Carini R, Bellomo G, Dianzani M U, Albano E
Dept. of Experimental Medicine and Oncology, University of Torino, Novara, Italy.
Biochem Biophys Res Commun. 1994 Jul 15;202(1):360-6. doi: 10.1006/bbrc.1994.1936.
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.
甲萘醌和三乙基铅导致分离的肝细胞内ATP耗竭，这与细胞内酸中毒以及细胞内Na⁺和Ca²⁺浓度持续升高有关。从孵育培养基中去除Na⁺以及加入乙二醇双四乙酸（EGTA）在很大程度上阻止了胞质Ca²⁺的增加，因此表明Ca²⁺是响应Na⁺负荷从细胞外介质中动员而来的。为了进一步验证这些发现，将肝细胞与丙酸钠和哇巴因联合孵育，以诱导细胞内酸中毒并抑制Na⁺外排。这种处理促进了细胞内Na⁺和Ca²⁺浓度的显著增加，从孵育培养基中省略Na⁺以及使用抑制细胞Na⁺内流的试剂可阻止这种增加。这些数据表明，在Na⁺负荷后，Ca²⁺可通过以反向模式运行的Na⁺/Ca²⁺反向转运体在肝细胞中积累。
