Adenosine Triphosphate Depletion by Cyanide Results in a Na(+)-dependent Mg(2+) Extrusion from Liver Cells

Addition of NaCN to isolated hepatocytes results in a marked and rapid decrease in cellular adenosine triphosphate (ATP) content, and in the extrusion of a sizable amount of cellular Mg(2+). This extrusion starts after a 10-minute lag phase and reaches a maximum of 35 to 40 nmol Mg(2+) per milligram protein within 60 minutes from the addition of CN(-). A quantitatively similar Mg(2+) extrusion is also observed after the addition of the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxy-phenylhydrazone but not that of the glycolysis inhibitor iodoacetate. The Mg(2+) extrusion is completely inhibited by the removal of extracellular Na(+) or the addition of imipramine, quinidine, or glibenclamide, whereas it persists after the removal of extracellular Ca(2+) or K(+), or the addition of amiloride. An acidic extracellular pH or the removal of extracellular HCO₃⁻ inhibits the cyanide-induced Mg(2+) extrusion by at least 80%. Taken together, these data suggest that the decrease in cellular adenosine triphosphate content removes a major Mg(2+) complexing agent from the hepatocyte and results in an extrusion of hepatic Mg(2+) exclusively through a Na(+)-dependent exchange mechanism modulated by acidic changes in extracellular pH.