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

Abstract

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.

Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC. Part 1: from its discovery and phenotype characterization to the molecular entity identification

“…Since the discovery of VSOR/VRAC, its biophysical and physiological properties have been extensively investigated and well summarized in review articles in the early period [ 3 , 4 , 29 ] and in the last few years [ 30 – 35 ] with including information accumulated on the basis of the recent identification of LRRC8 as the core molecule of VSOR/VRAC [ 8 , 9 ]. The pharmacological properties of VSOR/VRAC have also been extensively studied, as summarized in review articles [ 3 , 4 , 32 , 34 , 36 , 37 ]. Here, these properties are updated by taking the latest studies into consideration.…”

“…None of the VSOR/VRAC blockers are unfortunately selective, as summarized in recent review articles [ 32 , 34 , 36 , 37 ]. Most of the VSOR/VRAC blockers can be classified into three groups (Table 3 ): (1) Conventional type of Cl − channel blockers with two aromatic rings connected with a chain of one to four atoms (see Fig.…”

“…In contrast, DCPIB was shown to be ineffective in blocking CaCC, CFTR, and ClC-1/3/4/5/K1 Cl − channel activities [ 100 ] as well as Maxi-Cl [ 101 , 102 ] and ASOR/PAC [ 72 ] anion channel activities. However, it must be noted that even DCPIB exhibits off-target effects on a variety of other ion channels and transporters, as summarized in review articles [ 34 , 37 , 99 , 103 ]. In addition, one also needs to bear the possibility in mind that DCPIB may suppress, to a certain extent, some molecularly unidentified Ca 2+ -activated Cl − currents [ 104 ] and acid-activated Cl − currents [ 105 ].…”