Isoflurane-induced changes in righting response and breathing are modulated by RGS proteins.

Full Abstract

BACKGROUND: Recent evidence suggests that G protein-coupled receptors, especially those linked to G(alpha)(i), contribute to the mechanisms of anesthetic action. Regulator of G protein signaling (RGS) proteins bind to activated G(alpha)(i) and inhibit signal transduction. Genomic knock-in mice with an RGS-insensitive G(alpha)(i2) G184S (G(alpha)(i2) GS) allele exhibit enhanced G(alpha)(i2) signaling and provide a novel approach for investigating the role of G(alpha)(i2) signaling and RGS proteins in general anesthesia. METHODS: We anesthetized homozygous G(alpha)(i2) GS/GS and wild-type (WT) mice with isoflurane and quantified time (in seconds) to loss and resumption of righting response. During recovery from isoflurane anesthesia, breathing was quantified in a plethysmography chamber for both lines of mice. RESULTS: G(alpha)(i2) GS/GS mice required significantly less time for loss of righting and significantly more time for resumption of righting than WT mice. During recovery from isoflurane anesthesia, G(alpha)(i2) GS/GS mice exhibited significantly greater respiratory depression. Poincaré analyses show that GS/GS mice have diminished respiratory variability compared with WT mice. CONCLUSION: Modulation of G(alpha)(i2) signaling by RGS proteins alters loss and resumption of wakefulness and state-dependent changes in breathing.

Author information

Author/s: Icaza, Eduardo E (EE); Huang, Xinyan (X); Fu, Ying (Y); Neubig, Richard R (RR); Baghdoyan, Helen A (HA); Lydic, Ralph (R);

Affiliation: Departments of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109-5615, USA.

Grants: GM39561 (Agency:NIGMS NIH HHS) ; HL40881 (Agency:NHLBI NIH HHS) ; HL57120 (Agency:NHLBI NIH HHS) ; HL65272 (Agency:NHLBI NIH HHS) ; MH45361 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Anesthesia and analgesia (Anesth Analg), published in United States. (Language: eng)

Reference: 2009-Nov; vol 109 (issue 5) : pp 1500-5

Dates: Created 2009/10/21; Completed 2009/11/05;

PMID: 19843788, status: MEDLINE (last retrieval date: 11/5/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Anesthesia Recovery Period
Anesthetics, Inhalation - pharmacology
Animals
Behavior, Animal - drug effects
Consciousness - drug effects
GTP-Binding Protein alpha Subunit, Gi2 - genetics; metabolism
Gene Knock-In Techniques
Isoflurane - pharmacology
Male

Associated Chemicals: Anesthetics, Inhalation (0) ; RGS Proteins (0) ; Isoflurane (26675-46-7) ; GTP-Binding Protein alpha Subunit, Gi2 (EC 3.6.1.46) ; Gnai2 protein, mouse (EC 3.6.1.46)

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