Abstract
Cellular swelling is controlled by an active mechanism of cell volume regulation driven by a Na+/K+-dependent ATPase and by aquaporins which translocate water along the osmotic gradient. Na+/K+-pump may be blocked by ouabain, a digitalic derivative, by inhibition of ATP, or by drastic ion alterations of extracellular fluid. However, it has been observed that some tissues are still able to control their volume despite the presence of ouabain, suggesting the existence of other mechanisms of cell volume control. In 1977, by correlating electron microscopy observation with ion and water composition of liver slices incubated in different metabolic conditions in the presence or absence of ouabain, we observed that hepatocytes were able to control their volume extruding water and recovering ion composition in the presence of ouabain. In particular, hepatocytes were able to sequester ions and water in intracellular vesicles and then secrete them at the bile canaliculus pole. We named this “vesicular mechanism of cell volume control.” Afterward, this mechanism has been confirmed by us and other laboratories in several mammalian tissues. This review summarizes evidences regarding this mechanism, problems that are still pending, and questions that need to be answered. Finally, we shortly review the importance of cell volume control in some human pathological conditions.
Highlights
Cellular swelling is controlled by an active mechanism of cell volume regulation driven by a Na+/K+-dependent ATPase and by aquaporins which translocate water along the osmotic gradient
In 1977, by correlating electron microscopy observation with ion and water composition of liver slices incubated in different metabolic conditions in the presence or absence of ouabain, we observed that hepatocytes were able to control their volume extruding water and recovering ion composition in the presence of ouabain
Water movements may be transcellular, paracellular, or intracellular: transcellular transport occurs at the level of basal or apical pole of a cell to extrude or reabsorb water, paracellular transport or exchange occurs at lateral surface of cells through junctional complexes, especially tight junctions, and intracellular water movements are responsible for water distribution among various subcellular compartments (i.e., from cytosol and nucleoplasm to various cisternae or to mitochondrial matrix), implying the presence of APQs in each subcompartment of cell membranes involved in water transport
Summary
“Cloudy swelling” is an early and frequent morphological cell alteration first identified by Virchow in his “Die Cellular Pathologie” [1]. A clear picture of the underlying pathogenetic mechanisms of cell swelling is important to understand many aspects of human diseases Living cells regulate their water content even under apparently isosmotic conditions to compensate the osmotic forces due to higher intracellular concentration of charged macromolecules [3]. By using different in vitro models, Wilson [4], Leaf [5], and Macknight and Leaf [3] demonstrated the role of active transport of ions across the BioMed Research International plasma membrane in preventing swelling under isosmotic condition They showed that the distribution of Na+ was crucial and that its physiologic concentrations were maintained by a coupled transport of Na+ and K+, operated by a Na+/K+ATPase, a pump apparently totally inhibited by ouabain both in in vitro and in soluble systems. This review aims to summarize evidences that we have at present about cellular swelling, problems that are still pending, and questions that need an answer
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