In recent years, it has become evident that the volume of a given cell is an important factor not only in defining its intracellular osmolality and its shape, but also in defining other cellular functions, such as transepithelial transport, cell migration, cell growth, cell death, and the regulation of intracellular metabolism. In addition, besides inorganic osmolytes, the existence of organic osmolytes in cells has been discovered. Osmolyte transport systems-channels and carriers alike-have been identified and characterized at a molecular level and also, to a certain extent, the intracellular signals regulating osmolyte movements across the plasma membrane. The current review reflects these developments and focuses on the contributions of inorganic and organic osmolytes and their transport systems in regulatory volume increase (RVI) and regulatory volume decrease (RVD) in a variety of cells. Furthermore, the current knowledge on signal transduction in volume regulation is compiled, revealing an astonishing diversity in transport systems, as well as of regulatory signals. The information available indicates the existence of intricate spatial and temporal networks that control cell volume and that we are just beginning to be able to investigate and to understand.

In confluent primary cultures of rat hepatocytes,hypertonic stress leads to cell shrinkage and activates non-selective cation channels as the main mechanism of regulatory cell volume increase. The process is found to employ the exocytotic insertion of channels into the plasma membrane and (in addition to PKC) PLC, tyrosine kinases and G proteins, but not PI 3-kinase are part of the signalling network. Furthermore, hypertonic stress leads to the formation of stress fibres and significantly alters the activity of RhoA, Rac and Cdc42. These latter effects, however, are likely to reflect the restoration of cell shape rather than the regulation of cell volume, both most probably converging at the level of focal adhesions and integrins.

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In confluent primary cultures of rat hepatocytes,hypertonic stress leads to cell shrinkage and activates non-selective cation channels as the main mechanism of regulatory cell volume increase. The process is found to employ the exocytotic insertion of channels into the plasma membrane and (in addition to PKC) PLC, tyrosine kinases and G proteins, but not PI 3-kinase are part of the signalling network. Furthermore, hypertonic stress leads to the formation of stress fibres and significantly alters the activity of RhoA, Rac and Cdc42. These latter effects, however, are likely to reflect the restoration of cell shape rather than the regulation of cell volume, both most probably converging at the level of focal adhesions and integrins.