Origin and magnitude of transmembrane resting potential in living cells

Abstract

The equations of Nernst, Teorell, Ussing and Goldman do not explain the origin of cell membrane potential. The Nernst equation is concerned with equilibria and applies to the Donnan system, whereas living cells are much more complicated. Equations of Teorell and Ussing provide criteria for active transport but cannot predict cell membrane potential from starting conditions. The Goldman equation describes a membrane diffusion potential, and is useful in predicting transient changes in a pre-existing membrane potential, elicited by manipulation of ion permeabilities or external ion concentrations. However, none of these equations can predict both membrane potential and internal ion concentrations; they always predict one using the other with external concentration data, and yet both are determined by metabolic activity. When it exists in a steady state, in some cases membrane potential is wrongly described as a diffusion potential. An electrochemical analysis has been applied to models designed to represent the cell and equations have been derived for membrane potential. Starting conditions imposed were external ion concentrations, the existence in the membrane of active transport pumps and the presence in the cell of Donnan macro-ions. The effect of macro-ions outside was also considered. This study established that membrane potential can be successfully predicted from those starting conditions in all cell types examined, in blood plasma, fresh water and sea water. Several new effects were revealed, perhaps the most important of which was a ‘ nebenion effect ', the depressive effect on membrane potential of diffusible ions of the same charge sign as the pumped ion. This discovery has far-reaching consequences, for instance, that transport of hydrogen or hydroxyl ions at a membrane can never in itself develop a significant potential difference across the membrane, even though high pH gradients may be achieved. Other effects discovered were: a ‘ Donnan enhancement effect ’, whereby membrane potential can be much more than the sum of Donnan potential and transport-generated potential when both exist together; virtual lack of a ‘ double Donnan effect '; external macro-ion does not abolish the Donnan enhancement effect even when no Donnan potential would appear in the absence of active transport; a ‘ linked transport effect ’, allowing calculation of the potassium equilibrium potential; and a ‘ twin independent transport effect ’, in which the membrane potential falls short of the sum of each independent transport acting alone.