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J Theor Biol. 2008 Jun 21;252(4):769-72. doi: 10.1016/j.jtbi.2008.02.022. Epub 2008 Feb 23.

Are extracellular osmolality and sodium concentration determined by Donnan effects of intracellular protein charges and of pumped sodium?

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Department of Physiology, Osijek Medical Faculty, J Huttlera 4, 31000 Osijek, Croatia.


Although we are used to attribute almost identical extracellular fluid (ECF) sodium concentrations in birds, amphibians, reptiles, and mammals to the composition of the primordial oceans in which, presumably, all life originated, this interpretation is not supported by geological data suggesting that the ocean salinity was never much lower than the present-day values, still four times higher than our plasma sodium. Here presented interpretation is that the similar ECF salt concentrations are dictated by the opposed Donnan effects on the cell membrane. The only way for the cell to reach the osmotic equilibrium is to alter cell volume, until concentration of nondiffusible intracellular ions (mainly charges on intracellular proteins) is equal to the ECF restricted ions (mainly Na+ ions, restricted by pumping out of cells). The achievement of electroneutrality requires that the sum of all anions equals concentration of positive ions in the cell (mainly K+). Negative charges on cytoplasmic proteins are the most stable component among ionized particles and other ions have to adapt to their concentration. Positive and negative soluble intracellular ions are all osmotically active and to achieve balance of osmotic forces on the cell membrane, the sum of their intracellular concentrations must equal the concentration of osmotically active extracellular particles. Since almost half the osmotically active ECF particles are sodium ions, the ECF sodium concentration seems related to concentration of charges on cytoplasmic proteins and concentration of intracellular phosphates. Our ancestors could not leave the salty ocean and move to brackish, or even fresh waters, without adequate regulation of their ECF sodium concentration and osmolality. Concentration of charges on cytoplasmic proteins or of intracellular phosphate buffers could not be altered, since this would compromise cell functioning. The remaining solution was to maintain the lowest ECF Na+ concentration effective in counteracting the average Donnan effect of charges on cytoplasmic proteins. When the optimal ECF sodium concentration had once become the reference point for osmoreceptors (controlling thirst and ADH secretion) and other regulatory mechanisms (secretion of renin/angiotensin/aldosterone, natriuretic factors), it made an important survival advantage that allowed spreading of animal life in fresh water and conquering of earth. The actual common value had to be a compromise that reduces the average osmotic burden on body cells to zero. Individual cells can reduce eventual residual osmotic forces on their membrane through altering cell volume by chloride shift, and by modulating the Na+K+-ATPase function.

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