Regulatory Volume Decrease (RVD)

When cells are exposed to a decrease in osmolarity (hypotonic environment), there is an increase in cell
volume or hypo-osmotic cell swelling.
This volume increase is transient and is followed by a regulatory volume decrease (RVD). RVD is an
active process that involves the release of cations such as K+ and anions such as Cl- via activation of
separate K+ and Cl- channels or by activation of the K-Cl cotransporter. In a few cell types, K+ and Cl-
efflux is mediated by activation of K+/H+and Cl-/HCO3- exchangers. As these electrolytes are released
from the cell they bring with them obligated water in part by specialized water channels called
aquaporins (For review, see Verkman and Mitra, 2000, Agre et al., 2002). This net flux helps the cell
return to its original volume and establish a new osmotic equilibrium.
Finally, osmotic cell swelling also induces a rapid release of organic osmolytes such as taurine, alanine,
inositol through a yet unidentified volume sensitive organic osmolyte and anion channel (VSOAC) that
primarily transports Cl-. Since loss of inorganic osmolytes such as K+and Cl- can be potentially harmful
on a long-term basis, release of these electrolytes reverses with time, whereas the release of organic
osmolytes is more sustained (Olson, 1999). The efflux pattern of organic osmolytes also closely parallels
the time course of the change in cell volume, in contrast to Cl- and K+ fluxes which are faster (Cl-) or
slower (K+) than the change in cell volume (Pasantes-Morales, 1998) down regulation of the
mechanisms controlling synthesis and uptake of organic osmolytes also contributes to the loss of the
solutes. In many cases, exposure of cells to hypotonic media has been shown to cause a regulation of
the rates of both efflux and influx for a range of solutes. The net flux of organic osmolytes is usually out
of the cell (Lambert, 2004).