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Canadian Journal of Anesthesia/Journal canadien d'anesthésie
Erschienen in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie 2/2011

01.02.2011 | Theme Issue: Mechanisms of Anesthesia

Identification and characterization of anesthetic targets by mouse molecular genetics approaches

verfasst von: Berthold Drexler, MD, Bernd Antkowiak, PhD, Elif Engin, PhD, Uwe Rudolph, MD

Erschienen in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Ausgabe 2/2011

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Abstract

Purpose

It is now generally accepted that proteins are the primary targets of general anesthetics. However, the demonstration that the activity of a protein is altered by general anesthetics at clinically relevant concentrations in vitro does not provide direct evidence that this target mediates pharmacological actions of general anesthetics. Here we report on advances that have been made in identifying the contribution of individual ligand-gated ion channels to defined anesthetic endpoints using molecular mouse genetics.

Principal findings

Gamma-aminobutyric acid (GABA)A receptor subtypes defined by the presence of the α1, α4, α5, β2, and β3 subunits and two-pore domain potassium channels (TASK-1, TASK-3, and TREK) have been discovered to mediate, at least in part, the hypnotic, immobilizing or amnestic actions of intravenous and volatile general anesthetics. Moreover, using tissues from genetically modified mice, specific functions of GABAA receptor subtypes in cortical and spinal neuronal networks were identified.

