| Title | Isoflurane-induced changes in righting response and breathing are modulated by RGS proteins. | | Author(s) | Icaza EE, Huang X, Fu Y, Neubig RR, Baghdoyan HA, Lydic R | | Institution | Departments of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109-5615, USA. | | Source | Anesth Analg 2009 Nov; 109(5):1500-5. | | MeSH | Anesthesia Recovery Period
Anesthetics, Inhalation
Animals
Behavior, Animal
Consciousness
GTP-Binding Protein alpha Subunit, Gi2
Gene Knock-In Techniques
Isoflurane
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Plethysmography
RGS Proteins
Recovery of Function
Respiration
Signal Transduction
Time Factors
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19843788 |
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