Importance of the non-selective cation channel TRPV1 for microglial reactive oxygen species generation

J Neuroimmunol. 2009 Nov 30;216(1-2):118-21. doi: 10.1016/j.jneuroim.2009.07.008. Epub 2009 Aug 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Cell Line
  • Cell Respiration / drug effects
  • Cell Respiration / physiology
  • Diterpenes / pharmacology
  • Encephalitis / immunology
  • Encephalitis / metabolism*
  • Encephalitis / physiopathology
  • Gliosis / immunology
  • Gliosis / metabolism*
  • Gliosis / physiopathology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Lanthanum / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Microglia / immunology
  • Microglia / metabolism*
  • NADPH Oxidases / metabolism
  • Organ Culture Techniques
  • Oxidative Stress / immunology*
  • Reactive Oxygen Species / metabolism*
  • Respiratory Burst / drug effects
  • Respiratory Burst / physiology
  • Ruthenium Red / pharmacology
  • TRPV Cation Channels / metabolism*

Substances

  • Diterpenes
  • Reactive Oxygen Species
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Ruthenium Red
  • Lanthanum
  • resiniferatoxin
  • NADPH Oxidases
  • capsazepine
  • Capsaicin