The Endothelial Volume-Regulated Anion Channel, VRAC

Abstract

We discuss in this short review properties of a volume-regulated anion channel that we have described in vascular endothelial cells. This channel, VRAC (volume-regulated anion channel) is outwardly rectifying with single channel conductances between 10-20pS for inward currents and 40-50pS for outward currents. VRAC is permeable for a wide range of anions, amino acids and organic osmolytes. The estimated pore diameter is approximately 1.1nm. VRAC is gated by a probably complex mechanism in which changes in ionic strength, tyrosine phosphorylation, the cytoskeletal organiser RhoA and possibly caveolin are essentially involved. The molecular candidate for this channel is still elusive. The functional impact of VRAC as a possible mechano-sensor in endothelium and as a regulatory component in the cell cycle, endothelial cell proliferation and possible angiogenesis will be discussed.

Hypertonicity Sensing in Organum Vasculosum Lamina Terminalis Neurons: A Mechanical Process InvolvingTRPV1But NotTRPV4

“…Although these findings indicated that extraction of cellular water is a requirement for hypertonicity sensing, they did not reveal whether this process specifically requires shrinking or a concentration of solutes in the cytoplasm. Indeed, recent work has shown that many types of ion channels can be modulated by changes in ionic strength (Nilius et al, 2000) or by the concentration of intracellular solutes such as Ca 2ϩ , phosphoinositides, or cyclic nucleotides (Cukkemane et al, 2011). Moreover, many types of cells are endowed with mechanisms that allow cell volume to recover within seconds after the onset of osmotic shrinking (Strange, 2004;Lang, 2007), an effect that could limit the usefulness of shrinking as an osmosensing signal.…”

“…Acute extracellular hypertonicity causes water efflux from cells to equalize osmotic forces and therefore provokes increases in intracellular solute concentration and decreases in cell volume. Since many types of ion channels are regulated by specific solutes (e.g., Cukkemane et al, 2011) or ionic strength (e.g., Nilius et al, 2000), osmosensing could in principle be mediated by osmotically induced changes in solute concentration. Alternately, OVLT neurons might detect hypertonicity through a mechanical effect linked to shrinking, as observed in neurohypophysial neurons of the supraoptic nucleus (Zhang et al, 2007).…”

Leflunomide Prevents Alveolar Fluid Clearance Inhibition by Respiratory Syncytial Virus

“…Although no specific VRAC inhibitors exist, these channels can be blocked by a variety of pharmacologic agents that, individually, have pleiotropic effects on other cellular systems (reviewed in Nilius and coworkers [23]). RSV-mediated inhibition of AFC on Day 2 was blocked by addition to the AFC instillate of each of several structurally unrelated VRAC inhibitors, but not by inhibitors of cystic fibrosis transmembrane regulator (24) or Ca 2ϩ -activated Cl -channel (25) activity (Table 4).…”

Hypotonicity induced K+ and anion conductive pathways activation in eel intestinal epithelium

“…The (Hoffmann 1978;Busch and Maylie, 1993;Deutsch and Chen, 1993;Felipe et al, 1993;Hoffmann and Dunham, 1995;Fürst et al, 2000;Hoffmann, 2000;Niemeyer et al, 2000;Nilius et al, 2000;Strange et al, 1996;Okada, 1997;Valverde et al, 2000). Electroneutral K + -Cl -cotransporter is an alternative system contributing to RVD in some cell types (Lauf and Adragna, 2000).…”