Abstract
Neuronal activity in the brain is thought to be coupled to cerebral arterioles (functional hyperemia) through Ca2+ signals in astrocytes. Although functional hyperemia occurs rapidly, within seconds, such rapid signaling has not been demonstrated in situ, and Ca2+ measurements in parenchymal arterioles are still lacking. Using a laser scanning confocal microscope and fluorescence Ca2+ indicators, we provide the first evidence that in a brain slice preparation, increased neuronal activity by electrical stimulation (ES) is rapidly signaled, within seconds, to cerebral arterioles and is associated with astrocytic Ca2+ waves. Smooth muscle cells in parenchymal arterioles exhibited Ca2+ and diameter oscillations ("vasomotion") that were rapidly suppressed by ES. The neuronal-mediated Ca2+ rise in cortical astrocytes was dependent on intracellular (inositol trisphosphate [IP3]) and extracellular voltage-dependent Ca2+ channel sources. The Na+ channel blocker tetrodotoxin prevented the rise in astrocytic [Ca2+]i and the suppression of Ca2+ oscillations in parenchymal arterioles to ES, indicating that neuronal activity was necessary for both events. Activation of metabotropic glutamate receptors in astrocytes significantly decreased the frequency of Ca2+ oscillations in parenchymal arterioles. This study supports the concept that astrocytic Ca2+ changes signal the cerebral microvasculature and indicate the novel concept that this communication occurs through the suppression of arteriolar [Ca2+]i oscillations and corresponding vasomotion. The full text of this article is available online at http://circres.ahajournals.org.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
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Animals
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Arterioles / drug effects
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Arterioles / metabolism
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Astrocytes / drug effects
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Astrocytes / metabolism*
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Boron Compounds / pharmacology
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Calcium Channels / physiology
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Calcium Signaling*
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Cerebral Cortex / blood supply*
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Cerebral Cortex / cytology*
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Cerebrovascular Circulation*
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Cycloleucine / analogs & derivatives*
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Cycloleucine / pharmacology
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Electric Stimulation
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Hyperemia / physiopathology*
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In Vitro Techniques
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Indans / pharmacology
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Inositol 1,4,5-Trisphosphate / physiology
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Inositol 1,4,5-Trisphosphate Receptors
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Microscopy, Video
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Muscle, Smooth, Vascular / metabolism
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Muscle, Smooth, Vascular / ultrastructure
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Myocytes, Smooth Muscle / metabolism
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Neurons / physiology*
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Nifedipine / pharmacology
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Pyridines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / agonists
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Sodium Channel Blockers / pharmacology
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Sodium Channels / drug effects
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Synaptic Transmission / drug effects
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Tetrodotoxin / pharmacology
Substances
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1-aminoindan-1,5-dicarboxylic acid
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Boron Compounds
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Calcium Channels
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Indans
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Inositol 1,4,5-Trisphosphate Receptors
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Pyridines
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Receptors, Cytoplasmic and Nuclear
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Receptors, Metabotropic Glutamate
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Sodium Channel Blockers
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Sodium Channels
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Cycloleucine
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1-amino-1,3-dicarboxycyclopentane
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Tetrodotoxin
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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6-methyl-2-(phenylethynyl)pyridine
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Inositol 1,4,5-Trisphosphate
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2-aminoethoxydiphenyl borate
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Nifedipine