Angiotensin II, ATP and high extracellular potassium induced intracellular calcium responses in primary rat brain endothelial cell cultures

Carlos Antonio García-Carlos, Julio Andrés Camargo-Loaiza, Denisse García-Villa, José Guillermo López-Cervantes, J. Abraham Domínguez-Avila, Gustavo A. González-Aguilar, Humberto Astiazaran-Garcia, Marcelino Montiel-Herrera*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The meninges shield the nervous system from diverse, rather harmful stimuli and pathogens from the periphery. This tissue is composed of brain endothelial cells (BECs) that express diverse ion channels and chemical-transmitter receptors also expressed by neurons and glial cells to communicate with each other. However, information about the effects of ATP and angiotensin II on BECs is scarce, despite their essential roles in blood physiology. This work investigated in vitro if BECs from the meninges from rat forebrain respond to ATP, angiotensin II and high extracellular potassium, with intracellular calcium mobilizations and its second messenger-associated pathways. We found that in primary BEC cultures, both ATP and angiotensin II produced intracellular calcium responses linked to the activation of inositol trisphosphate receptors and ryanodine receptors, which led to calcium release from intracellular stores. We also used RT-PCR to explore what potassium channel subunits are expressed by primary BEC cultures and freshly isolated meningeal tissue, and which might be linked to the observed effects. We found that BECs mainly expressed the inward rectifier potassium channel subunits Kir1.1, Kir3.3, Kir 4.1 and Kir6.2. This study contributes to the understanding of the functions elicited by ATP and angiotensin II in BECs from rat meninges. SIGNIFICANCE OF THE STUDY: Brain endothelial cells (BECs) express diverse ion channels and membrane receptors, which they might use to communicate with neurons and glia. This work investigated in vitro, if BECs from the rat forebrain respond to angiotensin II and ATP with intracellular calcium mobilizations. We found that these cells did respond to said substances with intracellular calcium mobilizations linked to inositol trisphosphate and ryanodine receptor activation, which led to calcium release from intracellular stores. These findings are important because they might uncover routes of active communication between brain cells and endothelial cells.

Original languageEnglish
Pages (from-to)688-698
Number of pages11
JournalCell Biochemistry and Function
Issue number5
StatePublished - Jul 2021
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to Bertha I. Pacheco Moreno and Karla E. Zavalza Ortega for their technical support.

Publisher Copyright:
© 2021 John Wiley & Sons Ltd


  • angiotensins
  • ATP
  • cell physiology
  • intracellular calcium
  • meninges
  • potassium channels


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