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.
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/GSmice 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/GSmice exhibited significantly greater respiratory depression. Poincaré analyses show that GS/GSmice 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.
Authors: Brianna L Goldenstein; Brian W Nelson; Ke Xu; Elizabeth J Luger; Jacquline A Pribula; Jenna M Wald; Lorraine A O'Shea; David Weinshenker; Raelene A Charbeneau; Xinyan Huang; Richard R Neubig; Van A Doze Journal: Mol Pharmacol Date: 2009-02-18 Impact factor: 4.436
Authors: Aaron R Muncey; Adam R Saulles; Lauren G Koch; Steven L Britton; Helen A Baghdoyan; Ralph Lydic Journal: Anesthesiology Date: 2010-11 Impact factor: 7.892
Authors: Chelsea Angel; Zachary T Glovak; Wateen Alami; Sara Mihalko; Josh Price; Yandong Jiang; Helen A Baghdoyan; Ralph Lydic Journal: Anesthesiology Date: 2018-05 Impact factor: 7.892
Authors: Hao Zhang; Heather Wheat; Peter Wang; Sha Jiang; Helen A Baghdoyan; Richard R Neubig; X Y Shi; Ralph Lydic Journal: Sleep Date: 2016-02-01 Impact factor: 5.849