Faculty Collaboration Database

Signaling at the gliovascular interface. J Neurosci 2003 Oct 08;23(27):9254-62

Date

10/10/2003

Pubmed ID

14534260

Pubmed Central ID

PMC6740832

DOI

10.1523/JNEUROSCI.23-27-09254.2003

Scopus ID

2-s2.0-0141988699 (requires institutional sign-in at Scopus site)   499 Citations

Abstract

Advances in fluorescent calcium indicating dyes over the past decade have identified calcium signaling as the tool by which astrocytes communicate among themselves and with neighboring neurons. Studies of astrocyte-neuron interactions have shown that calcium signaling is a potent modulator of the strength of both excitatory and inhibitory synapses. The concept that astrocytes possess a mechanism for rapid cell communication has not been incorporated, however, into the supportive functions of astrocytes. Because many of the classical tasks of astrocytes are linked to the blood-brain barrier, we have here examined the expression of proteins required for calcium signaling in their vascular end-foot processes. The gap junction protein, Cx43, was expressed intensively around the vessels interconnecting astrocytic end-foot processes. These gap junctions permitted diffusion of Lucifer yellow, specifically along the path of glial end feet apposed to the vessel wall. The purinergic receptors, P2Y(2) and P2Y(4), were also strongly expressed at the gliovascular interface and colocalized with GFAP around larger vessels in cortex. Multiphoton imaging of freshly prepared brain slices loaded with Fluo-4/AM revealed that ATP mobilized cytosolic calcium in astrocytic end feet, whereas electrical stimulation triggered calcium waves propagating along the vessel wall. Brain endothelial cells and pericytes were physically separated from astrocytes by the basal lamina and responded only weakly to ATP. These observations identify astrocytic end-foot processes plastered at the vessel wall as a center for purinergic signaling. It is speculated that calcium signaling may play a role in astrocytic functions related to the blood-brain barrier, including blood flow regulation, metabolic trafficking, and water homeostasis.

Author List

Simard M, Arcuino G, Takano T, Liu QS, Nedergaard M

Author

Qing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Astrocytes
Basement Membrane
Blood-Brain Barrier
Brain
Calcium Signaling
Cerebrovascular Circulation
Connexin 43
Diffusion
Endothelium, Vascular
Fluorescent Dyes
Gap Junctions
Glial Fibrillary Acidic Protein
In Vitro Techniques
Male
Microcirculation
Patch-Clamp Techniques
Pericytes
Rats
Rats, Sprague-Dawley
Receptors, Purinergic P2
Receptors, Purinergic P2Y2