Isoflurane Depression of Spinal Nociceptive Processing and Minimum Alveolar Anesthetic Concentration Are Not Attenuated in Mice Expressing Isoflurane Resistant Gamma-aminobutyric Acid Type-A Receptors

Overview

Journal Neurosci Lett

Specialty Neurology

Date 2007 Jun 5

PMID 17543455

Citations 4

Authors

Jongbun Kim

Richard Atherley

David F Werner

Gregg E Homanics

Earl Carstens

Joseph F Antognini

Affiliations

Soon will be listed here.

Abstract

Anesthetics produce immobility and depress spinal nociceptive processing, but the exact sites and mechanisms of anesthetic action are unknown. The gamma-aminobutyric acid type-A (GABAA) receptor is thought to be important to anesthetic action. We studied knock-in mice that had mutations in the alpha1 subunit of the GABAA receptor that imparts resistance to isoflurane in in vitro systems. We determined the isoflurane minimum alveolar concentration (MAC) that produces immobility in 50% of subjects and responses of lumbar neurons (single-unit recordings) to noxious stimulation (5 s pinch) of the hindpaw. Isoflurane MAC did not differ between wild-type (1.1+/-0.1%) and knock-in (1.1+/-0.1%) mice. Isoflurane depressed neuronal responses to noxious stimulation (60 s period during and after pinch) similarly in both wild-type and knock-in mice (555+/-133 and 636+/-106 impulses/min, respectively, at 0.8 MAC and 374+/-81 and 409+/-85 impulses/min at 1.2 MAC). We conclude that isoflurane enhancement of alpha1-containing GABAA receptors is not required to produce immobility or depress spinal nociceptive processing.

Citing Articles

Mutations M287L and Q266I in the glycine receptor α1 subunit change sensitivity to volatile anesthetics in oocytes and neurons, but not the minimal alveolar concentration in knockin mice.

Borghese C, Xiong W, Oh S, Ho A, Mihic S, Zhang L Anesthesiology. 2012; 117(4):765-71.

PMID: 22885675 PMC: 3447119. DOI: 10.1097/ALN.0b013e31826a0d93.

Gamma-aminobutyric acid type A receptor alpha 4 subunit knockout mice are resistant to the amnestic effect of isoflurane.

Rau V, Iyer S, Oh I, Chandra D, Harrison N, Eger 2nd E Anesth Analg. 2009; 109(6):1816-22.

PMID: 19923508 PMC: 2895314. DOI: 10.1213/ANE.0b013e3181bf6ae6.

Rat dorsal horn nociceptive-specific neurons are more sensitive than wide dynamic range neurons to depression by immobilizing doses of volatile anesthetics: an effect partially reversed by the opioid receptor antagonist naloxone.

Barter L, Carstens E, Jinks S, Antognini J Anesth Analg. 2009; 109(2):641-7.

PMID: 19608842 PMC: 2760091. DOI: 10.1213/ane.0b013e3181a9770f.

The effects of aromatic anesthetics on dorsal horn neuronal responses to noxious stimulation.

Yao A, Kim J, Atherley R, Jinks S, Carstens E, Shargh S Anesth Analg. 2008; 106(6):1759-64.

PMID: 18499606 PMC: 2670468. DOI: 10.1213/ane.0b013e3181732ee3.

References

Homanics G, Ferguson C, Quinlan J, Daggett J, Snyder K, Lagenaur C . Gene knockout of the alpha6 subunit of the gamma-aminobutyric acid type A receptor: lack of effect on responses to ethanol, pentobarbital, and general anesthetics. Mol Pharmacol. 1997; 51(4):588-96. DOI: 10.1124/mol.51.4.588. View

McKernan R, Whiting P . Which GABAA-receptor subtypes really occur in the brain?. Trends Neurosci. 1996; 19(4):139-43. DOI: 10.1016/s0166-2236(96)80023-3. View

Antognini J, Schwartz K . Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology. 1993; 79(6):1244-9. DOI: 10.1097/00000542-199312000-00015. View

Rampil I, Mason P, Singh H . Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology. 1993; 78(4):707-12. DOI: 10.1097/00000542-199304000-00014. View

