Faculty Collaboration Database

Astrocyte-mediated activation of neuronal kainate receptors. Proc Natl Acad Sci U S A 2004 Mar 02;101(9):3172-7

Date

02/10/2004

Pubmed ID

14766987

Pubmed Central ID

PMC365762

DOI

10.1073/pnas.0306731101

Scopus ID

2-s2.0-1542357665 (requires institutional sign-in at Scopus site)   189 Citations

Abstract

Exogenous kainate receptor agonists have been shown to modulate inhibitory synaptic transmission in the hippocampus, but the pathways involved in physiological activation of the receptors remain largely unknown. Accumulating evidence indicates that astrocytes can release glutamate in a Ca(2+)-dependent manner and signal to neighboring neurons. We tested the hypothesis that astrocyte-derived glutamate activates kainate receptors on hippocampal interneurons. We report here that elevation of intracellular Ca(2+) in astrocytes, induced by uncaging Ca(2+), o-nitrophenyl-EGTA, increased action potential-driven spontaneous inhibitory postsynaptic currents in nearby interneurons in rat hippocampal slices. This effect was blocked by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptor antagonists, but not by selective AMPA receptor or N-methyl-d-aspartate receptor antagonists. This pharmacological profile indicates that kainate receptors were activated during Ca(2+) elevation in astrocytes. Kainate receptors containing the GluR5 subunit seemed to mediate the observed effect because a selective GluR5-containing kainate receptor antagonist blocked the changes in sIPSCs induced by Ca(2+) uncaging, and bath application of a selective GluR5-containing receptor agonist robustly potentiated sIPSCs. When tetrodotoxin was included to block action potentials, Ca(2+) uncaging induced a small decrease in the frequency of miniature inhibitory postsynaptic currents, which was not affected by AMPA/kainate receptor antagonists. Our data suggest that an astrocyte-derived, nonsynaptic source of glutamate represents a signaling pathway that can activate neuronal kainate receptors. By modulating the activity of interneurons, astrocytes may play a critical role in circuit function of hippocampus.

Author List

Liu QS, Xu Q, Arcuino G, Kang J, 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

Animals
Astrocytes
Calcium Signaling
Chelating Agents
Egtazic Acid
Hippocampus
In Vitro Techniques
Interneurons
Isoquinolines
Neurons
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Receptors, Kainic Acid
Receptors, N-Methyl-D-Aspartate
Tetrazoles