The Sur1-Trpm4 channel regulates NOS2 transcription in TLR4-activated microglia
Kurland, David B × Gerzanich, Volodymyr Karimy, Jason K Woo, Seung Kyoon Vennekens, Rudi Freichel, Marc Nilius, Bernd Bryan, Joseph Simard, J Marc #
Journal of Neuroinflammation vol:13 issue:1
Harmful effects of activated microglia are due, in part, to the formation of peroxynitrite radicals, which is attributable to the upregulation of inducible nitric oxide (NO) synthase (NOS2). Because NOS2 expression is determined by Ca(2+)-sensitive calcineurin (CN) dephosphorylating nuclear factor of activated T cells (NFAT), and because Sur1-Trpm4 channels are crucial for regulating Ca(2+) influx, we hypothesized that, in activated microglia, Sur1-Trpm4 channels play a central role in regulating CN/NFAT and downstream target genes such as Nos2.