Importance of the non-selective cation channel TRPV1 for microglial reactive oxygen species generation.
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.
Schilling
Tom
T
Division of Basic Medical Sciences, St George's, University of London, London, UK.
Eder
Claudia
C
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*
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