Adenosine triphosphate depletion by cyanide results in a Na +-dependent Mg 2+ extrusion from liver cells

Abstract

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 HCO 3 − 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.