Effects of Fluoride on Potassium and Sodium Permeability of the Erythrocyte Membrane

One of the most important features of cell membranes is their capacity to discriminate between ions of different sign or different chemical nature. In the erythrocyte membrane, coulombic forces seem to govern the discrimination between anions and cations. There is reason to believe that, without impeding the movements of anions, positive fixed charges impose a severe restriction on the movements of diffusible cations between cells and medium. But although a number of very conspicuous changes of cation permeability with pH and ionic strength can be related to variations of the fixed charge density of the membrane (Passow, 1965; LaCelle and Rothstein, 1966), observations have been made that passive cation permeability is not entirely governed by coulombic forces. In particular, it has been observed that a number of agents such as fluoride, lead, triose reductone, IAA and adenosine (Passow, 1964), and others are capable of inducing a selective increase in passive K + movements without greatly affecting Na + permeability. I t is far from being clear whether these agents act on a physiologically operating cation control mechanism or open up channels which are normally without any control function. Nevertheless, the selectivity of the effect with respect to K permeability raises the generally interesting question about the nature of K / N a discrimination in biological membranes. The present article recapitulates part of the previous work on fluoride poisoning of erythrocytes and adds new information on the site of action of the poison and on the factors controlling K / N a discrimination in the fluoride-treated membrane. The action of fluoride on washed human erythrocytes suspended in isotonic NaC1 depends not only on its own concentration but also on the concentrations of alkaline earth ions and glucose in the medium. With increasing fluoride concentration its effect on passive cation permeability passes through a maximum. Depending on the respective concentrations of alkaline earth ions at the optimal fluoride concentration of 40 mmoles/liter, three different effects on cation permeability can be distinguished. (a) In the complete absence of alkaline earth ions, i.e. in the presence of complexing agents such as EDTA (Gardos, 1958; Lepke and Passow, 1959) or ATP, fluoride inhibits the pump without affecting passive cation permeability. K + leaves