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The Angiotensin II Type 1 Receptor-Associated Protein Attenuates Angiotensin II-Mediated Inhibition of the Renal Outer Medullary Potassium Channel in Collecting Duct Cells

Polidoro, Juliano Zequini ; Rebouças, Nancy Amaral ; Girardi, Adriana Castello Costa

Frontiers in physiology, 2021-05, Vol.12, p.642409-642409 [Periódico revisado por pares]

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  • Título:
    The Angiotensin II Type 1 Receptor-Associated Protein Attenuates Angiotensin II-Mediated Inhibition of the Renal Outer Medullary Potassium Channel in Collecting Duct Cells
  • Autor: Polidoro, Juliano Zequini ; Rebouças, Nancy Amaral ; Girardi, Adriana Castello Costa
  • Assuntos: angiotensin II type 1 receptor ; angiotensin II type 1 receptor-associated protein ; c-Src ; K+ channels ; K+ homeostasis ; kidney ; Physiology
  • É parte de: Frontiers in physiology, 2021-05, Vol.12, p.642409-642409
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    This article was submitted to Renal and Epithelial Physiology, a section of the journal Frontiers in Physiology
    Reviewed by: Tianxin Yang, The University of Utah, United States; Carsten Alexander Wagner, University of Zurich, Switzerland
    Edited by: Minolfa C. Prieto, Tulane University, United States
  • Descrição: Adjustments in renal K + excretion constitute a central mechanism for K + homeostasis. The renal outer medullary potassium (ROMK) channel accounts for the major K + secretory route in collecting ducts during basal conditions. Activation of the angiotensin II (Ang II) type 1 receptor (AT1R) by Ang II is known to inhibit ROMK activity under the setting of K + dietary restriction, underscoring the role of the AT1R in K + conservation. The present study aimed to investigate whether an AT1R binding partner, the AT1R-associated protein (ATRAP), impacts Ang II-mediated ROMK regulation in collecting duct cells and, if so, to gain insight into the potential underlying mechanisms. To this end, we overexpressed either ATRAP or β-galactosidase (LacZ; used as a control), in M-1 cells, a model line of cortical collecting duct cells. We then assessed ROMK channel activity by employing a novel fluorescence-based microplate assay. Experiments were performed in the presence of 10 −10 M Ang II or vehicle for 40 min. We observed that Ang II-induced a significant inhibition of ROMK in LacZ, but not in ATRAP-overexpressed M-1 cells. Inhibition of ROMK-mediated K + secretion by Ang II was accompanied by lower ROMK cell surface expression. Conversely, Ang II did not affect the ROMK-cell surface abundance in M-1 cells transfected with ATRAP. Additionally, diminished response to Ang II in M-1 cells overexpressing ATRAP was accompanied by decreased c-Src phosphorylation at the tyrosine 416. Unexpectedly, reduced phospho-c-Src levels were also found in M-1 cells, overexpressing ATRAP treated with vehicle, suggesting that ATRAP can also downregulate this kinase independently of Ang II-AT1R activation. Collectively, our data support that ATRAP attenuates inhibition of ROMK by Ang II in collecting duct cells, presumably by reducing c-Src activation and blocking ROMK internalization. The potential role of ATRAP in K + homeostasis and/or disorders awaits further investigation.
  • Editor: Frontiers Media S.A
  • Idioma: Inglês
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