On the Reversibility of the Sodium Pump in Dialyzed Squid Axons

Dear Sir: In an elegant series of experiments Brinley and Mullins (1967, 1968) have examined the active and passive fluxes of sodium ions in segments of internally dialyzed squid axons. These authors claim that their technique allows ion fluxes to be studied in preparations having relatively normal permeability properties. It is therefore interesting to note that there is a significant portion of the Na+ influx which depends upon the presence of internal ATP (Brinley and Mullins, 1968). Evidence is presented which makes it highly unlikely that this component of Na + influx is due to a coupled Na+:Na+-exchange diffusion. The authors conclude that this component of Na+ influx can be "formally described as a changed Na+ permeability," the change being induced by the depletion of internal ATP to I uM. The authors clearly recognize that "these observations underline the difficulty in discriminating between pumped and passive ion movements against an electrochemical gradient," and that "the presently accepted theoretical framework is inadequate to explain the observations properly since the changes observed are undoubtedly closely connected with Na pumping." It is evident that our definitions of Na+ permeability on the one hand, or the Na+ pump on the other, are greatly dependent on the pharmacological techniques used to resolve the components of tracer-determined ion fluxes. From the work of Brinley and Mullins (1968) it would appear that strophanthidin induces a constant rate of Na+ efflux regardless of the presence of ATP (above I puM), whereas it has little or no effect on Na+ influx (Mullins and Brinley, 1969). These effects, together with the effects of small uncontrolled alterations of membrane potential on the K+ fluxes (cf. Mullins and Brinley, 1969), make the interpretation of tracer fluxes a very difficult undertaking. However, there is one possible explanation of the effect of ATP depletion on the Na+ influx which has not been suggested in relation to dialyzed axons and which is