Desheathed frog (R. pipiens) sciatic nerves were soaked in solutions that contained ouabain or NaN3, in K-free solutions, or in K- and Ca-free solutions. Then, the nerves were allowed to recover in standard Ringer's solution. At various times during the soaking periods, some nerves were analyzed for Na and K, and estimates were made of the influx and efflux of Na22. While a nerve was soaking in any one of the experimental solutions, the Na22 influx was increased, the Na content was rising, and the K content was falling by an equivalent amount. The rate coefficient for Na22 efflux was reduced by about 25 per cent by 0.05 mM ouabain and by about 50 per cent by 5 mM NaN3. Potassium-free solutions had little effect on the rate coefficient. It was concluded that the efflux of Na from frog nerve is dependent on the metabolism, but not on the external concentration of K. The equimolar exchange that is characteristic of the net movements of Na and K in frog nerve may not be due to the presence of a tightly coupled Na-K exchange pump, but may represent a constraint imposed by the requirement for electroneutrality.

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