On the mode of action of ethacrynic acid, using the barnacle muscle fiber as a model

External application of 10−4 M ethacrynic acid at pH 7.8 is usually without effect on the Na efflux into a 10 mM HCO3− solution. At an external pH of 6.8, however, 10−3 M ethacrynic acid causes a gradual rise in the loss of Na into a solution the initial HCO3- concentration of which is 5 mM. Lowering the external pH of this solution to 5.8 results in a reversal of the slow rise in Na loss. External application of 10−5 M ethacrynic at pH 6.9 and pH 6.3 is unaccompanied by a rise in the Na efflux into a Ca2+-free solution the initial HCO3− concentration of which is 5 mM. External application of 10−3 M ethacrynic acid following stimulation of the Na efflux into a Ca2+-free solution by reducing the external pH from 7.8 to 6.3 results in a large fall in the rate of loss of Na. These results indicate that the CO2-sensitive Na efflux is the principal site at which ethacrynic acid acts.