Zhang Y, Sonner J, Eger 2nd E, Stabernack C, Laster M, Raines D . Gamma-aminobutyric acidA receptors do not mediate the immobility produced by isoflurane. Anesth Analg. 2004; 99(1):85-90. DOI: 10.1213/01.ANE.0000118108.64886.42. View

Cuellar J, Antognini J, Carstens E . An in vivo method for recording single unit activity in lumbar spinal cord in mice anesthetized with a volatile anesthetic. Brain Res Brain Res Protoc. 2004; 13(2):126-34. DOI: 10.1016/j.brainresprot.2004.03.002. View

Reynolds D, Rosahl T, Cirone J, OMeara G, Haythornthwaite A, Newman R . Sedation and anesthesia mediated by distinct GABA(A) receptor isoforms. J Neurosci. 2003; 23(24):8608-17. PMC: 6740367. View

Sonner J, Antognini J, Dutton R, Flood P, Gray A, Harris R . Inhaled anesthetics and immobility: mechanisms, mysteries, and minimum alveolar anesthetic concentration. Anesth Analg. 2003; 97(3):718-740. DOI: 10.1213/01.ANE.0000081063.76651.33. View

Kralic J, Wheeler M, Renzi K, Ferguson C, OBuckley T, Grobin A . Deletion of GABAA receptor alpha 1 subunit-containing receptors alters responses to ethanol and other anesthetics. J Pharmacol Exp Ther. 2003; 305(2):600-7. DOI: 10.1124/jpet.102.048124. View

10.

Jurd R, Arras M, Lambert S, Drexler B, Siegwart R, Crestani F . General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J. 2002; 17(2):250-2. DOI: 10.1096/fj.02-0611fje. View

11.

Antognini J, Carstens E . In vivo characterization of clinical anaesthesia and its components. Br J Anaesth. 2002; 89(1):156-66. DOI: 10.1093/bja/aef156. View

12.

Kingery W, Agashe G, Guo T, Sawamura S, Davies M, Clark J . Isoflurane and nociception: spinal alpha2A adrenoceptors mediate antinociception while supraspinal alpha1 adrenoceptors mediate pronociception. Anesthesiology. 2002; 96(2):367-74. DOI: 10.1097/00000542-200202000-00023. View

13.

Wong S, Cheng G, Homanics G, Kendig J . Enflurane actions on spinal cords from mice that lack the beta3 subunit of the GABA(A) receptor. Anesthesiology. 2001; 95(1):154-64. DOI: 10.1097/00000542-200107000-00026. View

14.

Mihalek R, Banerjee P, Korpi E, Quinlan J, Firestone L, Mi Z . Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A receptor delta subunit knockout mice. Proc Natl Acad Sci U S A. 1999; 96(22):12905-10. PMC: 23157. DOI: 10.1073/pnas.96.22.12905. View

15.

Rudolph U, Crestani F, Benke D, Brunig I, Benson J, Fritschy J . Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes. Nature. 1999; 401(6755):796-800. DOI: 10.1038/44579. View

16.

Zhang Y, Wu S, Eger 2nd E, Sonner J . Neither GABA(A) nor strychnine-sensitive glycine receptors are the sole mediators of MAC for isoflurane. Anesth Analg. 2001; 92(1):123-7. DOI: 10.1097/00000539-200101000-00024. View

17.

Tobler I, Kopp C, Deboer T, Rudolph U . Diazepam-induced changes in sleep: role of the alpha 1 GABA(A) receptor subtype. Proc Natl Acad Sci U S A. 2001; 98(11):6464-9. PMC: 33491. DOI: 10.1073/pnas.111055398. View

18.

Zhang Y, Stabernack C, Sonner J, Dutton R, Eger 2nd E . Both cerebral GABA(A) receptors and spinal GABA(A) receptors modulate the capacity of isoflurane to produce immobility. Anesth Analg. 2001; 92(6):1585-9. DOI: 10.1097/00000539-200106000-00047. View

19.

Quinlan J, Homanics G, Firestone L . Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor. Anesthesiology. 1998; 88(3):775-80. DOI: 10.1097/00000542-199803000-00030. View

20.

Krasowski M, Harrison N . General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999; 55(10):1278-303. PMC: 2854026. DOI: 10.1007/s000180050371. View