Cytosolic free magnesium, ATP, and blebbing during chemical hypoxia in cultured rat hepatocytes

Biphasic effect of extra-reticular Mg2+ on hepatic G6P transport and hydrolysis

“…Yet, the stimulatory effect occurs at a concentration that is not physiological for the hepatocyte. As attested by 31 P-NMR [3] or fluorescence indicator [27] measurements, cytoplasmic Mg 2+ level ranges between 0.5-0.7 mM under basal, un-stimulated conditions. Total and free Mg 2+ concentrations, however, decrease significantly under diabetic conditions [20,28] or prolonged exposure to ethanol [29], reaching values close to the concentration of 0.25mM tested here.…”

Magnesium in the Central Nervous System

“…Mg 2+ , however, can also be extruded following the treatment with various agents that impact cellular ATP content and production. Cyanide (Harman et al, 1990;Dalal andRomani, 2010), mitochondrial uncouplers (Akerman, 1981;Kubota et al, 2005), fructose (Gaussin et al, 1997), ethanol (Tessman and Romani, 1998), or hypoxia (Gasbarrini et al, 1992 are just some of the agents whose addition impact cellular Mg 2+ homeostasis. All these agents, in fact, have in common that they decrease cellular ATP content by either preventing the mitochondrial electron chain from generating ATP at various levels (cyanide or uncouplers), or by acting as an ATP trap (fructose), or by altering the redox state of pyridine nucleotide within the mitochondrion or the cell (ethanol).…”

“…All these agents, in fact, have in common that they decrease cellular ATP content by either preventing the mitochondrial electron chain from generating ATP at various levels (cyanide or uncouplers), or by acting as an ATP trap (fructose), or by altering the redox state of pyridine nucleotide within the mitochondrion or the cell (ethanol). As ATP represents the major buffering component for Mg 2+ within the cell (Scarpa and Brinley, 1981;Luthi et al, 1999), a decrease in this phosphonucleotide moiety results in an increase in cytosolic free [Mg 2+ ]i, and ultimately in a detectable extrusion from the cell (Harman et al, 1990;Gasbarrini et al, 1992;Gaussin et al, 1997;Tessman and Romani, 1998;Dalal and Romani, 2010). The Mg 2+ extrusion can be observed to a larger extent in erythrocytes, which possess limited cellular buffering capacity and no compartmentation (Hwa et al, 1993), but it can also be observed in cells that present additional buffering by proteins or cellular organelles in addition to phosphonucleotides (Harman et al, 1990;Gasbarrini et al, 1992;Gaussin et al, 1997;Tessman and Romani, 1998;Dalal and Romani, 2010).…”

“…As ATP represents the major buffering component for Mg 2+ within the cell (Scarpa and Brinley, 1981;Luthi et al, 1999), a decrease in this phosphonucleotide moiety results in an increase in cytosolic free [Mg 2+ ]i, and ultimately in a detectable extrusion from the cell (Harman et al, 1990;Gasbarrini et al, 1992;Gaussin et al, 1997;Tessman and Romani, 1998;Dalal and Romani, 2010). The Mg 2+ extrusion can be observed to a larger extent in erythrocytes, which possess limited cellular buffering capacity and no compartmentation (Hwa et al, 1993), but it can also be observed in cells that present additional buffering by proteins or cellular organelles in addition to phosphonucleotides (Harman et al, 1990;Gasbarrini et al, 1992;Gaussin et al, 1997;Tessman and Romani, 1998;Dalal and Romani, 2010). In the case of fructose, the changes in cytosolic Mg 2+ have been associated with an activation of the glycogen phosphorylase, which ultimately results in glycogenolysis activation and glucose utilization to restore ATP levels (Gaussin et al, 1997).…”

“…Heretofore, a role of Mg 2+ as transient regulator of cytosolic enzymes appears to be unlikely. It has to be noted that even under conditions in which hormonal and non--hormonal stimuli elicit major fluxes of Mg 2+ across the cell plasma membrane in either direction, massive translocations of Mg 2+ that increase or decrease the total cellular Mg 2+ content by 1 to 2mM (or 5--10% of total cell content) result in minor or no changes in cytosolic free [Mg 2+ ] i (Harman et al, 1990;. This disconnect can be explained by assuming that the source or destination of transported Mg 2+ is a cellular compartment or organelle, or a major binding site, or that Mg 2+ is highly buffered.…”