Comparative physiology of cellular ion and volume regulation.

1. Intracellular [K+]i in most cells is around 100-150 mOs. This is true in invertebrate or vertebrate muscle or any other tissue, and the only known exceptions being the axons of some invertebrates (Burton, '73). 2. When cell volume is increased due to hypoosmotic swelling, cell volume is regulated back toward normal in almost all cells. In cells with an osmolality of 300-350 mOs, the regulatory volume decrease is caused primarily by a passive efflux of potassium and anions due to increased membrane permeability to potassium. In cells with a higher osmolality, regulatory volume decrease is caused by the passive efflux of small organic molecules. 3. When cell volume is decreased due to hyperosmotic shrinking, volume is not always regulated back toward normal in in vitro experiments carried out for several hours. However, it appears from the in vivo experiments that some cell volume control is always present. The volume control in the flounder red cells took place through increased sodium influx brought about by a relative increase in cell membrane permeability to sodium. This mechanism also appears to be dominant in the mammalian renal papilla, where the [Na+]i increases in proportion to the increase in cellular osmolality with no change in [K+]i. 4. Cells which remain shrunken in vitro, or cells which only partly restore their volume in vivo, do not exhibit increased [K+]i. This finding means that potassium is lost from the cell and, in most cases, exchanged for sodium when the volume is decreased, even though the osmotic concentration in the extracellular fluid is elevated. 5. Finally, it appears that the maintenance of a rather constant [K+]i is important for all cells. This constancy may be due to the fact that certain enzymes are sensitive to the intracellular potassium concentration. Thus, the DNA synthesis is blocked in mammalian kidney cells when [K+]i is increased (Bygrave, '67). Furthermore, Lubin ('64) has shown that low [K+]i concentrations also cause a decrease in DNA, RNA, and protein synthesis. An optimal concentration appears to be necessary for protein synthesis.