title: The interaction of noradrenaline with sevoflurane on GABA(A) receptor-mediated inhibitory postsynaptic currents in the rat hippocampus.
abstract: Little is known about the interaction of noradrenaline with volatile anesthetics in inhibitory synaptic transmission. The purpose of the present study was to investigate the interactions of noradrenaline and sevoflurane on inhibitory synaptic transmission mediated by GABA(A) receptors in the rat hippocampus. Pharmacologically isolated GABA(A) receptor-mediated IPSCs were recorded with whole-cell patch-clamp techniques in pyramidal neurons of the CA1 region of rat hippocampal slices. The actions of noradrenaline, noradrenaline analog, sevoflurane, and the interactions of these agents on the frequency and kinetics of spontaneous GABA(A) receptor-mediated IPSCs were studied. Noradrenaline (10 microM) caused an increase in the frequency of action potential-dependent sIPSCs. These effects were completely reversed by the addition of tetrodotoxin (1 microM), suggesting that noradrenaline produces the discharge of GABAergic interneurons innervating on pyramidal cells via adrenoceptors. Although sevoflurane (0.40 mM, 20 min) slightly depressed the amplitude of sIPSCs, sevoflurane significantly prolonged the decay time constant to 451.1 +/- 89.0% of control (n = 9, P < 0.001) without affecting the rise time. In addition, sevoflurane increased the frequency of sIPSCs up to 3-fold. However, pretreatment of cadmium, multiple Ca channel blocker, abolished sevoflurane effects on the frequency whereas the effects on the decay were still observed. Application of both noradrenaline and sevoflurane produced a significant increase of the IPSC frequency than that of noradrenaline alone or sevoflurane alone with prolonged decays. These results provide evidence that both agents have additive effects on GABAergic synaptic transmission at the central nervous system via different mechanisms.
authors.affiliation: Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi City 371-8511, Japan. nishikaw@med.gunma-u.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kubo
authors.forename: Junko
authors.initials: J
authors.lastname: Ishizeki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Takazawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Fumio
authors.initials: F
authors.lastname: Goto
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D000077149:Sevoflurane; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D008738:Methyl Ethers; D011963:Receptors, GABA-A; D002104:Cadmium; D000077149:Sevoflurane; D009638:Norepinephrine