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


CONCLUSIONS
Modulation of G(alpha)(i2) signaling by RGS proteins alters loss and resumption of wakefulness and state-dependent changes in breathing.
Departments of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109-5615, USA.
Eduardo E
EE
Icaza
Xinyan
X
Huang
Ying
Y
Fu
Richard R
RR
Neubig
Helen A
HA
Baghdoyan
Ralph
R
Lydic
D000762:Anesthesia Recovery Period; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003243:Consciousness / Q000187:drug effects*; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010991:Plethysmography; D020710:RGS Proteins / Q000378:metabolism*; D020127:Recovery of Function; D012119:Respiration / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D018685:Anesthetics, Inhalation; D020710:RGS Proteins; D007530:Isoflurane; D051960:GTP-Binding Protein alpha Subunit, Gi2; C498016:Gnai2 protein, mouse