NO/cGMP/PKG signaling pathway induces magnesium release mediated by mitoKATP channel opening in rat hippocampal neurons

Intracellular Mg2+ concentration ([Mg2+]i) and NO regulate cell survival and death. To reveal the involvement of NO in intracellular Mg2+ regulation, we visualized intracellular Mg2+ using the fluorescent Mg2+ indicator KMG-104-AM in rat hippocampal neurons. Pharmacological experiments using SNAP, 8-Br-cGMP, diazoxide and several inhibitors revealed that the NO/cGMP/Protein kinsase G (PKG) signaling pathway triggers an increase in [Mg2+]i, and that Mg2+ mobilization is due to Mg2+ release from mitochondria induced by mitoKATP channel opening. In addition, Mg2+ release is potentiated by the positive feedback loop including mitoKATP channel opening, mitochondrial depolarization and PKC activation.