Effects of Gaseous Anesthetics Nitrous Oxide and Xenon on Ligand-gated Ion Channels: Comparison with Isoflurane and Ethanol

  title={Effects of Gaseous Anesthetics Nitrous Oxide and Xenon on Ligand-gated Ion Channels: Comparison with Isoflurane and Ethanol},
  author={Tomohiro Yamakura and R. Adron Harris},
BackgroundLigand-gated ion channels are considered to be potential general anesthetic targets. Although most general anesthetics potentiate the function of &ggr;-aminobutyric acid receptor type A (GABAA), the gaseous anesthetics nitrous oxide and xenon are reported to have little effect on GABAA receptors but inhibit N-methyl-d-aspartate (NMDA) receptors. To define the spectrum of effects of nitrous oxide and xenon on receptors thought to be important in anesthesia, the authors tested these… 

The Anesthetic Mechanism of Urethane: The Effects on Neurotransmitter-Gated Ion Channels

At concentrations close to anesthetic 50% effective concentration, urethane had modest effects on all channels tested, suggesting the lack of a single predominant target for its action, which may account for its usefulness as a veterinary anesthetic.

Effects of Anesthetics on Mutant N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes

Alcohols, inhaled anesthetics, and some injectable anesthetics inhibit the function of N-methyl-d-aspartate (NMDA) receptors, but the mechanisms responsible for this inhibition are not fully

Determinants of the Sensitivity of AMPA Receptors to Xenon

AMPA receptors, when assayed in heterologous expression systems, showed a sensitivity to inhalational anesthetics that was minimal when glutamate was applied rapidly at high concentrations, which concludes that AMPA receptors are unlikely to play a major role in the production of the anesthetic state by inhalational agents.

Nitrous Oxide and Xenon Inhibit the Human (&agr;7)5 Nicotinic Acetylcholine Receptor Expressed in Xenopus Oocyte

Results suggest that inhibition of the (&agr;7)5 nACh receptor by N2O and Xe may play a role in their anesthetic effects.

N-Methyl-d-Aspartate Receptor Channel Blocker–Like Discriminative Stimulus Effects of Nitrous Oxide Gas

The results support the hypothesis that the discriminative stimulus effects of N2O are at least partially mediated by NMDA antagonist effects similar to those produced by channel blockers, however, as none of the drugs tested fully mimicked the stimulus results of N 2O, other mechanisms may also be involved.

The Diverse Actions of Volatile and Gaseous Anesthetics on Human-cloned 5-Hydroxytryptamine3 Receptors Expressed in Xenopus Oocytes

Both halothane and isoflurane enhanced 5-HT3 receptor function in a concentration-dependent manner, which is consistent with previous studies and suggests the inhibitory mechanism of sevoflURane might be different from those of N2O and Xe.

Ion Channels in Anesthesia.

The recent advance in understanding the molecular mechanisms underlying anesthesia through the molecular structures of these ligand-gated ion channels is discussed.

GABAA positive modulator and NMDA antagonist-like discriminative stimulus effects of isoflurane vapor in mice

The discriminative stimulus effects of sub-anesthetic concentrations of isoflurane vapor appear to be mediated by both positive allosteric modulation of GABAA receptors as well as antagonism of NMDA receptors.

Protein-Noble Gas Interactions Investigated by Crystallography on Three Enzymes - Implication on Anesthesia and Neuroprotection Mechanisms

Scales that assess the in-vivo potency of inhaled anesthetics in humans are based on the minimum alveolar anesthetic concentrations (MAC) that are associated with well-defined behavioural endpoints that induces the first stages of anesthesia such as amnesia and hypnosis.



Inhibition of rho1 receptor GABAergic currents by alcohols and volatile anesthetics.

  • S. MihicR. Harris
  • Biology
    The Journal of pharmacology and experimental therapeutics
  • 1996
The opposite effects of alcohols and anesthetics on rho1 and GABA(A) receptors, despite their significant amino acid sequence homology, may help in the identification of the particular amino acids responsible for the actions of these compounds on these receptors.

Sites of Volatile Anesthetic Action on Kainate (Glutamate Receptor 6) Receptors*

It is suggested that a specific amino acid, Gly-819, is critical for the action of volatile anesthetics, but not of ethanol or pentobarbital, on the GluR6 receptor.

Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors

Observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetic action.

Effect of Nitrous Oxide on Excitatory and Inhibitory Synaptic Transmission in Hippocampal Cultures

It is found that N2O inhibits both NMDA and non-NMDA receptor-mediated responses to exogenous agonist, and the effects of N2o on synaptic transmission are confined to postsynaptic targets.

Actions of the general anesthetic propofol on recombinant human GABAA receptors: influence of receptor subunits.

The results suggest that propofol exerts a dual effect on GABAA receptors: a positive modulation of the GABA-mediated action on GabAA receptors that is not influenced by the receptor subunit composition, and a specific interaction with the beta-subunit that directly activates the GAB AA receptor-coupled Cl- channel.

Differential Sensitivities of Mammalian Neuronal and Muscle Nicotinic Acetylcholine Receptors to General Anesthetics

Although there is considerable uncertainty about the physiologic roles that neuronal nAChRs play in the central nervous system, their extraordinary sensitivity to general anesthetics, particularly the inhalational agents, suggests they may mediate some of the effects of generalAnesthetics at surgical, or even subanesthetic, concentrations.

Anesthetics produce subunit-selective actions on glutamate receptors.

Results provide novel evidence that anesthetics produce selective actions on glutamate receptors, suggesting that subunit composition may determine the role of glutamate receptors in anesthesia.

Alpha4beta2 Neuronal Nicotinic Acetylcholine Receptors in the Central Nervous System Are Inhibited by Isoflurane and Propofol, but alpha7‐type Nicotinic Acetylcholine Receptors Are Unaffected

The alpha4beta2 receptor is affected by isoflurane more potently than the most sensitive GABAA or glycine receptor that has been reported, whereas the alpha7 homomeric receptor is not affected by either anesthetic.

Contrasting Synaptic Actions of the Inhalational General Anesthetics Isoflurane and Xenon

The authors’ results show that isoflurane and xenon have very different effects on GABAergic and glutamatergic synaptic transmission, and this may account for their differing pharmacologic profiles.

Nitrous Oxide‐induced Enhancement of gamma‐Aminobutyric Acid sub A‐mediated Chloride Currents in Acutely Dissociated Hippocampal Neurons

It is indicated that N2 O can enhance GABA sub A channel‐mediated Cl sup ‐ currents by modulating the effect of the specific GABAA agonist; it is not active by itself.