The resting membrane potential of cells are measures of electrical work, not of ionic currents.

Living cells create electric potential force, E, between their various phases by at least three distinct mechanisms. Charge separation, F = [equation: see text] (Eqn 1) creates the potential, E = [equation: see text] of -120 to -145 mV between cytoplasmic and mitochondrial phases by unbalanced proton expulsion powered by the redox energy of the respiratory chain. Electrically unbalanced flow of Na+ through voltage gated Na+ channels raises the potential of nerve from -85 to +30 mV. The so-called resting potential of cells, which varies from -85 mV in heart to -4.5 mV in red cell, does not appear to result from the unbalanced flow of ions between phases, but rather to be a measure of the work required to move ions between phases. Movement of an ion between phases entails three types of energy. Concentration work is that required to move an ion between phases containing different concentrations of ions: [equation: see text] Electrical work is that work required to move an ion from phases with differing electric potentials: [equation: see text] The Nernst potential of an ion existing at different concentrations in two phases is: [equation: see text] The osmotic work term is small and can generally be ignored. In heart the measured resting potential between extra- and intracellular phases, EN is approximately -85 mV. The calculated Nernst potential of K+, E [K+]out/in, is -85 mV (Eqn 4). This means that in heart, K+ distributes itself between the two phases as if it moved through an open ion channel. Its concentration work (Eqn 2) is equal in magnitude but opposite in sign to its electrical work (Eqn 3). This makes net K+ current flow, I, equal 0, indicating that this potential cannot be a diffusion potential. In liver the resting potential ranges from -28 to -40 mV, and is equivalent to the E[Cl-]out/in, while in red cell the resting potential is about -4.5 mV, which is equivalent to the potential of all nine major inorganic ion species except Na+, K+ and Ca2+. Therefore the resting potential between extra- and intracellular phases of cells should be thought of, not as a diffusion potential but rather as a measure of the electrical work: [equation: see text] required to transport the most permeant ions in a Gibbs-Donnan near-equilibrium system, either K+ or Cl- or both, between the phases of an aqueous system during the flow of current required to measure potentials with intracellular KCl electrodes or during ion movements brought about during normal cellular activity. The resting electrical potential results from the existence of a mono-ionic Gibbs-Donnan near-equilibrium system between the extra- and intracellular phases of cell wherein the activity of free H2O within all phases of the system is equal and the energy of the gradients of the nine major inorganic ions, delta G[ionz]out/in, are in near-equilibrium with one another, with the potential between the phases, EN, and with the energy of ATP hydrolysis. delta GATP Hydrolysis. ranges from a low of -55 to slightly over -60 kJ/mole in all cell types.(ABSTRACT TRUNCATED AT 400 WORDS)