The Na,+ Cl-, and K+ content of toad plasma and the sartorius muscle has been determined. Although the Na+ and Cl- level of the muscles in the living animal varied greatly (0 to 38.0 m.eq. per kg., and 0 to 31.8 m.eq. per kg. respectively) the K+ level was subject to a smaller variation (76.5 to 136 m.eq. per kg.). There was a direct relationship between Na+ and Cl-, which was independent of the K+ level.

There is a closely related gain of Na+ and Cl- when muscle is soaked in normal Ringer. These gains are not related to the K+ loss, frequently found on soaking.

The relationship between the three ions was studied in a large series of 124 muscles in normal Ringer. As found in vivo, there was a correlation between Na+ and Cl.- This correlation was independent of K+ content, except when this was abnormally low.

Alteration of the external NaCl level produced concomitant changes in the internal levels of these ions.

Alteration of the external KCl level produced an increase in internal Cl- similar to that found with high NaCl solutions, but the amount of K+ entering the cell was approximately one-third of the external increase.

Removal of K+ from the external solution did not result in a loss of K+ from the cell, although there was an adequate amount of Cl- present to accompany it.

The results cannot be reconciled with either a Donnan concept for the accumulation of K+, or a linked carrier system.

A theory is proposed to account for the ionic differentiation within the cell. The K+ is assumed to be adsorbed onto an ordered intracellular phase. The normal metabolic functioning of the cell is necessary to maintain the specificity of the adsorption sites. There is another intracellular phase, which lacks the structural specificity for K+, and which contains Na+, Cl-, and K+ in equilibrium with the external solution. The dimensions of the free intracellular phase will vary from cell to cell, but it will be smaller in the intact animal, and will increase on soaking in normal Ringer, until it is approximately one-third of the total cellular volume. The increase in this phase may be ascribed to a decrease in the energy available to maintain the ordered phase.

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