The volatile anesthetic isoflurane suppresses spontaneous calcium oscillations in vitro in rat hippocampal neurons by activation of adenosine A1 receptors.
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.
Tas
P W L
PW
Klinik für Anaesthesiologie, der Universität Würzburg, Josef-Schneider Strasse 2, 97080 Würzburg, Germany. ptas@anaesthesie.uni-wuerzburg.de
Eisemann
C
C
Roewer
N
N
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*
D000700:Analgesics; D018685:Anesthetics, Inhalation; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D007530:Isoflurane; D000241:Adenosine