Sulphonic acid derivatives as probes of pore properties of volume‐regulated anion channels in endothelial cells

Droogmans, Guillaume; Maertens, Chantal; Prenen, Jean; Nilius, Bernd

doi:10.1038/sj.bjp.0702770

Cited by 59 publications

(49 citation statements)

References 10 publications

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“…The relief of the blocking effect at very positive potentials is however only observed for compounds small enough to permeate the pore. Calix[6]arene and calix [8]arene are apparently not able to permeate the VRAC pore, from which a pore diameter between 1 and 1.6 nm has been estimated, a value in the same range as the values obtained above [33,34].…”

Section: Pharmacologysupporting

confidence: 64%

The Endothelial Volume-Regulated Anion Channel, VRAC

Nilius

Eggermont

Droogmans³

2000

Cell Physiol Biochem

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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.

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Section: Pharmacologysupporting

confidence: 64%

The Endothelial Volume-Regulated Anion Channel, VRAC

Nilius

Eggermont

Droogmans³

2000

Cell Physiol Biochem

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“…Because the swellinginduced Cl Ϫ current through VRAC (I Cl,swell ) and the swelling-induced release of organic osmolytes share several characteristics in terms of pharmacology, kinetics, and activation parameters, it has been proposed that VRAC also functions as a pathway for organic osmolytes such as taurine, D-myo-inositol, and sorbitol (13). The estimated pore diameter of VRAC (ϳ1.1 nm) is indeed compatible with permeability for taurine and polyols (9,26). For this reason, VRAC is sometimes referred to as the volume-sensitive organic osmolyte anion channel.…”

mentioning

confidence: 53%

Stimulation by caveolin-1 of the hypotonicity-induced release of taurine and ATP at basolateral, but not apical, membrane of Caco-2 cells

Ullrich

Caplanusi²,

Brône³

et al. 2006

American Journal of Physiology-Cell Physiology

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germont. Stimulation by caveolin-1 of the hypotonicity-induced release of taurine and ATP at basolateral, but not apical, membrane of Caco-2 cells. Am J Physiol Cell Physiol 290: C1287-C1296, 2006. First published December 7, 2005 doi:10.1152/ajpcell.00545.2005.-Regulatory volume decrease (RVD) is a protective mechanism that allows mammalian cells to restore their volume when exposed to a hypotonic environment. A key component of RVD is the release of K ϩ , Cl Ϫ , and organic osmolytes, such as taurine, which then drives osmotic water efflux. Previous experiments have indicated that caveolin-1, a coat protein of caveolae microdomains in the plasma membrane, promotes the swelling-induced Cl Ϫ current (ICl,swell) through volume-regulated anion channels. However, it is not known whether the stimulation by caveolin-1 is restricted to the release of Cl Ϫ or whether it also affects the swelling-induced release of other components, such as organic osmolytes. To address this problem, we have studied I Cl,swell and the hypotonicity-induced release of taurine and ATP in wild-type Caco-2 cells that are caveolin-1 deficient and in stably transfected Caco-2 cells that express caveolin-1. Electrophysiological characterization of wild-type and stably transfected Caco-2 showed that caveolin-1 promoted I Cl,swell, but not cystic fibrosis transmembrane conductance regulator currents. Furthermore, caveolin-1 expression stimulated the hypotonicity-induced release of taurine and ATP in stably transfected Caco-2 cells grown as a monolayer. Interestingly, the effect of caveolin-1 was polarized because only the release at the basolateral membrane, but not at the apical membrane, was increased. It is therefore concluded that caveolin-1 facilitates the hypotonicity-induced release of Cl Ϫ , taurine, and ATP, and that in polarized epithelial cells, the effect of caveolin-1 is compartmentalized to the basolateral membrane. caveolae; osmolyte; epithelial cell; chloride channel WHEN EXPOSED TO AN ACUTE hypotonic stimulus (HTS), mammalian cells typically release K ϩ , Cl Ϫ , and organic osmolytes, such as taurine, D-myo-inositol, and sorbitol, in an attempt to counteract the volume increase and to avoid swelling-induced cell lysis (27,33,51). The cellular loss of osmolytes drives the osmotic efflux of water, thereby restoring (partially) the initial cell volume, a phenomenon also known as regulatory volume decrease (RVD). In some cell types (e.g., astrocytes, airway and intestinal epithelial cells, and pancreatic acinar cells), hypotonic swelling also provokes the release of ATP, which has been proposed to assist RVD in an autocrine/paracrine way (7,8,21,39).The ion channel that is responsible for the swelling-induced release of Cl Ϫ is known as the volume-regulated anion channel (VRAC) (also known as volume-sensitive organic osmolyteanion channel or volume-sensitive outwardly rectifying channel). VRAC is a ubiquitously expressed plasma membrane anion-selective channel that has been extensively characterized at the biophysical and pharmacolo...

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“…Instead, the Cl Ϫ current in these cells displayed two components. The first was a current with biophysical and pharmacological properties like VRAC, a cell volume-activated anion current (40,41) that is very different from the outward rectifying, slowly developing CaCC current found in salivary gland acinar cells (15,18). The second Cl Ϫ current was activated at negative potentials in a time-dependent and NFA-insensitive manner, reminiscent of the inward rectifying Cl Ϫ current in mouse submandibular duct cells that is inhibited by cadmium and is absent in ClC-2 null mice (37).…”

Section: Ca 2ϩmentioning

confidence: 99%

“…weak outward rectification and slow inactivation at positive potentials) and pharmacological properties like VRAC, the volume-activated anion current (40,41). Recording of CaCC current was performed only in the absence of VRAC as evidenced by the lack of both voltage-dependent inactivation at positive potentials and sensitivity of the current to 100 M suramin (40).…”

Section: Heterologous Expression Of Mousementioning

confidence: 99%