Phospholipid flip-flop and the distribution of surface charges in excitable membranes

There is now good evidence that most of the lipids in a biological membrane are arranged in the form of a bilayer. Charged lipids in the membrane of an excitable cell are subject to a significant driving force, the gradient of the intramembrane potential, which will tend to redistribute the lipids between the two halves of the bilayer by a "phospholipid flip-flop" mechanism. We have calculated, by combining the Boltzmann relation from statistics and the Gouy equation from the theory of the diffuse double layer, the steady-state distribution of charged lipids in the bilayer. This distribution is completely determined, within the framework of the model, by three experimentally accessible variables; the percentage of charged lipid in the bilayer as a whole, the resting potential and the ionic strength. The known values for the percentage of anionic phospholipids in squid axons (10-15%), the membrane potential (50-100 mV) and ionic strength (0.5 M) imply that the charge density and double layer potential at the outer surface of the nerve will be substantially greater than the charge density and double layer potential at the inner surface, in agreement with the best available evidence from physiological measurements.