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Calcium transients in astrocyte endfeet cause cerebrovascular constrictions

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  • Sean J. Mulligan

    (University of British Columbia)

  • Brian A. MacVicar

    (University of British Columbia)

Abstract

Cerebral blood flow (CBF) is coupled to neuronal activity and is imaged in vivo to map brain activation1. CBF is also modified by afferent projection fibres that release vasoactive neurotransmitters2,3 in the perivascular region, principally on the astrocyte endfeet4,5 that outline cerebral blood vessels6. However, the role of astrocytes in the regulation of cerebrovascular tone remains uncertain. Here we determine the impact of intracellular Ca2+ concentrations ([Ca2+]i) in astrocytes on the diameter of small arterioles by using two-photon Ca2+ uncaging7,8 to increase [Ca2+]i. Vascular constrictions occurred when Ca2+ waves evoked by uncaging propagated into the astrocyte endfeet and caused large increases in [Ca2+]i. The vasoactive neurotransmitter noradrenaline2,3 increased [Ca2+]i in the astrocyte endfeet, the peak of which preceded the onset of arteriole constriction. Depressing increases in astrocyte [Ca2+]i with BAPTA inhibited the vascular constrictions in noradrenaline. We find that constrictions induced in the cerebrovasculature by increased [Ca2+]i in astrocyte endfeet are generated through the phospholipase A2–arachidonic acid pathway and 20-hydroxyeicosatetraenoic acid production. Vasoconstriction by astrocytes is a previously unknown mechanism for the regulation of CBF.

Suggested Citation

  • Sean J. Mulligan & Brian A. MacVicar, 2004. "Calcium transients in astrocyte endfeet cause cerebrovascular constrictions," Nature, Nature, vol. 431(7005), pages 195-199, September.
    • Handle: RePEc:nat:nature:v:431:y:2004:i:7005:d:10.1038_nature02827
    DOI: 10.1038/nature02827
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    Cited by:

    1. Xin Rui Lim & Mohammad M. Abd-Alhaseeb & Michael Ippolito & Masayo Koide & Amanda J. Senatore & Curtis Plante & Ashwini Hariharan & Nick Weir & Thomas A. Longden & Kathryn A. Laprade & James M. Staffo, 2024. "Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. William A. Mills & AnnaLin M. Woo & Shan Jiang & Joelle Martin & Dayana Surendran & Matthew Bergstresser & Ian F. Kimbrough & Ukpong B. Eyo & Michael V. Sofroniew & Harald Sontheimer, 2022. "Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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