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Muscle and nerve possess two closely related properties that are of interest to the physiologist: a labile electric potential difference across the cell surface and the ability to accumulate selectively potassium from an environment poor in that cation but rich in sodium. It appears that most investigators primarily interested in the electric potential have adhered to the original concept laid down by Ostwald (1890), McDonald (1900), and Bernstein (1902) that the electric potential arises basically from a difference in permeabilities toward different ions. Such a differential ionic permeability, in turn, arises from the semipermeability of a unique cell membrane separating an intraeellular dilute solution of proteins and salts and the extracellular fluid, another dilute solution of similar composition. On the other hand, investigators in the field of ionic accumulation have been far from unanimous in accepting this membrane theory as an explanation of asymmetric ionic distribution. A large school of them have come to believe that the K + ion selectively accumulated in muscle and nerve cells for instance, is due to potassium ion binding within the cell (Neuschloss, 1926; Troschin, 1958~; Shaw and Simon, 1955; Menozzi et al., 1959). All in all, one can probably say that the proponents of the membrane theory have thus far presented a more persuasive set of arguments. For it has undoubtedly dominated the thinking in this field. A major weakness in the bound potassium concept lies in the general implication that "binding" is an irreversible process. Thus bound potassium was expected never to diffuse out of the cells even after the ceils are ground to a pulp. This expectation is simply not experimentally supported (see following discussion on K + ion binding of actomyosin). But even if one proposes a hypothesis including a labile reversible process there are other obstacles to overcome. Physiologists in their at tempt to understand living phenomena must draw upon well established physicochemical laws and models to explain the behavior of their less understood material. For the mechanism of electric po-

The Interpretation of Selective Ionic Permeability and Cellular Potentials in Terms of the Fixed Charge-Induction Hypothesis