Acid- and Volume-Sensitive Chloride Currents in Human Chondrocytes

Kittl, Michael; Winklmayr, Martina; Helm, Katharina; Lettner, Johannes; Gaisberger, Martin; Ritter, Markus; Jakab, Martin

doi:10.3389/fcell.2020.583131

Cited by 22 publications

(22 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, sensitivity of ASOR currents to 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) was observed at 100 µM in HEK293 cells (Capurro et al, 2015) and in kidney epithelial cells (Valinsky et al, 2017) but never in HeLa cells (Sato-Numata et al, 2016). A relatively VSOR-selective blocker, 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5yl)oxybutyric acid (DCPIB), was shown to be totally ineffective at blocking ASOR currents in HeLa cells (Sato-Numata et al, 2016) and microglial BV-2 cells (Kittl et al, 2019) at 10 µM but was found to be able to suppress not only VSOR but also ASOR currents in immortalized human chondrocyte-derived C28/I2 cells at 10 µM (Kittl et al, 2020).…”

Section: Cell Typesmentioning

confidence: 99%

“…Also, ASOR exhibits much higher sensitivity to suramin, DIOA, arachidonic acid and niflumic acid compared to VSOR (Sato- . Moreover, it must be noted that ASOR and VSOR currents can be simultaneously activated and then develop in an additive fashion in an acidic and hypoosmotic solution (Lambert and Oberwinkler, 2005;Yamamoto and Ehara, 2006;Matsuda et al, 2010b;Kittl et al, 2020), strongly suggesting independent activation of ASOR and VSOR channel molecules. Recently, the leucine-rich repeats containing 8A (LRRC8A) was identified as the core component of VSOR (Qiu et al, 2014;Voss et al, 2014), and functional VSOR activity was shown to require, in addition to LRRC8A, at least one of LRRC8A paralogs (LRRC8B/C/D/E) (Voss et al, 2014;Syeda et al, 2016).…”

Section: Molecular Identity Of the Asor/pac Core Componentmentioning

confidence: 99%

See 1 more Smart Citation

Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 2: Functional and Molecular Properties of ASOR/PAC Channels and Their Roles in Cell Volume Dysregulation and Acidotoxic Cell Death

Okada

Sato-Numata

Sabirov

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

For survival and functions of animal cells, cell volume regulation (CVR) is essential. Major hallmarks of necrotic and apoptotic cell death are persistent cell swelling and shrinkage, and thus they are termed the necrotic volume increase (NVI) and the apoptotic volume decrease (AVD), respectively. A number of ubiquitously expressed anion and cation channels play essential roles not only in CVR but also in cell death induction. This series of review articles address the question how cell death is induced or protected with using ubiquitously expressed ion channels such as swelling-activated anion channels, acid-activated anion channels, and several types of TRP cation channels including TRPM2 and TRPM7. In the Part 1, we described the roles of swelling-activated VSOR/VRAC anion channels. Here, the Part 2 focuses on the roles of the acid-sensitive outwardly rectifying (ASOR) anion channel, also called the proton-activated chloride (PAC) anion channel, which is activated by extracellular protons in a manner sharply dependent on ambient temperature. First, we summarize phenotypical properties, the molecular identity, and the three-dimensional structure of ASOR/PAC. Second, we highlight the unique roles of ASOR/PAC in CVR dysfunction and in the induction of or protection from acidotoxic cell death under acidosis and ischemic conditions.

show abstract

Section: Cell Typesmentioning

confidence: 99%

Section: Molecular Identity Of the Asor/pac Core Componentmentioning

confidence: 99%

Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 2: Functional and Molecular Properties of ASOR/PAC Channels and Their Roles in Cell Volume Dysregulation and Acidotoxic Cell Death

Okada

Sato-Numata

Sabirov

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…As described above, vesicular LRRC8 channels/LysoVRACs may play a role for the flux of anions across the vesicular membrane, and their importance in VVR has been recognized ( Li et al, 2020 ; Osei-Owusu et al, 2021 ). A role for TMEM206/ASOR/PAORAC seems feasible, and an eventual functional coupling of vesicular VSOR and ASOR channels/currents, as described to occur in the PM ( Nobles et al, 2004 ; Lambert and Oberwinkler, 2005 ; Kittl et al, 2019 , 2020 ), awaits future investigation.…”

Section: Vesicular Volume Regulationmentioning

confidence: 98%

“…TMEM206 has been shown to interact with Akt ( Zhao et al, 2019 ) and to contribute to acid-induced CD ( Osei-Owusu et al, 2020 ). The ASOR current is characterized by activation at pH values < 5.0, strong outward rectification, activation at positive transmembrane potentials, and sensitivity to typical Cl – channel blockers ( Sato-Numata et al, 2013 , 2017 ; Kittl et al, 2019 , 2020 ; Ullrich et al, 2019 ). In contrast to CLCs, which are inhibited by extracellular/luminal acidic pH ( Scheel et al, 2005 ; Jentsch, 2007 ; Jentsch and Pusch, 2018 ), ASOR is activated by it.…”

