Organic Osmolyte Channels: A Comparative View

Abstract

Cells respond to osmotic swelling by releasing inorganic ions and small organic molecules (organic osmolytes). In many cell-types, osmotic swelling results in the activation of an outwardly-rectifying anion-selective current. The channel underlying this current has a significant permeability to a number of organic osmolytes and may play a role in the hypoosmotically-activated efflux of these compounds. However, there is also evidence that the volume-regulatory efflux of organic osmolytes involves other pathways which may be selective for neutral osmolytes over anions.

ATP regulates anion channel-mediated organic osmolyte release from cultured rat astrocytes via multiple Ca2+-sensitive mechanisms

“…We cannot exclude the possibility, however, that other transport systems may provide a minor contribution to D-[ 3 H]aspartate fluxes measured in our experiments or that more than one VRAC-like permeability pathway may exist in cultured astrocytes (26,47).…”

“…Ubiquitously expressed volume-regulated anion channels (VRACs) are permeable to a variety of inorganic anions, small organic anions, and uncharged molecules, including the amino acids taurine, glutamate, and aspartate (30,49,51,71). Although the molecular identity of VRACs has not been established, there is good evidence that, at least in some cell types, more than one type of anion channel may contribute to swelling-activated Cl Ϫ and organic osmolyte fluxes (2,26,31,78). In addition to their role in cell volume homeostasis, VRACs are also thought to participate in a variety of other processes including cell proliferation, apoptosis, and mechanosensitivity in endothelial and muscle cells (13,52).…”

Cell volume regulation: osmolytes, osmolyte transport, and signal transduction

“…In recent years it has become, however, more and more evident that-similar to other phyla in nature-in mammalian cells also organic osmolytes are employed in volume regulation (Yancey et al 1982;Hoffmann et al 1988;Kinne 1993;Burg 1995;Burg 1996;Junankar and Kirk 2000).…”

“…Taurine efflux is passive and directed only by the concentration difference Roy and Malo 1992), lacks saturability and transstimulation. In addition, taurine flux in a variety of cells is inhibited by a range of anion channel blockers (Goldstein and Davis 1994;Boese et al 1996b;Goldstein et al 1996;Hall et al 1996;Kinne et al 1996;Junankar and Kirk 2000). These properties suggest that taurine efflux is mediated by a transport system which is more similar to a channel than to a transporter (Kirk 1997;Kirk and Strange 1998;Perlman and Goldstein 1999;Shen et al 2002).…”

Osmotic Swelling Activates two Pathways for K⁺ Efflux in a Rat Hepatoma Cell Line

“…There is evidence from a wide variety of cell types that the swelling-activated transport of anions, a range of structurally unrelated organic osmolytes, and some cations, can occur through a common pathway [17][18][19][20][21]. However there is also evidence from a number of studies that the swelling-activated efflux of taurine and inorganic anions is mediated by separate pathways [22][23][24].…”