Cell volume regulatory mechanisms.

Prerequisites for cell survival include avoidance of excessive alterations of cell volume. Cells counterbalance the osmolarity due to cellular accumulation of organic substances by uneven distribution of inorganic ions. They extrude Na(+) in exchange for K(+) by the Na(+) /K(+) ATPase. The cell membrane is less permeable to Na(+) than to K(+) . The K(+) exit generates a cell-negative potential difference across the cell membrane which drives the exit of anions such as Cl(-) thus decreasing intracellular osmolarity. Upon cell swelling, cells release ions through activation of K(+) channels and/or anion channels, KCl-cotransport, or parallel activation of K(+) /H(+) exchange and Cl(-) /HCO-3 exchange. Upon cell shrinkage, cells accumulate ions through activation of Na(+) , K(+) , 2Cl(-) cotransport, Na(+) /H(+) exchange in parallel to Cl(-) /HCO3- exchange, or Na(+) channels. Na(+) taken up is extruded by the Na(+) /K(+) ATPase in exchange for K(+) . Shrunken cells further accumulate organic osmolytes. They generate sorbitol and glycerophosphorylcholine and monomeric amino acids by altered metabolism and take up myoinositol (inositol), betaine, taurine and amino acids by Na(+) coupled transport. They release osmolytes during cell swelling.