title: Astrocyte-neuron interaction in the substantia gelatinosa of the spinal cord dorsal horn via P2X7 receptor-mediated release of glutamate and reactive oxygen species.
abstract: The substantia gelatinosa (SG) of the spinal cord processes incoming painful information to ascending projection neurons. Whole-cell patch clamp recordings from SG spinal cord slices documented that in a low Ca(2+) /no Mg(2+) (low X(2+) ) external medium adenosine triphosphate (ATP)/dibenzoyl-ATP, Bz-ATP) caused inward current responses, much larger in amplitude than those recorded in a normal X(2+) -containing bath medium. The effect of Bz-ATP was antagonized by the selective P2X7 receptor antagonist A-438079. Neuronal, but not astrocytic Bz-ATP currents were strongly inhibited by a combination of the ionotropic glutamate receptor antagonists AP-5 and CNQX. In fact, all neurons and some astrocytes responded to NMDA, AMPA, and muscimol with inward current, demonstrating the presence of the respective receptors. The reactive oxygen species H2 O2 potentiated the effect of Bz-ATP at neurons but not at astrocytes. Hippocampal CA1 neurons exhibited a behavior similar to, but not identical with SG neurons. Although a combination of AP-5 and CNQX almost abolished the effect of Bz-ATP, H2 O2 was inactive. A Bz-ATP-dependent and A-438079-antagonizable reactive oxygen species production in SG slices was proven by a microelectrode biosensor. Immunohistochemical investigations showed the colocalization of P2X7-immunoreactivity with microglial (Iba1), but not astrocytic (GFAP, S100β) or neuronal (MAP2) markers in the SG. It is concluded that SG astrocytes possess P2X7 receptors; their activation leads to the release of glutamate, which via NMDA- and AMPA receptor stimulation induces cationic current in the neighboring neurons. P2X7 receptors have a very low density under resting conditions but become functionally upregulated under pathological conditions.
authors.affiliation: Rudolf Boehm Institute for Pharmacology und Toxicology, University of Leipzig, Leipzig, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ficker
authors.forename: Katalin
authors.initials: K
authors.lastname: Rozmer
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Kató
authors.forename: Rómeó D
authors.initials: RD
authors.lastname: Andó
authors.forename: Luisa
authors.initials: L
authors.lastname: Schumann
authors.forename: Ute
authors.initials: U
authors.lastname: Krügel
authors.forename: Heike
authors.initials: H
authors.lastname: Franke
authors.forename: Beáta
authors.initials: B
authors.lastname: Sperlágh
authors.forename: Thomas
authors.initials: T
authors.lastname: Riedel
authors.forename: Peter
authors.initials: P
authors.lastname: Illes
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007150:Immunohistochemistry; D008822:Mice, Transgenic; D008839:Microelectrodes; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism*; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000378:metabolism*; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D058486:Receptors, Purinergic P2X7; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006861:Hydrogen Peroxide
keywords: ATP; P2X7 receptors; amino acid transmitters; astrocytes; neurons; substantia gelatinosa