Piezo1 controls cell volume and migration by modulating swelling‐activated chloride current through Ca 2+ influx

Author(s):  
Luigi Sforna ◽  
Antonio Michelucci ◽  
Francesco Morena ◽  
Chiara Argentati ◽  
Fabio Franciolini ◽  
...  
2004 ◽  
Vol 54 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Shintaro Yamamoto ◽  
Keiko Ishihara ◽  
Tsuguhisa Ehara ◽  
Takao Shioya

2018 ◽  
Author(s):  
Go Kasuya ◽  
Takanori Nakane ◽  
Takeshi Yokoyama ◽  
Yanyan Jia ◽  
Masato Inoue ◽  
...  

AbstractMaintenance of cell volume against osmotic change is crucial for proper cell functions, such as cell proliferation and migration. The leucine-rich repeat-containing 8 (LRRC8) proteins are anion selective channels, and were recently identified as pore components of the volume-regulated anion channels (VRACs), which extrude anions to decrease the cell volume upon cell-swelling. Here, we present the human LRRC8A structure, determined by a single-particle cryo-electron microscopy analysis. The sea anemone-like structure represents a trimer of dimers assembly, rather than a symmetrical hexameric assembly. The four-spanning transmembrane region has a gap junction channel-like membrane topology, while the LRR region containing 15 leucine-rich repeats forms a long twisted arc. The channel pore is along the central axis and constricted on the extracellular side, where the highly conserved polar and charged residues at the tip of the extracellular helix contribute to the anion and other osmolyte permeability. Comparing the two structural populations facilitated the identification of both compact and relaxed conformations, suggesting that the LRR region is flexible and mobile with rigid-body motions, which might be implicated in structural transitions upon pore opening. Overall, our structure provides a framework for understanding the molecular mechanisms of this unique class of ion channels.


2007 ◽  
Vol 179 (4) ◽  
pp. i12-i12
Author(s):  
Li-Ting Chien ◽  
H. Criss Hartzell
Keyword(s):  

2019 ◽  
Vol 20 (14) ◽  
pp. 3475 ◽  
Author(s):  
Michael Kittl ◽  
Katharina Helm ◽  
Marlena Beyreis ◽  
Christian Mayr ◽  
Martin Gaisberger ◽  
...  

Many cell types express an acid-sensitive outwardly rectifying (ASOR) anion current of an unknown function. We characterized such a current in BV-2 microglial cells and then studied its interrelation with the volume-sensitive outwardly rectifying (VSOR) Cl− current and the effect of acidosis on cell volume regulation. We used patch clamp, the Coulter method, and the pH-sensitive dye BCECF to measure Cl− currents and cell membrane potentials, mean cell volume, and intracellular pH, respectively. The ASOR current activated at pH ≤ 5.0 and displayed an I− > Cl− > gluconate− permeability sequence. When compared to the VSOR current, it was similarly sensitive to DIDS, but less sensitive to DCPIB, and insensitive to tamoxifen. Under acidic conditions, the ASOR current was the dominating Cl− conductance, while the VSOR current was apparently inactivated. Acidification caused cell swelling under isotonic conditions and prevented the regulatory volume decrease under hypotonicity. We conclude that acidification, associated with activation of the ASOR- and inactivation of the VSOR current, massively impairs cell volume homeostasis. ASOR current activation could affect microglial function under acidotoxic conditions, since acidosis is a hallmark of pathophysiological events like inflammation, stroke or ischemia and migration and phagocytosis in microglial cells are closely related to cell volume regulation.


2014 ◽  
Vol 58 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Sabine Gröbner ◽  
Robert Lukowski ◽  
Ingo B. Autenrieth ◽  
Peter Ruth

2009 ◽  
Vol 101 (2) ◽  
pp. 750-757 ◽  
Author(s):  
Christa W. Habela ◽  
Nola Jean Ernest ◽  
Amanda F. Swindall ◽  
Harald Sontheimer

