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.