title: Early adenosine release contributes to hypoxia-induced disruption of stimulus-induced sharp wave-ripple complexes in rat hippocampal area CA3.
abstract: We investigated the effects of hypoxia on sharp wave-ripple complex (SPW-R) activity and recurrent epileptiform discharges in rat hippocampal slices, and the mechanisms underlying block of this activity. Oxygen levels were measured using Clark-style oxygen sensor microelectrodes. In contrast to recurrent epileptiform discharges, oxygen consumption was negligible during SPW-R activity. These network activities were reversibly blocked when oxygen levels were reduced to 20% or less for 3 min. The prolongation of hypoxic periods to 6 min caused reversible block of SPW-Rs during 20% oxygen and irreversible block when 0% oxygen (anoxia) was applied. In contrast, recurrent epileptiform discharges were more resistant to prolonged anoxia and almost fully recovered after 6 min of anoxia. SPW-Rs were unaffected by the application of 1-butyl-3-(4-methylphenylsulfonyl) urea, a blocker of KATP channels, but they were blocked by activation of adenosine A1 receptors. In support of a modulatory function of adenosine, the amplitude and incidence of SPW-Rs were increased during application of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Interestingly, hypoxia decreased the frequency of miniature excitatory post-synaptic currents in CA3 pyramidal cells, an effect that was converted into increased frequency by the adenosine A1 agonist DPCPX. In addition, DPCPX also delayed the onset of hypoxia-mediated block of SPW-Rs. Our data suggest that early adenosine release during hypoxia induces a decrease in pre-synaptic glutamate release and that both might contribute to transient block of SPW-Rs during hypoxia/anoxia in area CA3.
authors.affiliation: Institute for Neurophysiology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Marlene S
authors.initials: MS
authors.lastname: Jarosch
authors.affiliation: Institute for Neurophysiology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Gebhardt
authors.affiliation: Institute for Neurophysiology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fano
authors.affiliation: Institute for Neurophysiology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Huchzermeyer
authors.affiliation: Institute for Neurophysiology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Ul Haq
authors.affiliation: Institute for Neurophysiology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Behrens
authors.affiliation: Institute for Neurophysiology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.|Excellence Cluster NeuroCure, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinemann
mesh_terms: D000241:Adenosine / Q000378:metabolism; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D011810:Quinoxalines; D014970:Xanthines; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; C051360:1,3-dipropyl-8-cyclopentylxanthine; D014633:Valine; D000241:Adenosine; D010100:Oxygen; D001640:Bicuculline
keywords: adenosine A1 receptor; brain slice; oxygen consumption; recurrent epileptiform discharges