Quantitative molecular approach to the permeability changes of excitation

Functional relationships, available from only a few monolayer studies, can be applied to a relatively simple model of the excitable membrane to give permeability-potential curves quite similar to the conductance-potential curves obtained experimentally in voltage-clamped giant axons. Contrary to the usual view in terms of "carrier systems," the present model considers the permeability to sodium and potassium to be reduced by the increase in the surface pressure induced by large lipophilic cations and anions in the outer layer of the lipoidal bimolecular leaflet constituting the living membrane; hence, the increase in permeability during depolarization, for example, is due to a decrease in the amount of the organic anions in this layer, whereas the decrease in sodium permeability during inactivation is caused by a rise in content of organic cations. The present proposal has the advantage that it is in keeping with known phenomena observed in simple physico-chemical systems as well as in excitable systems; moreover, the current actually transferred by the postulated lipophilic ions can be negligible compared to that transferred by the inorganic cations they control. The latter situation, as well as the steepness of the permeability-potential relationships obtained, have been pointed out to be critical requirements of a satisfactory molecular hypothesis.