Evidence for a sodium-dependent calcium influx in isolated rat hepatocytes undergoing ATP depletion.
ATP depletion caused by menadione and triethyllead in isolated hepatocytes is associated with intracellular acidosis and a sustained increase in intracellular Na+ and Ca2+ concentrations. Removal of Na+ from the incubation medium as well as the inclusion of EGTA largely prevented the increase in cytosolic Ca2+, thus indicating that Ca2+ was mobilized from the extracellular medium in response to Na+ load. To further validate these findings, hepatocytes were incubated with a combination of sodium propionate and ouabain in order to induce intracellular acidosis and inhibit Na+ extrusion. This treatment promoted a marked increase in intracellular Na+ and Ca2+ concentrations that was prevented by omission of Na+ from the incubation medium as well as by agents that inhibited cellular Na+ influx. These data indicate that following Na+ load, Ca2+ can be accumulated in hepatocytes via a Na+/Ca2+ antiporter operating on a reverse mode.
Dept. of Experimental Medicine and Oncology, University of Torino, Novara, Italy.
R
R
Carini
G
G
Bellomo
M U
MU
Dianzani
E
E
Albano
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D017920:Antiporters / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D016257:Fura-2; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D013050:Spectrometry, Fluorescence; D013054:Spectrophotometry, Atomic
D017920:Antiporters; D011422:Propionates; D019831:Sodium-Calcium Exchanger; D004533:Egtazic Acid; D010042:Ouabain; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; C514135:sodium propionate; C029658:propionic acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium; D016257:Fura-2