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.

Swelling-induced taurine release without chloride channel activity in Xenopus laevis oocytes expressing anion channels and transporters.

Taurine is an important osmolyte involved in cell volume regulation. During regulatory volume decrease it is released via a volume-sensitive organic osmolyte/anion channel. Several molecules have been suggested as candidates for osmolyte release. In this study, we chose three of these, namely ClC-2, ClC-3 and ICln, because of their expression in rat astrocytes, a cell type which is known to release taurine under hypotonic stress, and their activation by hypotonic shock. As all three candidates were also suggested to be chloride channels, we investigated their permeability for both chloride and taurine under isotonic and hypotonic conditions using the Xenopus laevis oocyte expression system. We found a volume-sensitive increase of chloride permeability in ClC-2-expressing oocytes only. Yet, the taurine permeability was significantly increased under hypotonic conditions in oocytes expressing any of the tested candidates. Further experiments confirmed that the detected taurine efflux does not represent unspecific leakage. These results suggest that ClC-2, ClC-3 and ICln either participate in taurine transport themselves or upregulate an endogenous oocyte osmolyte channel. In either case, the taurine efflux of oocytes not being accompanied by an increased chloride flux suggests that taurine and chloride can be released via two separate pathways.