Section: Water Ions and Their Channels And Transporters In Pinocytosismentioning

confidence: 99%

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

Ritter

Bresgen

Kerschbaum

2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

The volumes of a cell [cell volume (CV)] and its organelles are adjusted by osmoregulatory processes. During pinocytosis, extracellular fluid volume equivalent to its CV is incorporated within an hour and membrane area equivalent to the cell’s surface within 30 min. Since neither fluid uptake nor membrane consumption leads to swelling or shrinkage, cells must be equipped with potent volume regulatory mechanisms. Normally, cells respond to outwardly or inwardly directed osmotic gradients by a volume decrease and increase, respectively, i.e., they shrink or swell but then try to recover their CV. However, when a cell death (CD) pathway is triggered, CV persistently decreases in isotonic conditions in apoptosis and it increases in necrosis. One type of CD associated with cell swelling is due to a dysfunctional pinocytosis. Methuosis, a non-apoptotic CD phenotype, occurs when cells accumulate too much fluid by macropinocytosis. In contrast to functional pinocytosis, in methuosis, macropinosomes neither recycle nor fuse with lysosomes but with each other to form giant vacuoles, which finally cause rupture of the plasma membrane (PM). Understanding methuosis longs for the understanding of the ionic mechanisms of cell volume regulation (CVR) and vesicular volume regulation (VVR). In nascent macropinosomes, ion channels and transporters are derived from the PM. Along trafficking from the PM to the perinuclear area, the equipment of channels and transporters of the vesicle membrane changes by retrieval, addition, and recycling from and back to the PM, causing profound changes in vesicular ion concentrations, acidification, and—most importantly—shrinkage of the macropinosome, which is indispensable for its proper targeting and cargo processing. In this review, we discuss ion and water transport mechanisms with respect to CVR and VVR and with special emphasis on pinocytosis and methuosis. We describe various aspects of the complex mutual interplay between extracellular and intracellular ions and ion gradients, the PM and vesicular membrane, phosphoinositides, monomeric G proteins and their targets, as well as the submembranous cytoskeleton. Our aim is to highlight important cellular mechanisms, components, and processes that may lead to methuotic CD upon their derangement.

show abstract

“…Chloride channels regulate chondrogenesis in chicken mandibular mesenchymal cells [ 145 ]. Hypotonic solution and extracellular acidification elicited a volume-sensitive outwardly rectifying Cl – current followed by a regulatory volume decrease and an acid-sensitive outwardly rectifying Cl – current, respectively [ 146 ]. Hypotonic solution-induced Cl – current and regulatory volume decrease responses occurred in isolated rabbit and articular chondrocytes [ 89 , 147 , 148 ].…”

Section: Mechanical Responses Of Nmda Receptors Asics Chloride Chanmentioning

confidence: 99%

Mechanosensory and mechanotransductive processes mediated by ion channels in articular chondrocytes: Potential therapeutic targets for osteoarthritis

et al. 2021

View full text Add to dashboard Cite

Articular cartilage consists of an extracellular matrix including many proteins as well as embedded chondrocytes. Articular cartilage formation and function are influenced by mechanical forces. Hind limb unloading or simulated microgravity causes articular cartilage loss, suggesting the importance of the healthy mechanical environment in articular cartilage homeostasis and implying a significant role of appropriate mechanical stimulation in articular cartilage degeneration. Mechanosensitive ion channels participate in regulating the metabolism of articular chondrocytes, including matrix protein production and extracellular matrix synthesis. Mechanical stimuli, including fluid shear stress, stretch, compression and cell swelling and decreased mechanical conditions (such as simulated microgravity) can alter the membrane potential and regulate the metabolism of articular chondrocytes via transmembrane ion channel-induced ionic fluxes. This process includes Ca 2+ influx and the resulting mobilization of Ca 2+ that is due to massive released Ca 2+ from stores, intracellular cation efflux and extracellular cation influx. This review brings together published information on mechanosensitive ion channels, such as stretch-activated channels (SACs), voltage-gated Ca 2+ channels (VGCCs), large conductance Ca 2+ -activated K + channels (BK Ca channels), Ca 2+ -activated K + channels (SK Ca channels), voltage-activated H + channels (VAHCs), acid sensing ion channels (ASICs), transient receptor potential (TRP) family channels, and piezo1/2 channels. Data based on epithelial sodium channels (ENaCs), purinergic receptors and N-methyl-d-aspartate (NMDA) receptors are also included. These channels mediate mechanoelectrical physiological processes essential for converting physical force signals into biological signals. The primary channel-mediated effects and signaling pathways regulated by these mechanosensitive ion channels can influence the progression of osteoarthritis during the mechanosensory and mechanoadaptive process of articular chondrocytes.

show abstract

Acid- and Volume-Sensitive Chloride Currents in Human Chondrocytes

Cited by 22 publications

References 78 publications

Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 2: Functional and Molecular Properties of ASOR/PAC Channels and Their Roles in Cell Volume Dysregulation and Acidotoxic Cell Death

Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 2: Functional and Molecular Properties of ASOR/PAC Channels and Their Roles in Cell Volume Dysregulation and Acidotoxic Cell Death

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

Mechanosensory and mechanotransductive processes mediated by ion channels in articular chondrocytes: Potential therapeutic targets for osteoarthritis

Contact Info

Product

Resources

About