The effects of nigericin, valinomycin, and 2,4-dinitrophenol on intracellular pH, glycolysis, and K + concentration of ehrlich ascites tumor cells

Abstract

The effects of nigericin, valinomycin, 2,4-dinitrophenol, and combinations of these drugs on intracellular pH (pH i), glycolysis, and K + concentrations of Ehrlich ascites tumor cells have been studied. All of the drugs and combinations raised extracellular pH (pH e) and lowered pH i in non-glycolyzing cells. All drugs administered with glucose except nigericin increased the rate of glycolysis and produced lower values of pH e and pH i than did glucose alone. Nigericin caused some increase in the rate of lactate production with little if any effect on glucose utilization. The values of pH e and pH i obtained with glycolyzing cells treated with nigericin alone and in combination with valinomycin indicate effective transfer of H + from the external medium into the cells, presumably in exchange for K +. All drugs and combinations caused loss of cellular K + that was partially inhibited by glucose. The effects of nigericin and valinomycin on K + loss were additive. Those of dinitrophenol and valinomycin were not. The effects of dinitrophenol and valinomycin are attributed to depletion of ATP required for Na +-K + membrane transport. An additional effect of nigericin may be promotion of K +-H + exchange across the plasma membrane. The combination of valinomycin plus dinitrophenol does not have an effect equivalent to that of nigericin on the plasma membrane.