The expanding toolbox to study the LRRC8-formed volume-regulated anion channel VRAC

Kolobkova, Yulia; Pervaiz, Sumaira; Stauber, Tobias

doi:10.1016/bs.ctm.2021.10.001

Cited by 7 publications

(4 citation statements)

References 201 publications

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“…Furthermore, it has been reported that, by activating the intermediateconductance Ca 2+ -activated K + channel (IK Ca ), extracellular 5'-guanosine-triphosphate (GTP) hyperpolarizes C2C12 cells from a mean value of −15 mV to approximately −75 mV and increases myosin heavy chain (MHC) expression [35][36][37]. VRAC is a plasma membrane channel formed by heteromers of leucine-rich repeat containing family 8 (LRRC8) members that mediates the flux of Cl − and organic osmolytes in a variety of physiological processes [38][39][40][41][42]. Using an optical activity sensor [43], VRAC was shown to be transiently activated during the early stage of C2C12 (a mouse skeletal muscle myoblast cell line that expresses all five LRRC8 family members [44]) differentiation, which was also accompanied by a reduction in intracellular chloride [34].…”

Section: Membrane Hyperpolarizationmentioning

confidence: 99%

Ion Channels and Transporters in Muscle Cell Differentiation

Chen

Nia

Stauber

2021

IJMS

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Investigations on ion channels in muscle tissues have mainly focused on physiological muscle function and related disorders, but emerging evidence supports a critical role of ion channels and transporters in developmental processes, such as controlling the myogenic commitment of stem cells. In this review, we provide an overview of ion channels and transporters that influence skeletal muscle myoblast differentiation, cardiac differentiation from pluripotent stem cells, as well as vascular smooth muscle cell differentiation. We highlight examples of model organisms or patients with mutations in ion channels. Furthermore, a potential underlying molecular mechanism involving hyperpolarization of the resting membrane potential and a series of calcium signaling is discussed.

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Section: Membrane Hyperpolarizationmentioning

confidence: 99%

Ion Channels and Transporters in Muscle Cell Differentiation

Chen

Nia

Stauber

2021

IJMS

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“…It is worth noting that a significant amount of research on VRAC activation was carried out before the identification of its molecular components ( Stauber, 2015 ; Pedersen et al, 2016 ; Strange et al, 2019 ; Bertelli et al, 2021 ). The identification of LRRC8 heteromers as essential constituents allows using an increasing repertoire of molecular biological tools ( Qiu et al, 2014 ; Voss et al, 2014 ; Kolobkova et al, 2021 ). In particular, the determination of LRRC8 complexes structures ( Deneka et al, 2018 ; Kasuya et al, 2018 ; Kefauver et al, 2018 ; Kern et al, 2019 ; Nakamura et al, 2020 ; Deneka et al, 2021 ; Kern et al, 2023 ; Rutz et al, 2023 ; Takahashi et al, 2023 ) and other studies on the subunit composition and structure-function relationships ( Gaitán-Peñas et al, 2016 ; Ullrich et al, 2016 ; Lutter et al, 2017 ; Schober et al, 2017 ; Yamada and Strange, 2018 ; Zhou et al, 2018 ; Pervaiz et al, 2019 ; Yamada et al, 2021 ; Bertelli et al, 2022 ), will greatly contribute to the understanding of the VRAC activation mechanism(s).…”

Section: Discussionmentioning

confidence: 99%

Trends in volume-regulated anion channel (VRAC) research: visualization and bibliometric analysis from 2014 to 2022

et al. 2023

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Objective: In this study, we utilized bibliometric methods to assess the worldwide scientific output and identify hotspots related to the research on the volume-regulated anion channel (VRAC) from 2014 to 2022.Methods: From Web of Science, we obtained studies related to VRAC published from 2014 to 2022. To analyzed the data, we utilized VOSviewer, a tool for visualizing network, to create networks based on the collaboration between countries, institutions, and authors. Additionally, we performed an analysis of journal co-citation, document citation, and co-occurrence of keywords. Furthermore, we employed CiteSpace (6.1. R6 Advanced) to analyzed keywords and co-cited references with the strongest burst.Results: The final analysis included a total of 278 related articles and reviews, covering the period from 2014 to 2022. The United States emerged as the leading country contributing to this field, while the University of Copenhagen stood out as the most prominent institution. The author with most publications and most citations was Thomas J. Jentsch. Among the cited references, the article by Voss et al. published in Science (2014) gained significant attention for its identification of LRRC8 heteromers as a crucial component of the volume-regulated anion channel VRAC. Pflügers Archiv European Journal of Physiology and Journal of Physiology-London were the leading journals in terms of the quantity of associated articles and citations. Through the analysis of keyword co-occurrence, it was discovered that VRAC is involved in various physiological processes including cell growth, migration, apoptosis, swelling, and myogenesis, as well as anion and organic osmolyte transport including chloride, taurine, glutamate and ATP. VRAC is also associated with related ion channels such as TMEM16A, TMEM16F, pannexin, and CFTR, and associated with various diseases including epilepsy, leukodystrophy, atherosclerosis, hypertension, cerebral edema, stroke, and different types of cancer including gastric cancer, glioblastoma and hepatocellular carcinoma. Furthermore, VRAC is involved in anti-tumor drug resistance by regulating the uptake of platinum-based drugs and temozolomide. Additionally, VRAC has been studied in the context of pharmacology involving DCPIB and flavonoids.Conclusion: The aim of this bibliometric analysis is to provide an overall perspective for research on VRAC. VRAC has become a topic of increasing interest, and our analysis shows that it continues to be a prominent area. This study offers insights into the investigation of VRAC channel and may guide researchers in identifying new directions for future research.

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“…VRACs are reported to require intracellular ATP and basal levels of intracellular calcium and can be inhibited by various drugs, none of which is, however, specific [34]. In addition to their participation in RVD mechanisms, VRACs have also been proposed to play a role in apoptosis, cell proliferation and migration, cancer drug resistance, membrane potential modulation, cell-cell communication, secretion and epithelial transport [28,[35][36][37][38]. The identification of the genes that encode the protein(s) underlying VRACs has been challenging.…”

Section: Structure-function Relationships Of Vracsmentioning

confidence: 99%

VRAC Channels and the Cellular Redox Balance

Morabito¹,

Spinelli²,

Marino³

et al. 2024

Physiology

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Volume-regulated anion channels (VRAC) are mainly involved in the regulated transport of osmolytes such as ions or small organic compounds across the plasma membrane during anisosmotic cell swelling. However, they also play additional roles in various pathophysiological processes, such as the transport of metabolites and drugs, extracellular signal transduction and anti-cancer drug resistance. These channels are formed by heteromers of LRRC8 proteins, of which LRRC8A is the essential subunit that combines with its paralogs LRRC8B–E to form hexameric complexes. Despite the extensive research devoted to the understanding of VRACs functions, different aspects of these channels are still to be characterized in depth. In this chapter, recent findings concerning the involvement of VRAC channels in the cellular redox balance will be summarized. Also, their relevance as potential targets of antioxidant therapies will be discussed.

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The expanding toolbox to study the LRRC8-formed volume-regulated anion channel VRAC

Cited by 7 publications

References 201 publications

Ion Channels and Transporters in Muscle Cell Differentiation

Ion Channels and Transporters in Muscle Cell Differentiation

Trends in volume-regulated anion channel (VRAC) research: visualization and bibliometric analysis from 2014 to 2022

VRAC Channels and the Cellular Redox Balance

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