title: The volatile anesthetic isoflurane suppresses spontaneous calcium oscillations in vitro in rat hippocampal neurons by activation of adenosine A1 receptors.
abstract: Primary cultures of rat hippocampal neurons were loaded with the Ca(2+)-indicator fluo-3 and studied with a confocal laser microscope. In Mg(2+)-free medium the cultures showed spontaneous synchronized calcium oscillations. These oscillations derived from excitatory signal transmission by N-methyl-D-aspartate and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptors and were modulated by gamma-aminobutyric acid(A) receptors. The oscillations were dose-dependently depressed by adenosine (IC50=2 microM) or by 2-chloro-N6-cyclopentyladenosine a specific adenosine A1 receptor agonist (IC50=40 nM). These effects were reverted by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific adenosine A1 receptor antagonist. The volatile anesthetic isoflurane also depressed these spontaneous calcium oscillations in a dose dependent manner (IC50=0.25 MAC, Minimum Alveolar Concentration). The isoflurane-induced inhibition was partly reversed in 29-38% of the neurons by DPCPX, indicating that the anesthetic activates this receptor possibly by increasing the extracellular concentration of adenosine.
authors.affiliation: Klinik für Anaesthesiologie, der Universität Würzburg, Josef-Schneider Strasse 2, 97080 Würzburg, Germany. ptas@anaesthesie.uni-wuerzburg.de
authors.forename: P W L
authors.initials: PW
authors.lastname: Tas
authors.forename: C
authors.initials: C
authors.lastname: Eisemann
authors.forename: N
authors.initials: N
authors.lastname: Roewer
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D005333:Fetus; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
chemical_list: D000700:Analgesics; D018685:Anesthetics, Inhalation; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D007530:Isoflurane; D000241:Adenosine