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1. The changes of the ion content and of the membrane potential of taenia coli cells have been studied during prolonged exposure to Na-deficient solutions containing either Li or choline.

2. A K-free solution containing either 71 mM-Na-71 mM-Li or 71 mM-Na-71 mM choline causes a slower loss of cellular K than a 142 mM-Na solution. In both these Na-deficient solutions the membrane hyperpolarizes to about -100 mV for periods up to 6 hr. This hyperpolarization is partially abolished by 2 x 10^-5 M ouabain.

3. Replacing all extracellular Na by Li and maintaining 5.9 mM-K causes a fast loss of all Na and a progressive replacement of K by Li. These changes of the intracellular ion content are accompanied by a depolarization of the cells, suggesting that intracellular Li cannot substitute for Na in activating the ion pump.

4. Exposing K-depleted cells to a K-free 71 mM-Na-71 mM-Li solution results in a ouabain sensitive transport of Na and Li against their electro-chemical gradient.

5. The K-uptake by K-depleted cells from a solution containing 0.59 mM-K is increased by reducing [Na]_o to half of its normal value. This finding indicates that external Na inhibits the active Na-K exchange.

6. In Na-enriched tissues half of the Na efflux is due to a ouabain insensitive Na-exchange diffusion. If Li is used as a Na substitute, the Na-Li exchange compensates for the diminution of the Na-exchange diffusion unless ouabain is added.