Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats.

@article{Grasshoff2006EffectsOI,
  title={Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats.},
  author={Christian Grasshoff and Bernd Antkowiak},
  journal={British journal of anaesthesia},
  year={2006},
  volume={97 5},
  pages={
          687-94
        }
}
BACKGROUND Volatile anaesthetics are widely used agents in clinical anaesthesia, although their mechanism of action is poorly understood. In particular, the dominant molecular mechanisms by which volatile anaesthetics depress spinal neurones and thereby mediate spinal effects such as immobility have recently become a matter of dispute. As GABAA and glycine receptors are potential candidates we investigated the impact of both receptor systems in mediating the depressant effects of isoflurane and… 
Opposing Actions of Sevoflurane on GABAergic and Glycinergic Synaptic Inhibition in the Spinal Ventral Horn
TLDR
The hypothesis that the impact of GABAA receptors in mediating the immobilizing properties of volatile anesthetics is less essential in comparison to glycine receptors is supported.
Inhibition of Voltage-Gated Sodium Channels by Emulsified Isoflurane May Contribute to Its Subarachnoid Anesthetic Effect in Beagle Dogs
TLDR
Emulsified isoflurane produced dose-dependent subarachnoid anesthesia, and this effect might be mediated by inhibition of EI on voltage-gated Na+ channels in the spinal cord.
Modulation of Presynaptic β3-Containing GABAA Receptors Limits the Immobilizing Actions of GABAergic Anesthetics
TLDR
The results suggest that the limited immobilizing efficacy of these agents is probably due to a presynaptic mechanism and that GABAergic agents with a specificity for post-versus presynaptically located GABAA receptors would probably have much stronger immobilizing actions, pointing out novel avenues for drug development.
Sevoflurane depresses neurons in the medial parabrachial nucleus by potentiating postsynaptic GABAA receptors and background potassium channels
TLDR
Results indicate that sevoflurane inhibits MPB neurons through postsynaptic GABAA-Rs and background potassium channels, which contributes to sev of lurane-induced hypnosis.
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TLDR
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TLDR
The findings suggest that the hypnotic effects of anaesthetic drugs may be moderately enhanced by gap junction blockade, and that young connexin36 knockout animals remained anaesthetised for longer than young wild‐type mice.
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TLDR
The results suggest that in the spinal ventral horn thiopental acts mostly, but not exclusively, via GABA(A) receptors, and with increasing concentrations of the drug, inhibition via sIPSCs is limited by negative feedback on interneuronal firing whereas action potential-independent GABAergic inhibition due to tonic currents gains progressively in impact.
Daily Isoflurane Exposure Increases Barbiturate Insensitivity in Medullary Respiratory and Cortical Neurons via Expression of ε-Subunit Containing GABA ARs
TLDR
It is hypothesized that increased inhibitory tone in the respiratory control network and cortex causes a compensatory increase in ε-subunit-containing GABAARs.
GABAergic Excitotoxicity Injury of the Immature Hippocampal Pyramidal Neurons' Exposure to Isoflurane
TLDR
Isoflurane-mediated enhancement of GABA-triggered [Ca2+]i release results from membrane depolarization with subsequent activation of VDCCs and further Ca2-induced Ca2+ release from the ryanodine-sensitizing Ca2+.
Comparison of Spinal Anesthetic Effect between Emulsified Isoflurane and Emulsified Nonimmobilizer F6
Background: Our previous study found that emulsified isoflurane (EI) produced subarachnoid anesthesia in dogs. The spinal effect of isoflurane might account for its immobility action. 1,
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References

SHOWING 1-10 OF 34 REFERENCES
Propofol and Sevoflurane Depress Spinal Neurons In Vitro via Different Molecular Targets
TLDR
Evidence is provided that sevoflurane causes immobility by a mechanism distinct from the actions of the intravenous anesthetic propofol, and glycine and GABAA receptors are the most important molecular targets mediating depressant effects of sev ofluranes in the spinal cord.
Effects of Small Concentrations of Volatile Anesthetics on Action Potential Firing of Neocortical Neurons In Vitro
TLDR
Evidence is provided that halothane, isoflurane, and enflurane reduced spontaneous action potential firing of neocortical neurons in cultured brain slices mainly by increasing GABAA‐mediated synaptic inhibition.
Dual actions of volatile anesthetics on GABA(A) IPSCs: dissociation of blocking and prolonging effects.
TLDR
Results show that enflurane, isoflurane and halothane reduce IPSC amplitude through a direct postsynaptic action, suggesting that distinct mechanisms underlie the two actions.
Pre‐ and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons
TLDR
There are opposing facilitatory and inhibitory actions of volatile anaesthetics on glycine release dependent on calcium homeostatic mechanisms and sodium channels respectively and under normal conditions (no TTX) the absolute amount of glycinergic inhibition does not increase.
Glycine receptors mediate part of the immobility produced by inhaled anesthetics.
TLDR
The present in vivo work indicates that antagonism of the glycine receptor with strychnine increases minimum alveolar anesthetic concentration for halothane more than isoflurane and is ofluranes more than cyclopropane, and support the notion that glycine receptors may mediate part of the immobility produced by inhaled anesthetics.
Different actions of general anesthetics on the firing patterns of neocortical neurons mediated by the GABA(A) receptor.
TLDR
Although several anesthetic agents acted nearly exclusively via the GABA(A) receptor, they changed the discharge patterns of cortical neurons in different ways, explained by GABA-mimetic or benzodiazepine-like molecular interactions.
Enflurane Actions on Spinal Cords from Mice That Lack the &bgr;3 Subunit of the GABAA Receptor
TLDR
Similar enflurane sensitivity in spinal cords from −/− and +/+ mice was coupled with a decreased role for GABAA receptors in mediating the actions of en flurane in the former, implying that other anesthetic targets substitute for GabAA receptors.
GABAA Receptor Blockade Antagonizes the Immobilizing Action of Propofol but Not Ketamine or Isoflurane in a Dose-Related Manner
TLDR
It is concluded that GABAA antagonism can influence the ED50 for immobility of propofol and the non-GABAergic anesthetic ketamine, although to a different degree, reflecting physiologic antagonism for ketamine.
General anesthetic actions in vivo strongly attenuated by a point mutation in the GABAA receptor β3 subunit
  • R. Jurd, Margarete Arrasa, +8 authors U. Rudolph
  • Chemistry, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2003
TLDR
It is demonstrated that a single molecular target, and indeed a specific residue (N265) located within the GABAA receptor β3 subunit, is a major determinant of behavioral responses evoked by the intravenous anesthetics etomidate and propofol, whereas volatile anesthetic appear to act via a broader spectrum of molecular targets.
Gamma-Aminobutyric AcidA Receptors Do Not Mediate the Immobility Produced by Isoflurane
TLDR
The view that GABAA receptors do not mediate immobilization for isoflurane is supported, as the increase did not consistently differ among anesthetics and did not correlate with in vitro enhancement of GAB AA receptors by these anesthetic.
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