Isoflurane-Induced Changes in Righting Response and Breathing Are Modulated by RGS Proteins

Departments of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109-5615, USA.
Anesthesia and analgesia (Impact Factor: 3.47). 11/2009; 109(5):1500-5. DOI: 10.1213/ANE.0b013e3181ba7815
Source: PubMed


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.
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.
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.
Modulation of G(alpha)(i2) signaling by RGS proteins alters loss and resumption of wakefulness and state-dependent changes in breathing.

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Available from: Xinyan Huang, Mar 05, 2014
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    • "The amnesic effects of isoflurane are mediated, at least in part, throughout enhancement of GABA neurotransmission , since the knockout mice for the a4 subunit of the GABA type A receptor are much more resistant [27]. Other effects of isoflurane such as depression of breathing and righting response appear to be related to changes in other proteins such as regulatory G signalling protein [28]. "
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