title: RGS Proteins and Gαi2 Modulate Sleep, Wakefulness, and Disruption of Sleep/ Wake States after Isoflurane and Sevoflurane Anesthesia.
abstract: OBJECTIVE
  This study tested the hypothesis that Regulators of G protein Signaling (RGS) proteins contribute to the regulation of wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, and to sleep disruption caused by volatile anesthetics.
  
  
  METHODS
  The three groups used in this study included wild-type (WT; n = 7) mice and knock-in mice that were heterozygous (+/GS; n = 7) or homozygous (GS/GS; n = 7) for an RGS-insensitive allele that causes prolonged Gαi2 signaling. Mice were implanted with electrodes for recording sleep and conditioned for 1 week or more to sleep in the laboratory. Using within and between groups designs, 24-h recordings of wakefulness, NREM sleep, and REM sleep were compared across three interventions: (1) baseline (control) and after 3 h of being anesthetized with (2) isoflurane or (3) sevoflurane.
  
  
  RESULTS
  Baseline recordings during the light phase revealed that relative to WT mice, homozygous RGS-insensitive (GS/GS) mice exhibit significantly increased wakefulness and decreased NREM and REM sleep. During the dark phase, these state-specific differences remained significant but reversed direction of change. After cessation of isoflurane and sevoflurane anesthesia there was a long-lasting and significant disruption of sleep and wakefulness. The durations of average episodes of wakefulness, NREM sleep, and REM sleep were significantly altered as a function of genotype and isoflurane and sevoflurane anesthesia.
  
  
  CONCLUSIONS
  RGS proteins and Gαi2 play a significant role in regulating states of wakefulness, NREM sleep, and REM sleep. Genotype-specific differences demonstrate that RGS proteins modulate sleep disruption caused by isoflurane and sevoflurane anesthesia. The results also support the conclusion that isoflurane and sevoflurane anesthesia do not satisfy the homeostatic drive for sleep.
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.|Department of Anesthesiology, The Second Artillery General Hospital, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.
authors.forename: Heather
authors.initials: H
authors.lastname: Wheat
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.
authors.forename: Peter
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.
authors.forename: Sha
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.|Departments of Anesthesiology and Psychology, University of Tennessee, Knoxville, TN.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Baghdoyan
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Neubig
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology, University of Michigan, Ann Arbor, MI.|Departments of Anesthesiology and Psychology, University of Tennessee, Knoxville, TN.
authors.forename: Ralph
authors.initials: R
authors.lastname: Lydic
mesh_terms: D000758:Anesthesia; D000818:Animals; D004567:Electrodes, Implanted; D004569:Electroencephalography; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D020710:RGS Proteins / Q000378:metabolism*; D000077149:Sevoflurane; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology*
chemical_list: D008738:Methyl Ethers; D020710:RGS Proteins; D000077149:Sevoflurane; D007530:Isoflurane; D051960:GTP-Binding Protein alpha Subunit, Gi2
keywords: G proteins; metabotropic receptors; shared circuits hypothesis; signal transduction