Adenosine triphosphate depletion by cyanide results in a Na+-dependent Mg2+ 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 Mg2+. This extrusion starts after a 10-minute lag phase and reaches a maximum of 35 to 40 nmol Mg2+ per milligram protein within 60 minutes from the addition of CN−. A quantitatively similar Mg2+ 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 Mg2+ 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 Ca2+ or K+, or the addition of amiloride. An acidic extracellular pH or the removal of extracellular HCO3− inhibits the cyanide-induced Mg2+ extrusion by at least 80%. Taken together, these data suggest that the decrease in cellular adenosine triphosphate content removes a major Mg2+ complexing agent from the hepatocyte and results in an extrusion of hepatic Mg2+ exclusively through a Na+-dependent exchange mechanism modulated by acidic changes in extracellular pH.