Molecular basis of the permeabilization of mammalian cells by ionophores.

Mammalian cells become permeable to low-molecular-weight compounds and proteins when they are treated with nigericin. Concentrations of this ionophore that have no effect on protein synthesis induce the entry of the translation inhibitors hygromycin B (Mr 550) and kappa-sarcin (Mr 16800). Treatment of HeLa cells with low concentrations of nigericin stimulate the (Na+/K+)ATPase and, as a consequence, increase the plasma membrane potential. A correlation is observed between the increase in membrane potential and the entry of antibiotics and protein toxins into cells. These results suggest a relationship between the two phenomena and help an understanding of the molecular mechanism for the passage of charged molecules and proteins into mammalian cells. This permeabilization is specific for certain ionophores, such as nigericin and monensin, and does not occur on treatment with amphotericin B, valinomycin or A23187. These compounds depolarize the plasma membrane and drastically block protein synthesis in HeLa cells under these conditions.