Calcium transients in astrocyte endfeet cause cerebrovascular constrictions.
Cerebral blood flow (CBF) is coupled to neuronal activity and is imaged in vivo to map brain activation. CBF is also modified by afferent projection fibres that release vasoactive neurotransmitters in the perivascular region, principally on the astrocyte endfeet that outline cerebral blood vessels. However, the role of astrocytes in the regulation of cerebrovascular tone remains uncertain. Here we determine the impact of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in astrocytes on the diameter of small arterioles by using two-photon Ca(2+) uncaging to increase [Ca(2+)](i). Vascular constrictions occurred when Ca(2+) waves evoked by uncaging propagated into the astrocyte endfeet and caused large increases in [Ca(2+)](i). The vasoactive neurotransmitter noradrenaline increased [Ca(2+)](i) in the astrocyte endfeet, the peak of which preceded the onset of arteriole constriction. Depressing increases in astrocyte [Ca(2+)](i) with BAPTA inhibited the vascular constrictions in noradrenaline. We find that constrictions induced in the cerebrovasculature by increased [Ca(2+)](i) in astrocyte endfeet are generated through the phospholipase A(2)-arachidonic acid pathway and 20-hydroxyeicosatetraenoic acid production. Vasoconstriction by astrocytes is a previously unknown mechanism for the regulation of CBF.
Mulligan
Sean J
SJ
Brain Research Centre, Department of Psychiatry, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, Canada, V6T 2B5.
MacVicar
Brian A
BA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010741:Phospholipases A / Q000378:metabolism; D010782:Photolysis; D017785:Photons; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D004533:Egtazic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D010741:Phospholipases A; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D009638:Norepinephrine