title: [Roles of glutamatergic and GABAergic nervous system in hypnotic and analgesic actions of general anesthetics].
abstract: General anesthetic-induced unresponsiveness covers a spectrum of different behavioral components, namely, (1) amnesia, (2) sedation/hypnosis, (3) analgesia, and (4) immobility. At the molecular and cellular level, anesthetic drugs have been shown to have effects on a wide rage of putative targets, such as ligand-gated ion channels (GABA, glycine, NMDA receptors), other ion channels (K+, Na+, Ca2+), and other intracellular functions. This mini-review summarizes recent topics in this research field focusing on NMDA and GABA receptors. Although ketamine blocks NMDA receptors as an open channel blocker, it has been recently shown that ketamine inhibits hyperpolarization-activated cationic currents (J Neurosci 2009) and also enhances GABA-induced currents in alpha6 GABA receptors (J Neurosci 2008). In addition, ketamine (0.5 microM, 24h) produces loss of phenotype of fast-spiking interneurons via NADPH-oxidase (Science 2007). These data suggests that ketamine have multiple molecular targets in hypnotic, analgesic and amnestic actions. Propofol has been shown to enhance two types of GABAergic inhibition: a synaptic form (phasic inhibition) regulating neural excitability via the activation of postsynaptic GABAA receptors by intermittent GABA release from presynaptic terminals ; and a persistent tonic form (tonic inhibition) generated by continuous activation of extrasynaptic GABAA receptors by low concentrations of ambient GABA. However, the roles of tonic inhibition in hypnotic actions of isoflurane and sevoflurane are less clear. In this mini review, the relative contributions of extrasynaptic GABA receptors in behavioral actions of isoflurane and sevoflurane will be discussed.
authors.affiliation: Department of Anesthesiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishikawa
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000768:Anesthesia, General; D018681:Anesthetics, General / Q000494:pharmacology; D004569:Electroencephalography; D055724:Electrophysiological Phenomena; D005971:Glutamates / Q000502:physiology*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007031:Hypothalamus / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008738:Methyl Ethers / Q000494:pharmacology; D018079:Receptors, GABA / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000700:Analgesics; D018681:Anesthetics, General; D005971:Glutamates; D006993:Hypnotics and Sedatives; D008738:Methyl Ethers; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid; D007649:Ketamine; D007530:Isoflurane