Energetics of trout hepatocytes during A23187-induced disruption of Ca2+i homeostasis

KRUMSCHNABEL G, SCHWARZBAUM PJ, WIESER W

COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. C, COMPARATIVE PHARMACOLOGY AND TOXICOLOGY.

Elsevier

Año: 1999 p. 187 - 195

0742-8413

The impact of an increase of intracellular Ca2i on the energy metabolism of trout hepatocytes was assessed by applying theCa2 ionophore A23187 and studying the consequences of the ensuing elevation of Ca2i on various metabolic parameters. Afterapplication of A23187 no loss of viability occurred for 2 h, but glutathione content decreased by 46%. A concomitant decreaseof [ATP] as well as of Na,K-ATPase activity by over 50% could be prevented by incubating the cells in a Ca2-free medium.Upon addition of the ionophore cellular oxygen consumption more than doubled in a strictly Ca2-dependent manner, with halfof this increase being sensitive to ruthenium red, an inhibitor of the mitochondrial Ca2 uniporter. This increase in oxygenconsumption was transient in nature and at its peak it was similar in magnitude to that induced by 2,4-dinitrophenol. Similarly,oxygen consumption sensitive to the protein synthesis inhibitor cycloheximide was transiently increased by A23187, but returnedto control levels within 30 min of incubation. These results suggest that elevation of intracellular Ca2 leads to an energeticimbalance not related to stimulation of ATP consuming processes, but mainly due to impairment of mitochondrial function,possibly by the decoupling of oxidative phosphorylation and by inducing dissipative Ca2 cycling. © 1999 Elsevier Science Inc.All rights reserved.