Effects of valinomycin, ouabain, and potassium on glycolysis and intracellular pH of Ehrlich ascites tumor cells

Publisher Website
Google Scholar
Abstract
Both valinomycin and ouabain block reaccumulation of K+ by Ehrlich ascites tumor cells depleted of K+ and cause loss of K+ from high-K+ cells. Glucose largely reverses the effect of valinomycin and to a lesser extent that of ouabain. In cells depleted of K+, glucose utilization and lactate production are impaired. Neither extracellular pH (pHe) nor intracellular pH (pHi) falls to the extent seen in non-depleted glycolyzing cells. Addition of K+ to depleted cells reverses these effects. Valinomycin increases glycolysis in K+-depleted cells but to a greater extent in nondepleted or K+-repleted cells. The increase in lactate production caused by valinomycin is accompanied by a correspondingly greater fall in pHe and pHi. Valinomycin, unlike other uncoupling agents, does not abolish the pH gradient across the plasma membrane. Increased utilization of glucose resulting from addition of K+ to K+-depleted cells or addition of valinomycin either to depleted or non-depleted cells can be entirely accounted for by increased lactate production. Ouabain blocks the stimulatory effect of added K+ on K+-depleted cells and has an inhibitory effect on glycolysis in non-depleted cells. It does not obliterate the difference in glycolytic activity between K+-depleted and nondepleted cells. Ouabain does not completely block the effect of valinomycin in augmenting glycolysis in depleted or non-depleted cells. Increased accumulation of glycolytic intermediates, particularly dihydroxyacetone phosphate, is found in glycolyzing K+-depleted cells. The most marked accumulation was found in ouabain-treated K+-deficient cells.