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Mechanisms of ATP‐ and glutamate‐mediated calcium signaling in white matter astrocytes
Author(s) -
Hamilton Nicola,
Vayro Steven,
Kirchhoff Frank,
Verkhratsky Alexej,
Robbins Jon,
Gorecki Dariuz C.,
Butt Arthur M.
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20649
Subject(s) - glutamate receptor , biology , metabotropic glutamate receptor , astrocyte , microbiology and biotechnology , ionotropic effect , nmda receptor , metabotropic receptor , neuroscience , neuroglia , ampa receptor , receptor , biochemistry , central nervous system
Neurotransmitters released at synapses mediate Ca 2+ signaling in astrocytes in CNS grey matter. Here, we show that ATP and glutamate evoke these Ca 2+ signals in white matter astrocytes of the mouse optic nerve, a tract that contains neither neuronal cell bodies nor synapses. We further demonstrate that action potentials along white matter axons trigger the release of ATP and the intercellular propagation of astroglial Ca 2+ signals. These mechanisms were studied in astrocytes in intact optic nerves isolated from transgenic mice expressing enhanced green fluorescent protein (EGFP) under control of the human glial fibrillary acidic protein promoter (GFAP) by Fura‐2 ratiometric Ca 2+ imaging. ATP evoked astroglial Ca 2+ signals predominantly via metabotropic P2Y 1 and ionotropic P2X 7 purinoceptors. Glutamate acted on both AMPA‐ and NMDA‐type receptors, as well as on group I mGlu receptors to induce an increase in astroglial [Ca 2+ ] i . The direct Ca 2+ signal evoked by glutamate was small, and the main action of glutamate was to trigger the release of the “gliotransmitter” ATP by a mechanism involving P2X 7 receptors; propagation of the glutamate‐mediated Ca 2+ signal was significantly reduced in P2X 7 knock‐out mice. Furthermore, axonal action potentials and mechanical stimulation of astrocytes both induced the release of ATP, to propagate Ca 2+ signals in astrocytes and neighboring EGFP‐negative glia. Our data provide a model of multiphase axon–glial signaling in the optic nerve as follows: action potentials trigger axonal release of ATP, which evokes further release of ATP from astrocytes, and this acts by amplifying the initiating signal and by transmitting an intercellular Ca 2+ wave to neighboring glia. © 2008 Wiley‐Liss, Inc.