title: Calcium dynamics in cortical astrocytes and arterioles during neurovascular coupling.
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.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Vermont, Burlington 05405-0068, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Filosa
authors.forename: Adrian D
authors.initials: AD
authors.lastname: Bonev
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001896:Boron Compounds / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling; D002540:Cerebral Cortex / Q000098:blood supply* / Q000166:cytology*; D002560:Cerebrovascular Circulation; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D006940:Hyperemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018715:Microscopy, Video; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000648:ultrastructure; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: C095756:1-aminoindan-1,5-dicarboxylic acid; D001896:Boron Compounds; D015220:Calcium Channels; D007189:Indans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011725:Pyridines; D018160:Receptors, Cytoplasmic and Nuclear; D018094:Receptors, Metabotropic Glutamate; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D013779:Tetrodotoxin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C121465:6-methyl-2-(phenylethynyl)pyridine; D015544:Inositol 1,4,5-Trisphosphate; C109986:2-aminoethoxydiphenyl borate; D009543:Nifedipine