Abstract
Proteins in any solution with a pH value that differs from their isoelectric point exert both an electric Donnan effect (DE) and colloid osmotic pressure. While the former alters the distribution of ions, the latter forces water diffusion. In cells with highly Cl--permeable membranes, the resting potential is more dependent on the cytoplasmic pH value, which alters the Donnan effect of cell proteins, than on the current action of Na/K pumps. Any weak (positive or negative) electric disturbances of their resting potential are quickly corrected by chloride shifts.In many excitable cells, the spreading of action potentials is mediated through fast, voltage-gated sodium channels. Tissue cells share similar concentrations of cytoplasmic proteins and almost the same exposure to the interstitial fluid (IF) chloride concentration. The consequence is that similar intra- and extra-cellular chloride concentrations make these cells share the same Nernst value for Cl-.Further extrapolation indicates that cells with the same chloride Nernst value and high chloride permeability should have similar resting membrane potentials, more negative than -80 mV. Fast sodium channels require potassium levels >20 times higher inside the cell than around it, while the concentration of Cl- ions needs to be >20 times higher outside the cell.When osmotic forces, electroneutrality and other ions are all taken into account, the overall osmolarity needs to be near 280 to 300 mosm/L to reach the required resting potential in excitable cells. High plasma protein concentrations keep the IF chloride concentration stable, which is important in keeping the resting membrane potential similar in all chloride-permeable cells. Probable consequences of this concept for neuron excitability, erythrocyte membrane permeability and several features of circulation design are briefly discussed.
Highlights
This theoretical paper seeks to interpret similarities in pH, electrolyte and protein compositions of body fluids among diverse animals as requirements imposed by their excitable tissues, neurons and muscle cells.The logic that follows is based on a previously published argument that similar body fluid osmolarity in various animals is dictated by the opposed Donnan effects of cell proteins and of sodium ions sequestered in the extracellular fluid (ECF) [1]
The conclusion of the cited paper is that the ubiquitous ECF Na+ concentration is determined by the average osmotic burden on animal tissue cells
The first is the electric Donnan effect (DE), which alters the distribution of ions, and the second is the colloid osmotic pressure, which forces water diffusion
Summary
This theoretical paper seeks to interpret similarities in pH, electrolyte and protein compositions of body fluids among diverse animals as requirements imposed by their excitable tissues, neurons and muscle cells. When the three main body fluid compartments - plasma, interstitial (IF) and cellular fluid - are considered, differences in chloride distribution across cell membranes and capillary walls result not from chloride pumping, but from the Donnan effect of cytoplasmic and plasma proteins [4] Both cellular and plasma proteins force negative chloride ions to enter the protein-poor IF. Two opposed Donnan effects result in higher intracellular chloride concentrations, as has been reported in blood cells that normally float in protein-rich plasma [2] In these cells, sodium pumping is less important for maintaining the cell volume, since the osmotic burden is already reduced by the DE of the plasma proteins. High plasma protein levels maintain the stability of the IF chloride concentration through their Donnan effect, important in keeping the resting membrane potential similar in all chloride-permeable cells. A4: High Cl- permeability dampens small changes in membrane potential, preventing depolarization or hyperpolarization
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