Conclusion

Genetically modified mice have been very useful for research on mechanisms of anesthesia and have contributed to the functional identification of general anesthetic targets and of the role of these targets in neuronal networks.
Literatur
1.
Krasowski MD, Harrison NL. General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci 1999; 55: 1278-303.CrossRefPubMed
2.
Rudolph U, Crestani F, Benke D, et al. Benzodiazepine actions mediated by specific gamma-aminobutyric acidA receptor subtypes. Nature 1999; 401: 796-800.CrossRefPubMed
3.
McKernan RM, Rosahl TW, Reynolds DS, et al. Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype. Nat Neurosci 2000; 3: 587-92.CrossRefPubMed
4.
Kralic JE, O’Buckley TK, Khisti RT, Hodge CW, Homanics GE, Morrow AL. GABA(A) receptor alpha-1 subunit deletion alters receptor subtype assembly, pharmacological and behavioral responses to benzodiazepines and zolpidem. Neuropharmacol 2002; 43: 685-94.CrossRef
5.
Sur C, Wafford KA, Reynolds DS, et al. Loss of the major GABA(A) receptor subtype in the brain is not lethal in mice. J Neurosci 2001; 21: 3409-18.PubMed
6.
Zeller A, Crestani F, Camenisch I, et al. Cortical glutamatergic neurons mediate the motor sedative action of diazepam. Mol Pharmacol 2008; 73: 282-91.CrossRefPubMed
7.
Brickley SG, Revilla V, Cull-Candy SG, Wisden W, Farrant M. Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance. Nature 2001; 409: 88-92.CrossRefPubMed
8.
Rudolph U, Moehler H. Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics. Annu Rev Pharmacol Toxicol 2004; 44: 475-98.CrossRefPubMed
9.
Rudolph U, Antkowiak B. Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci 2004; 5: 709-20.CrossRefPubMed
10.
Franks NP. General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci 2008; 9: 370-86.CrossRefPubMed
11.
Cheng VY, Martin LJ, Elliott EM, et al. Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate. J Neurosci 2006; 26: 3713-20.CrossRefPubMed
12.
Liao M, Sonner JM, Jurd R, et al. Beta3-containing gamma-aminobutyric acidA receptors are not major targets for the amnesic and immobilizing actions of isoflurane. Anesth Analg 2005; 101: 412-8.CrossRefPubMed
13.
Zeller A, Arras M, Jurd R, Rudolph U. Mapping the contribution of beta3-containing GABAA receptors to volatile and intravenous general anesthetic actions. BMC Pharmacol 2007; 7: 2.CrossRefPubMed
14.
Gallos G, Gleason NR, Zhang Y, et al. Activation of endogenous GABAA channels on airway smooth muscle potentiates isoproterenol-mediated relaxation. Am J Physiol Lung Cell Mol Physiol 2008; 295: L1040-7.CrossRefPubMed
15.
Xiang YY, Wang S, Liu M, et al. A GABAergic system in airway epithelium is essential for mucus overproduction in asthma. Nat Med 2007; 13: 862-7.CrossRefPubMed
16.
Homanics GE, Ferguson C, Quinlan JJ, et al. 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: 588-96.PubMed
17.
Mihalek RM, Banerjee PK, Korpi ER, et al. Attenuated sensitivity to neuroactive steroids in gamma-aminobutyrate type A receptor delta subunit knockout mice. Proc Natl Acad Sci USA 1999; 96: 12905-10.CrossRefPubMed
18.
Quinlan JJ, Homanics GE, Firestone LL. Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor. Anesthesiology 1998; 88: 775-80.CrossRefPubMed
19.
Sandin RH, Enlund G, Samuelsson P, Lennmarken C. Awareness during anaesthesia: a prospective case study. Lancet 2000; 355: 707-11.CrossRefPubMed
20.
Sebel PS, Bowdle TA, Ghoneim MM, et al. The incidence of awareness during anesthesia: a multicenter United States study. Anesth Analg 2004; 99: 833-9.CrossRefPubMed
21.
Orser BA, Mazer CD, Baker AJ. Awareness during anesthesia. CMAJ 2008; 178: 185-8.PubMed
22.
Collinson N, Kuenzi FM, Jarolimek W, et al. Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha5 subunit of the GABAA receptor. J Neurosci 2002; 22: 5572-80.PubMed
23.
Martin LJ, Oh GH, Orser BA. Etomidate targets alpha5 gamma-aminobutyric acid subtype A receptors to regulate synaptic plasticity and memory blockade. Anesthesiology 2009; 111: 1025-35.CrossRefPubMed
24.
Caraiscos VB, Newell JG, You-Ten KE, et al. Selective enhancement of tonic GABAergic inhibition in murine hippocampal neurons by low concentrations of the volatile anesthetic isoflurane. J Neurosci 2004; 24: 8454-8.CrossRefPubMed
25.
Dai S, Perouansky M, Pearce RA. Amnestic concentrations of etomidate modulate GABAA, slow synaptic inhibition in hippocampus. Anesthesiology 2009; 111: 766-73.CrossRefPubMed
26.
Bieda MC, MacIver MB. Major role for tonic GABAA conductances in anesthetic suppression of intrinsic neuronal excitibility. J Neurophysiol 2004; 92: 1658-67.CrossRefPubMed
27.
Caraiscos VB, Elliott EM, You-Ten KE, et al. Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors. Proc Natl Acad Sci USA 2004; 101: 3662-7.CrossRefPubMed
28.
Zarnowska ED, Keist R, Rudolph U, Pearce RA. GABAA receptor alpha5 subunits contribute to GABAA, slow synaptic inhibition in mouse hippocampus. J Neurophysiol 2009; 101: 1179-91.CrossRefPubMed