During brain development, progenitor cells migrate over long distances through narrow and tortuous extracellular spaces posing significant demands on the cell's ability to alter cell volume. This phenotype is recapitulated in primary brain tumors. We demonstrate here that volume changes occurring spontaneously in these cells are mediated by the flux of Cl− along with obligated water across the cell membrane. To do so, glioma cells accumulate Cl− to ∼100 mM, a concentration threefold greater than predicted by the Nernst equation. Shunting this gradient through the sustained opening of exogenously expressed GABA-gated Cl− channels caused a 33% decrease in cell volume and impaired the ability of cells to migrate in a spatially constrained environment. Further, dividing cells condense their cytoplasm prior to mitosis, a phenomenon which is associated with the release of intracellular Cl− as indicated by a 40-mM decrease in [Cl−]i. These findings provide a new framework for considering the role of intracellular Cl− in glioma cells. Here, Cl− serves as an important osmotically active regulator of cell volume being the energetic driving force for volume changes required by immature cells in cell migration and proliferation. This mechanism that was studied in CNS malignancies may be shared with other immature cells in the brain as well.


2012 ◽  
Vol 303 (4) ◽  
pp. C416-C426 ◽  
Author(s):  
Venkanna Pasham ◽  
Anand Rotte ◽  
Wenting Yang ◽  
Christine Zelenak ◽  
Madhuri Bhandaru ◽  
...  

The oxidative stress-responsive kinase 1 (OSR1) is activated by WNK (with no K kinases) and in turn stimulates the thiazide-sensitive Na-Cl cotransporter (NCC) and the furosemide-sensitive Na-K-2Cl cotransporter (NKCC), thus contributing to transport and cell volume regulation. Little is known about extrarenal functions of OSR1. The present study analyzed the impact of decreased OSR1 activity on the function of dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity. DCs were cultured from bone marrow of heterozygous WNK-resistant OSR1 knockin mice ( osr KI) and wild-type mice ( osr WT). Cell volume was estimated from forward scatter in FACS analysis, ROS production from 2′,7′-dichlorodihydrofluorescein-diacetate fluorescence, cytosolic pH (pHi) from 2′,7′- bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein fluorescence, and Na+/H+ exchanger activity from Na+-dependent realkalinization following ammonium pulse and migration utilizing transwell chambers. DCs expressed WNK1, WNK3, NCC, NKCC1, and OSR1. Phosphorylated NKCC1 was reduced in osr KI DCs. Cell volume and pHi were similar in osr KI and osr WT DCs, but Na+/H+ exchanger activity and ROS production were higher in osr KI than in osr WT DCs. Before LPS treatment, migration was similar in osr KI and osr WT DCs. LPS (1 μg/ml), however, increased migration of osr WT DCs but not of osr KI DCs. Na+/H+ exchanger 1 inhibitor cariporide (10 μM) decreased cell volume, intracellular reactive oxygen species (ROS) formation, Na+/H+ exchanger activity, and pHi to a greater extent in osr KI than in osr WT DCs. LPS increased cell volume, Na+/H+ exchanger activity, and ROS formation in osr WT DCs but not in osr KI DCs and blunted the difference between osr KI and osr WT DCs. Na+/H+ exchanger activity in osr WT DCs was increased by the NKCC1 inhibitor furosemide (100 nM) to values similar to those in osr KI DCs. Oxidative stress (10 μM tert-butyl-hydroperoxide) increased Na+/H+ exchanger activity in osr WT DCs but not in osr KI DCs and reversed the difference between genotypes. Cariporide virtually abrogated Na+/H+ exchanger activity in both genotypes and blunted LPS-induced cell swelling and ROS formation in osr WT mice. In conclusion, partial OSR1 deficiency influences Na+/H+ exchanger activity, ROS formation, and migration of dendritic cells.


Author(s):  
A. W. Sedar ◽  
G. H. Bresnick

After experimetnal damage to the retina with a variety of procedures Müller cell hypertrophy and migration occurs. According to Kuwabara and others the reactive process in these injuries is evidenced by a marked increase in amount of glycogen in the Müller cells. These cells were considered originally supporting elements with fiber processes extending throughout the retina from inner limiting membrane to external limiting membrane, but are known now to have high lactic acid dehydrogenase activity and the ability to synthesize glycogen. Since the periodic acid-chromic acid-silver methenamine technique was shown to demonstrate glycogen at the electron microscope level, it was selected to react with glycogen in the fine processes of the Müller cell that ramify among the neural elements in various layers of the retina and demarcate these cells cytologically. The Rhesus monkey was chosen as an example of a well vascularized retina and the rabbit as an example of a avascular retina to explore the possibilities of the technique.


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