Effect of cytosolic Mg2+ on mitochondrial Ca2+ signaling

• Published in: Pflügers Archiv Vol. 457; no. 4; pp. 941 - 954
• Main Authors: Szanda, Gergő, Rajki, Anikó, Gallego-Sandín, Sonia, Garcia-Sancho, Javier, Spät, András
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2009; Springer Nature B.V
• Subjects: Adenosine Triphosphate - metabolism; Animals; Binding sites; Biomedical and Life Sciences; Biomedicine; Calcium - metabolism; Calcium Signaling - physiology; Cell Biology; Cell Line; Cytoplasm - metabolism; Human Physiology; Humans; Inositol 1,4,5-Trisphosphate - metabolism; Magnesium - metabolism; Mitochondria - metabolism; Molecular Medicine; Neurosciences; Receptors; Signaling and Cell Physiology; Mitochondria; uptake; Magnesium; ATP; signal; Ca; Inositol 1,4,5-trisphosphate
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-008-0551-0

Cytosolic Ca 2+ signals are followed by mitochondrial Ca 2+ uptake, which, in turn, modifies several biological processes. Mg 2+ is known to inhibit Ca 2+ uptake by isolated mitochondria, but its significance in intact cells has not been elucidated. In HEK293T cells, activation of purinergic receptors with extracellular ATP caused cytosolic Ca 2+ signals associated with parallel changes in cytosolic [Mg 2+ ]. Neither signals were affected by omitting bivalent cations from the extracellular medium. The effect of store-operated Ca 2+ influx on cytosolic Mg 2+ concentration ([Mg 2+ ] c ) was negligible. Uncaged Ca 2+ displaced Mg 2+ from cytosolic binding sites, but for an equivalent Ca 2+ signal, the change in [Mg 2+ ] was significantly smaller than that measured after adding extracellular ATP. Inositol 1,4,5-trisphosphate mobilized Ca 2+ and Mg 2+ from internal stores in permeabilized cells. The increase of [Mg 2+ ] in the range that occurred in ATP-stimulated cells inhibited mitochondrial Ca 2+ uptake in permeabilized cells without affecting mitochondrial Ca 2+ efflux. Therefore, the Mg 2+ signal generated by Ca 2+ mobilizing agonists may attenuate mitochondrial Ca 2+ uptake.