum; C024353:resiniferatoxin; D019255:NADPH Oxidases; C071423:capsazepine; D002211:Capsaicin