IS THE RESTING POTENTIAL OF RANVIER NODES A POTASSIUM POTENTIAL? *

The membrane theory of Julius Bernstein (1902) assumes that the potential difference (PD) existing between the interior of muscle or nerve cells and the extracellular fluid is caused by the concentration gradient of potassium if the membrane separating the two media is selectively permeable to potassium rather than to chloride and sodium ions. Owing to the high intracellular potassium concentration, the resting membrane of these excitable structures would then be continuously polarized, and the inside would be negative with respect to the extracellular fluid. This would agree with the observation that injured parts of nerve or muscle are negative compared to uninjured regions of the same structure. Bernstein based this theory on thermodynamics, proving that within reasonable limits the injury potential of nerve and muscle varied in proportion to the absolute temperature, thus presenting the characteristics of a concentration cell. Ever since his report efforts have been made to prove or to disprove Bernstein's hypothesis. The most striking evidence in favor of it was obtained by changing the extracellular potassium concentration [K], and finding a linear relationship between membrane potential (V,) and log [K],. , a t least if [KIe was varied between 10 and 60 times the normal potassium content of extracellular fluids. Such experiments were performed on different species and different excitable cells: by Curtis and Cole (1942) on giant nerve fibers of the squid; by Ling and Gerard (1950) and Adrian (1956) on striated frog muscle fibers; and by Huxley and the author (1951b) on single myelinated frog nerve fibers. The results showed clearly for all these excitable structures that the curve relating V, with log [K], approaches a straight line with a slope of 58-mV potential change for a tenfold increase of [KIc within the range of concentrations already mentioned. This behavior fits the Nernst equation for a potassium concentration cell, where V, = 58 log ([KIJK],) mV a t 20" C. , [K]i representing the potassium concentration of the cell plasma. The deviation of the experimental curve from the theoretical straight line and the flattening out of the curve at low [K], was explained by permeabilities of the membrane to other ions, such as C1and Na+ which, although smaller than the potassium permeability, are not negligible and will prevent an increase of V,,, to infinity a t low [Kl0. Furthermore, Hodgkin and Katz (1949), basing on the constant field theory of Goldman (1943), obtained an equation fitting the experimental values quite well if the relative values for the permeability coefficients for K+, Naf, and C1were chosen appropriately. Everything seemed consistent with the original view of Bernstein as far as the resting potential (RP) was concerned, and there was general agreement among physiologists that the R P is a PD of a potassium concentration cell, somewhat modified by a small but not negligible * The work reported in this paper was supported in part by grants from the Deutsche Forschungsgemeinschaft, Bad Godesberg, Germany, and from the Schweizerische Nationalfonds zur Forderung der wissenschaftlichen Forschung, Bern, and the Sandoz-Stiftung, Basel, Switzerland.