Anion channels in a leaky epithelium

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

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Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death

Nature Cell Biology ◽

10.1038/ncb1575 ◽

2007 ◽

Vol 9 (5) ◽

pp. 550-555 ◽

Cited By ~ 645

Author(s):

Christopher P. Baines ◽

Robert A. Kaiser ◽

Tatiana Sheiko ◽

William J. Craigen ◽

Jeffery D. Molkentin

Keyword(s):

Cell Death ◽

Anion Channels ◽

Voltage Dependent ◽

Dependent Cell

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More than just a pressure relief valve: physiological roles of volume-regulated LRRC8 anion channels

Biological Chemistry ◽

10.1515/hsz-2019-0189 ◽

2019 ◽

Vol 400 (11) ◽

pp. 1481-1496 ◽

Cited By ~ 10

Author(s):

Lingye Chen ◽

Benjamin König ◽

Tianbao Liu ◽

Sumaira Pervaiz ◽

Yasmin S. Razzaque ◽

...

Keyword(s):

Volume Regulation ◽

Regulatory Volume Decrease ◽

Anion Channel ◽

Therapy Resistance ◽

Cell Swelling ◽

Organic Osmolytes ◽

Anion Channels ◽

Relief Valve ◽

Wide Range ◽

And Migration

Abstract The volume-regulated anion channel (VRAC) is a key player in the volume regulation of vertebrate cells. This ubiquitously expressed channel opens upon osmotic cell swelling and potentially other cues and releases chloride and organic osmolytes, which contributes to regulatory volume decrease (RVD). A plethora of studies have proposed a wide range of physiological roles for VRAC beyond volume regulation including cell proliferation, differentiation and migration, apoptosis, intercellular communication by direct release of signaling molecules and by supporting the exocytosis of insulin. VRAC was additionally implicated in pathological states such as cancer therapy resistance and excitotoxicity under ischemic conditions. Following extensive investigations, 5 years ago leucine-rich repeat-containing family 8 (LRRC8) heteromers containing LRRC8A were identified as the pore-forming components of VRAC. Since then, molecular biological approaches have allowed further insight into the biophysical properties and structure of VRAC. Heterologous expression, siRNA-mediated downregulation and genome editing in cells, as well as the use of animal models have enabled the assessment of the proposed physiological roles, together with the identification of new functions including spermatogenesis and the uptake of antibiotics and platinum-based cancer drugs. This review discusses the recent molecular biological insights into the physiology of VRAC in relation to its previously proposed roles.

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Glutamate Transporter-Associated Anion Channels

Biophysical Journal ◽

10.1016/j.bpj.2011.11.2227 ◽

2012 ◽

Vol 102 (3) ◽

pp. 407a

Author(s):

Christoph Fahlke

Keyword(s):

Glutamate Transporter ◽

Anion Channels

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Modulation of frequency and height of cytosolic calcium spikes by plasma membrane anion channels in guard cells

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab118 ◽

2021 ◽

Author(s):

Md Tahjib-Ul-Arif ◽

Shintaro Munemasa ◽

Toshiyuki Nakamura ◽

Yoshimasa Nakamura ◽

Yoshiyuki Murata

Keyword(s):

Plasma Membrane ◽

Stomatal Closure ◽

Anion Channel ◽

Guard Cells ◽

Cytosolic Calcium ◽

Peak Height ◽

Extracellular Calcium ◽

Wild Type ◽

Anion Channels ◽

In The Wild

Abstract Cytosolic calcium ([Ca2+]cyt) elevation activates plasma membrane anion channels in guard cells, which is required for stomatal closure. However, involvement of the anion channels in the [Ca2+]cyt elevation remains unclear. We investigated the involvement using Arabidopsis thaliana anion channel mutants, slac1-4 slah3-3 and slac1-4 almt12-1. Extracellular calcium induced stomatal closure in the wild-type plants but not in the anion channel mutant plants whereas extracellular calcium induced [Ca2+]cyt elevation both in the wild-type guard cells and in the mutant guard cells. The peak height and the number of the [Ca2+]cyt spike were lower and larger in the slac1-4 slah3-3 than in the wild-type and the height and the number in the slac1-4 almt12-1 were much lower and much larger than in the wild-type. These results suggest that the anion channels are involved in the regulation of [Ca2+]cyt elevation in guard cells.

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Claudin-2 is selectively expressed in proximal nephron in mouse kidney

AJP Renal Physiology ◽

10.1152/ajprenal.0021.2001 ◽

2001 ◽

Vol 281 (5) ◽

pp. F966-F974 ◽

Cited By ~ 97

Author(s):

Alissa H. Enck ◽

Urs V. Berger ◽

Alan S. L. Yu

Keyword(s):

Tight Junction ◽

Large Family ◽

Mouse Kidney ◽

High Rate ◽

Structural Components ◽

Water Reabsorption ◽

Junction Protein ◽

Confocal Images ◽

Leaky Epithelium

First published August 15, 2001; 10.1152/ajprenal.00021.2001.—The proximal nephron possesses a leaky epithelium with unique paracellular permeability properties that underlie its high rate of passive NaCl and water reabsorption, but the molecular basis is unknown. The claudins are a large family of transmembrane proteins that are part of the tight junction complex and likely form structural components of a paracellular pore. To localize claudin-2 in the mouse kidney, we performed in situ hybridization using an isoform-specific riboprobe and immunohistochemistry using a polyclonal antibody directed against a COOH-terminal peptide. Claudin-2 mRNA and protein were found throughout the proximal tubule and in the contiguous early segment of the thin descending limb of long-looped nephrons. The level of expression demonstrated an axial increase from proximal to distal segments. In confocal images, the subcellular localization of claudin-2 protein coincided with that of the tight junction protein ZO-1. Our findings suggest that claudin-2 is a component of the paracellular pathway of the most proximal segments of the nephron and that it may be responsible for their uniquely leaky permeability properties.

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Voltage-dependent block of endothelial volume-regulated anion channels by calix[4]arenes

AJP Cell Physiology ◽

10.1152/ajpcell.1998.275.3.c646 ◽

1998 ◽

Vol 275 (3) ◽

pp. C646-C652 ◽

Cited By ~ 34

Author(s):

Guy Droogmans ◽

Jean Prenen ◽

Jan Eggermont ◽

Thomas Voets ◽

Bernd Nilius

Keyword(s):

Open Channel ◽

Single Channel ◽

Anion Channel ◽

Anion Channels ◽

Channel Conductance ◽

Open Channel Block ◽

Maximum Inhibition ◽

Voltage Dependent ◽

A Site ◽

Maximal Block

We have studied the effects of calix[4]arenes on the volume-regulated anion channel (VRAC) currents in cultured calf pulmonary artery endothelial cells. TS- and TS-TM-calix[4]arenes induced a fast inhibition at positive potentials but were ineffective at negative potentials. Maximal block occurred at potentials between 30 and 50 mV. Lowering extracellular pH enhanced the block and shifted the maximum inhibition to more negative potentials. Current inhibition was also accompanied by an increased current noise. From the analysis of the calix[4]arene-induced noise, we obtained a single-channel conductance of 9.3 ± 2.1 pS ( n = 9) at +30 mV. The voltage- and time-dependent block were described using a model in which calix[4]arenes bind to a site at an electrical distance of 0.25 inside the channel with an affinity of 220 μM at 0 mV. Binding occludes VRAC at moderately positive potentials, but calix[4]arenes permeate the channel at more positive potentials. In conclusion, our data suggest an open-channel block of VRAC by calix[4]arenes that also depends on the protonation of the binding site within the pore.

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