The biological significance of cell volume.

To survive, cells have to avoid excessive alterations of their volume. To this end, cells have developed a complex machinery of cell volume regulatory mechanisms comprising transport across the cell membrane and metabolism. Upon cell swelling, they loose electrolytes mainly via selective K+ channels and unselective ion channels and/or KCl symport, upon cell shrinkage they accumulate ions by Na+,K+,2Cl- cotransport and parallel operation of Na+/H+ exchange and Cl-/HCO3- exchange. In addition, cell shrinkage stimulates glycogenolysis, proteolysis and formation of organic osmolytes such as amino acids, methylamines and polyols. Cell swelling stimulates formation of glycogen and proteins and cellular release of organic osmolytes. Alterations of cell volume do play a crucial role in the regulation of cell function, as illustrated by four examples: 1. Epithelial transport may lead to cell swelling, which then triggers volume regulatory mechanisms modifying transcellular transport. 2. Insulin swells hepatocytes by activation of Na+,K+,2Cl- cotransport and Na+/H+ exchange, glucagon shrinks those cells by activation of ion channels. The respective volume changes participate in the regulation of cellular protein and glycogen metabolism by these hormones. 3. Growth factors and expression of ras oncogene activate Na+,K+,2Cl- cotransport and Na+/H+ exchange, leading to the respective cell swelling. 4. Hepatocyte swelling triggers a hepatorenal reflex decreasing renal blood flow.