Intracellular pH and Glycolysis in EhrlichAscites Tumor Cells: Effect of Membrane-ActiveDrugs in Potassium Depletion

• Published in: JNCI : Journal of the National Cancer Institute 1972-12, Vol.49 (6), p.1659-1665
• Main Authors: Poole, Doris T., Butler, Thomas C., Williams, Mary E.
• Format: Article
• Language: English
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/49.6.1659

A study was made of the effects of nigericin, valinomycin, 2,4-dinitrophenol, and combinations of these drugs on glycolysis and intracellular pH of K+-depleted Ehrlich ascites tumor cells. Nigericin and ouabain were investigated in depleted cells to which K+ was restored. Valinomycin stimulation of glycolysis was reduced to a greater extent than that of dinitrophenol by K+-deficiency. Stimulation of glycolysis by nigericin was proportionately greater in K+-deficient cells than in high K+ cells. In K+-depleted cells, unlike nendepleted cells, the effects of nigericin and valinomycin were additive. In the presence or absence of valinomycin, the effect of nigericin in depleted cells was similar to that of addition of K+. This action of nigericin may be due to the redistribution of the small amount of K+ in the depleted cell. Extracellular pH values higher than can be accounted For by lactate concentrations in the medium have been observed with nondepleted cells treated with nigericin, but such values did not occur with K+-depleted cells. This supports the hypothesis that the pH anomaly is caused by a K+-H+ exchange across the plasma membrane promoted by nigericin. Nigericin inhibited the uptake of K+ by depleted cells but to a lesser extent than ouabain. Ouabain pretreatment of K+-deficient cells reduced lactate production but not glucose consumption aFter addition of K+ plus glucose or of K+ plus glucose plus nigericin. Ouabain causes diversion of glucose into pathways other than lactate production.