Effect of Isoflurane and Other Potent Inhaled Anesthetics on Minimum Alveolar Concentration, Learning, and the Righting Reflex in Mice Engineered to Express α1 γ-Aminobutyric Acid Type A Receptors Unresponsive to Isoflurane

@article{Sonner2007EffectOI,
  title={Effect of Isoflurane and Other Potent Inhaled Anesthetics on Minimum Alveolar Concentration, Learning, and the Righting Reflex in Mice Engineered to Express $\alpha$1 $\gamma$-Aminobutyric Acid Type A Receptors Unresponsive to Isoflurane},
  author={James M. Sonner and David F. Werner and Frank Elsen and Yilei Xing and Mark Liao and R. Adron Harris and Neil L. Harrison and Michael S. Fanselow and Edmond I. Eger and Gregg E. Homanics},
  journal={Anesthesiology},
  year={2007},
  volume={106},
  pages={107-113}
}
Background:Enhancement of the function of γ-aminobutyric acid type A receptors containing the α1 subunit may underlie a portion of inhaled anesthetic action. To test this, the authors created gene knock-in mice harboring mutations that render the receptors insensitive to isoflurane while preserving sensitivity to halothane. Methods:The authors recorded miniature inhibitory synaptic currents in hippocampal neurons from hippocampal slices from knock-in and wild-type mice. They also determined the… 
Isoflurane depression of spinal nociceptive processing and minimum alveolar anesthetic concentration are not attenuated in mice expressing isoflurane resistant γ-aminobutyric acid type-A receptors
TLDR
It is concluded that isoflurane enhancement of alpha1-containing GABAA receptors is not required to produce immobility or depress spinal nociceptive processing.
Inhaled Anesthetic Responses of Recombinant Receptors and Knockin Mice Harboring α2(S270H/L277A) GABAA Receptor Subunits That Are Resistant to Isoflurane
TLDR
Isoflurane produced immobility and amnesia in both wild-type and mutant mice, and potencies did not differ between the strains for these actions of isoflurane, indicating that immobilities or amnesia does not require isofLurane potentiation of the α2 subunit.
Isoflurane Potentiation of GABAA Receptors Is Reduced but Not Eliminated by the β3(N265M) Mutation
TLDR
Compared to the complete insensitivity of β3(N265M) mutant receptors to etomidate and propofol, the mutation has only a partial effect on receptor modulation by isoflurane, which does not exclude a possible contribution of α5β3γ2L GABAA receptors.
Mutations M287L and Q266I in the Glycine Receptor &agr;1 Subunit Change Sensitivity to Volatile Anesthetics in Oocytes and Neurons, but Not the Minimal Alveolar Concentration in Knockin Mice
TLDR
Results indicate that glycine receptors containing the &agr;1 subunit are not likely to be crucial for the action of isoflurane and other VAs.
Genetic reduction of GABAA receptor γ2 subunit expression potentiates the immobilizing action of isoflurane
TLDR
Investigation of the immobilizing action of the volatile anesthetic isoflurane in mice with double knockout (DKO) of phospholipase C-related inactive protein (PRIP)-1 and -2 suggests that reduced expression of the GABA(A) receptor gamma2 subunit affects the composition and function of spinal GABA( A) receptors and potentiates the immobilization action of isofLurane.
Propofol and Isoflurane Enhancement of Tonic Gamma-Aminobutyric Acid Type A Current in Cardiac Vagal Neurons in the Nucleus Ambiguus
  • X. Wang
  • Medicine
    Anesthesia and analgesia
  • 2009
TLDR
It is demonstrated that the general anesthetics propofol and isoflurane enhance both phasic and tonic GABAA receptor-mediated inhibition of CVNs.
GABAA positive modulator and NMDA antagonist-like discriminative stimulus effects of isoflurane vapor in mice
TLDR
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.
Isoflurane modulates excitability in the mouse thalamus via GABA-dependent and GABA-independent mechanisms
TLDR
It is concluded that isoflurane enhances inhibition of thalamic neurons in VB via GABA(A)-R-dependent, but in RTN via GABA-A-R-independent, mechanisms.
Pharmacology of Inhaled Anesthetics
Abstract Inhaled anesthetics as single agents provide all of the essential features of general anesthesia, including amnesia, unconsciousness, and immobility. Each of these components results from
Altered Anesthetic Sensitivity of Mice Lacking Ndufs4, a Subunit of Mitochondrial Complex I
TLDR
Changes in anesthetic sensitivity in a knockout mouse with reduced complex I function due to inactivation of the Ndufs4 gene are the largest recorded in a mammal.
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TLDR
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α1 Subunit-Containing GABA Type A Receptors in Forebrain Contribute to the Effect of Inhaled Anesthetics on Conditioned Fear
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  • Chemistry, Medicine
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  • 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.
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TLDR
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Effects of Isoflurane on &ggr;-Aminobutyric Acid Type A Receptors Activated by Full and Partial Agonists
TLDR
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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.
Mouse strain modestly influences minimum alveolar anesthetic concentration and convulsivity of inhaled compounds.
TLDR
Absence of the neural form of protein kinase C increases minimum alveolar anesthetic concentration for isoflurane, indicating that protein phosphorylation by the gamma-isoform of protein Kinase C (PKCgamma) can influence the potency of this anesthetic.
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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.
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