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

Item Type:Article
Title:Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia
Creators Name:Kraft, R. and Grimm, C. and Grosse, K. and Hoffmann, A. and Sauerbruch, S. and Kettenmann, H. and Schultz, G. and Harteneck, C.
Abstract:Microglial cells are the host macrophages in the central nervous system and respond to brain injury and various neurological diseases. In this process, microglial cells undergo multiple morphological and functional changes from the resting cell toward a fully activated, phagocyting tissue macrophage. In culture, bacterial lipopolysaccharide (LPS) is a frequently used tool to induce this activation. By using calcium-imaging and patch-clamp techniques, we investigated the effect of hydrogen peroxide (H 2O 2), which is released by macrophagic cells themselves, on the intracellular calcium concentration and ion currents in cultured rat microglia. Application of 0.1-5 mM H 2O 2 for several minutes induced small responses in untreated cells but a large calcium influx and cation current in LPS-treated cells. In both untreated and LPS-treated microglia, internal perfusion of ADP-ribose (ADPR) via the patch pipette elicited large cation currents. Both stimuli, H 2O 2 and ADPR, have been reported to activate the recently cloned nonselective cation channel TRPM2. RT-PCR analysis from cultured rat glial and neuronal cells confirmed a strong expression of TRPM2 in rat microglia but not in astrocytes and cerebellar granule cells. In situ hybridizations from mouse brain showed a distribution of TRPM2, which is compatible with the expression in microglial cells. In conclusion, we describe here a novel calcium influx pathway in microglia coupled to hydrogen peroxide and ADPR and provide evidence that this pathway involves TRPM2. The increased sensitivity to H 2O 2 in LPS-stimulated cells suggests a role for TRPM2 in the calcium signaling of activated microglia.
Keywords:Activated Microglia, H 2O 2, Nonselective Cation Channel, Transient Receptor Potential Channel, Animals, Mice, Rats
Source:American Journal of Physiology Cell Physiology
Publisher:American Physiological Society
Page Range:C129-C137
Date:1 January 2004
Official Publication:https://doi.org/10.1152/ajpcell.00331.2003
PubMed:View item in PubMed

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