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FEBS Lett. 2013 Aug 19;587(16):2643-8. doi: 10.1016/j.febslet.2013.06.049. Epub 2013 Jul 4.

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

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  • 1Center for Biosciences and Informatics, School of Fundamental Science and Technology, Keio University, Yokohama, Kanagawa, Japan.


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.

Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Hippocampal neuron; KMG-104; Mg(2+); Mitochondria; PKC; PKG; ROS; [Ca(2+)](i); intracellular calcium concentration; intracellular magnesium ion concentration; mitoK(ATP) channel; mitochondrial ATP sensitive potassium channel; mitochondrial inner membrane potential; protein kinase C; protein kinase G; reactive oxygen species; Δψ(m)

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