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Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia

Robert Kraft1, Christian Grimm, Karin Grosse

  • 1Institut für Pharmakologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Thielallee 69-73, 14195 Berlin, Germany.

American Journal of Physiology. Cell Physiology
|September 27, 2003
PubMed

Insights

Hydrogen peroxide and ADP-ribose activate a novel calcium influx pathway in microglia, primarily involving the TRPM2 channel. This pathway is more sensitive in activated microglial cells, suggesting a role in neurological disease.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Microglial cells act as the central nervous system's macrophages, responding to injury and disease.
  • Activation involves morphological and functional changes, often induced by bacterial lipopolysaccharide (LPS) in culture.
  • Hydrogen peroxide (H2O2) is released by macrophages and can influence cellular responses.

Purpose of the Study:

  • To investigate the effects of H2O2 on intracellular calcium concentration and ion currents in cultured rat microglia.
  • To identify the ion channel involved in H2O2- and ADP-ribose (ADPR)-induced calcium influx in microglia.
  • To explore the role of TRPM2 in microglial activation and calcium signaling.

Main Methods:

  • Calcium imaging and patch-clamp techniques were used on cultured rat microglia.
  • Cells were treated with H2O2 and ADPR to assess responses.
  • Reverse transcription-PCR (RT-PCR) and in situ hybridization were employed to analyze TRPM2 expression.

Main Results:

  • H2O2 induced significant calcium influx and cation currents in LPS-treated microglia, but not in untreated cells.
  • Both H2O2 and ADPR elicited large cation currents in both untreated and LPS-treated microglia.
  • RT-PCR confirmed strong TRPM2 expression in microglia, with in situ hybridization showing compatible distribution in the mouse brain.

Conclusions:

  • A novel calcium influx pathway involving H2O2 and ADPR was identified in microglia.
  • Evidence suggests this pathway is mediated by the TRPM2 channel.
  • Increased H2O2 sensitivity in LPS-stimulated microglia indicates TRPM2's role in activated microglial calcium signaling.

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