Ussing (1949) suggested that part of the observed Na efflux in frog muscle might result from a process that he termed 'exchange diffusion', involving a sodium for sodium exchange across the membrane. Thus, if a carrier with a high affinity for Na were confined to the membrane and able to diffuse across it only when it had formed a complex with Na, there would be a continual movement of labelled Na through the membrane without necessarily any simultaneous consumption of energy. If such a mechanism existed, complete removal of Na from the outside of the membrane might be expected to eliminate a substantial fraction of the total efflux of labelled Na, unless the cation substituted for Na+ could also form a complex with the carrier and thus move across the membrane. We therefore investigated the effect on the Na efflux of substituting choline or lithium for the sodium in the external medium, and found that in both cases the efflux was promptly reduced by about half when the sodium in the interfibre fluid was replaced by the foreign cation. This observation clearly warranted further analysis, and the changes in Na efflux were examined for test muscles with altered internal Na concentrations, and at various temperatures. The effect of partial replacement of external Na was also investigated and the resulting changes in Na efflux were compared with the parallel alterations in Na influx. The effect of removing external Na was found to add to that of removing external K, and the relative magnitude of the two effects was studied as a function of the Na content of the muscles.A preliminary report on this work was made at the XX International Physiological Congress (Swan & Keynes, 1956).
METHODSMeasurements of sodium fluxes For measurement of effluxes, frog muscles were dissected free and exposed to Ringer's solution containing 4Na for about 3-5 hr. This period was calculated as sufficient for the specific activity of