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Circulation Research. 2004;95:e73-e81
Published online before print October 21, 2004, doi: 10.1161/01.RES.0000148636.60732.2e
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(Circulation Research. 2004;95:e73.)
© 2004 American Heart Association, Inc.


UltraRapid Communication

Calcium Dynamics in Cortical Astrocytes and Arterioles During Neurovascular Coupling

Jessica A. Filosa, Adrian D. Bonev, Mark T. Nelson

From the Department of Pharmacology, College of Medicine, University of Vermont, Burlington.

Correspondence to Mark T. Nelson, PhD, Professor and Chair, Department of Pharmacology, University of Vermont, Given Building, Room B-333, 89 Beaumont Ave, Burlington VT 05405-0068. E-mail Mark.Nelson{at}uvm.edu

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.


Key Words: astrocytes • calcium • functional hyperemia • neurovascular • myocytes




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