{rfName}
Ro

Indexed in

License and use

Citations

15

Altmetrics

Analysis of institutional authors

Castellanos AAuthor

Share

July 18, 2019
Publications
>
Article
No

Role of zebrafish ClC-K/barttin channels in apical kidney chloride reabsorption

Publicated to:Journal Of Physiology-London. 597 (15): 3969-3983 - 2019-08-01 597(15), DOI: 10.1113/JP278069

Authors: Pérez-Rius C., Castellanos A., Gaitán-Peñas H., Navarro A., Artuch R., Barrallo-Gimeno A., Estévez R.

Affiliations

Hosp St Joan de Deu, Inst Recerca St Joan de Deu, Clin Biochem Dept, Esplugas de Llobregat, Spain - Author
ISCIII, Ctr Invest Red Enfermedades Raras CIBERER, Madrid, Spain - Author
Traslational Medicine. Genes, Disease and Therapy Program. Physiology and pathology of the functional relationship between glia and neurons - Author
Univ Barcelona, IDIBELL Inst Neurosci, Hosp Llobregat,Unitat Fisiol, Genes Dis & Therapy Program,Dept Ciencies Fisiol, Barcelona, Spain - Author

Abstract

© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society Key points: We have characterized the zebrafish clc-k and barttin proteins, demonstrating that they form a protein complex mediating chloride flux in a similar manner to their mammalian counterparts. As in mammals, in zebrafish, clc-k and barttin are basically expressed in the kidney. Contrary to what is found in mammals, in zebrafish both proteins show an apical localization in the kidney. We have generated the first knockout in zebrafish of a CLC protein. Lack of clc-k in zebrafish resulted in embryonic lethality, possibly caused by a reduction in total chloride content. As a consequence, there is an up-regulation of other chloride channels and other regulatory mechanisms such as renin or the uro-guanylin receptor in the kidney. barttin is mislocalized in vivo when clc-k is not present, indicating that there is a mutual dependence of the protein expression and localization between barttin and clc-k proteins. Abstract: ClC-K/barttin channels are very important for salt transport in the kidney. This function can be clearly seen since mutations in CLCNKB or BSND cause Bartter's syndrome types III and IV, respectively. Working with the freshwater teleost zebrafish, we characterized the genes homologous to the mammalian chloride channel ClC-K and its obligate subunit barttin and we obtained and studied clc-k knockout zebrafish. The zebrafish clc-k/barttin proteins are very similar to their mammalian counterparts, and both proteins are necessary to mediate chloride currents. Localization studies indicated that both proteins are exclusively expressed in the apical membranes of zebrafish kidney tubules. Knockout of clc-k resulted in embryonic lethality. These animals showed barttin mislocalization and a reduction in whole-body chloride concentration, as well as up-regulation of the expression of other chloride channels and renin, and an increase in the kidney expression of the uroguanylin receptor. Our results indicate that apical kidney chloride reabsorption through clc-k/barttin channels is crucial for chloride homeostasis in zebrafish as it is in humans. The zebrafish model could be used as a new in vivo system to study ClC-K function.

Keywords

AdultAnimal cellAnimal experimentAnimal tissueAnimalsApical membraneArticleBarttinBarttin proteinBiochemical analysisBsnd protein, zebrafishCell membraneChloride channelChloride channelsChloride transportChloridesClc k proteinClc-kClcnk geneConcentration (parameter)Controlled studyElectrophysiologyEmbryoGeneGene insertionGene knockoutGenetic analysisHek293 cellsHek293t cell lineHumanHuman cellHumansIn vivo studyKidneyKidney tubule absorptionLethalityMolecular cloningMutationNonhumanOsmotic pressurePriority journalProtein depletionProtein expressionProtein functionProtein localizationProtein transportRatRenal reabsorptionReninUnclassified drugUpregulationUroguanylinWestern blottingZebra fishZebrafishZebrafish proteins

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Physiology-London due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 11/81, thus managing to position itself as a Q1 (Primer Cuartil), in the category Physiology.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.6, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-02, the following number of citations:

  • WoS: 1
  • Scopus: 4
  • Europe PMC: 3

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 13.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 14 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 4.05.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 6 (Altmetric).