29.
Rau V, Iyer SV, Oh I, et al. Gamma-aminobutyric acid type A receptor alpha 4 subunit knockout mice are resistant to the amnestic effect of isoflurane. Anesth Analg 2009; 109: 1816-22.CrossRefPubMed
30.
Mihic SJ, Ye Q, Wick MJ, et al. Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature 1997; 389: 385-9.CrossRefPubMed
31.
Borghese CM, Werner DF, Topf N, et al. An isoflurane- and alcohol-insensitive mutant GABA(A) receptor alpha(1) subunit with near-normal apparent affinity for GABA: characterization in heterologous systems and production of knockin mice. J Pharmacol Exp Ther 2006; 319: 208-18.CrossRefPubMed
32.
Sonner JM, Werner DF, Elsen FP, et al. Effect of isoflurane and other potent inhaled anesthetics on minimum alveolar concentration, learning, and the righting reflex in mice engineered to express alpha1 gamma-aminobutyric acid type A receptors unresponsive to isoflurane. Anesthesiology 2007; 106: 107-13.CrossRefPubMed
33.
Werner DF, Blednov YA, Ariwodola OJ, et al. Knockin mice with ethanol-insensitive alpha1-containing gamma-aminobutyric acid type A receptors display selective alterations in behavioral responses to ethanol. J Pharmacol Exp Ther 2006; 319: 219-27.CrossRefPubMed
34.
Belelli D, Callachan H, Hill-Venning C, Peters JA, Lambert JJ. Interaction of positive allosteric modulators with human and Drosophila recombinant GABA receptors expressed in Xenopus laevis oocytes. Br J Pharmacol 1996; 118: 563-76.PubMed
35.
McGurk KA, Pistis M, Belelli D, Hope AG, Lambert JJ. The effect of a transmembrane amino acid on etomidate sensitivity of an invertebrate GABA receptor. Br J Pharmacol 1998; 124: 13-20.CrossRefPubMed
36.
Hill-Venning C, Belelli D, Peters JA, Lambert JJ. Subunit-dependent interaction of the general anaesthetic etomidate with the gamma-aminobutyric acid type A receptor. Br J Pharmacol 1997; 120: 749-56.CrossRefPubMed
37.
Sanna E, Murgia A, Casula A, Biggio G. Differential subunit dependence of the actions of the general anesthetics alphaxalone and etomidate at gamma-aminobutyric acid type A receptors expressed in Xenopus laevis oocytes. Mol Pharmacol 1997; 51: 484-90.PubMed
38.
Belelli D, Lambert JJ, Peters JA, Wafford K, Whiting PJ. The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid. Proc Natl Acad Sci USA 1997; 94: 11031-6.CrossRefPubMed
39.
Pistis M, Belelli D, McGurk K, Peters JA, Lambert JJ. Complementary regulation of anaesthetic activation of human (alpha6beta3gamma2L) and Drosophila (RDL) GABA receptors by a single amino acid residue. J Physiol 1999; 515: 3-18.CrossRefPubMed
40.
Siegwart R, Jurd R, Rudolph U. Molecular determinants for the action of general anesthetics at recombinant alpha(2)beta(3)gamma(2)gamma-aminobutyric acid(A) receptors. J Neurochem 2002; 80: 140-8.CrossRefPubMed
41.
Reynolds DS, Rosahl TW, Cirone J, et al. Sedation and anesthesia mediated by distinct GABA(A) receptor isoforms. J Neurosci 2003; 23: 8608-17.PubMed
42.
Cirone J, Rosahl TW, Reynolds DS, et al. Gamma-aminobutyric acid type A receptor beta 2 subunit mediates the hypothermic effect of etomidate in mice. Anesthesiology 2004; 100: 1438-45.CrossRefPubMed
43.
Jurd R, Arras M, Lambert S, et al. General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J 2003; 17: 250-2.PubMed
44.
Zeller A, Arras M, Lazaris A, Jurd R, Rudolph U. Distinct molecular targets for the central respiratory and cardiac actions of the general anesthetics etomidate and propofol. FASEB J 2005; 19: 1677-9.PubMed
45.
Fritschy JM, Benke D, Mertens S, Oertel WH, Bachi T, Mohler H. Five subtypes of type A gamma-aminobutyric acid receptors identified in neurons by double and triple immunofluorescence staining with subunit-specific antibodies. Proc Natl Acad Sci USA 1992; 89: 6726-30.CrossRefPubMed
46.
Zeller A, Arras M, Jurd R, Rudolph U. Identification of a molecular target mediating the general anesthetic actions of pentobarbital. Mol Pharmacol 2007; 71: 852-9.CrossRefPubMed
47.
Lambert S, Arras M, Vogt KE, Rudolph U. Isoflurane-induced surgical tolerance mediated only in part by beta3-containing GABA(A) receptors. Eur J Pharmacol 2005; 516: 23-7.CrossRefPubMed
48.
O’Hara PJ, Sheppard PO, Thogersen H, et al. The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins. Neuron 1993; 11: 41-52.CrossRefPubMed
49.
Nishikawa K, MacIver MB. Membrane and synaptic actions of halothane on rat hippocampal pyramidal neurons and inhibitory interneurons. J Neurosci 2000; 20: 5915-23.PubMed
50.
Jevtovic-Todorovic V, Todorovic SM, Mennerick S, et al. Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med 1998; 4: 460-3.CrossRefPubMed
51.
Furukawa H, Singh SK, Mancusso R, Gouaux E. Subunit arrangement and function in NMDA receptors. Nature 2005; 438: 185-92.CrossRefPubMed
52.
Mori H, Mishina M. Structure and function of the NMDA receptor channel. Neuropharmacology 1995; 34: 1219-37.CrossRefPubMed
53.
Sucher NJ, Akbarian S, Chi CL, et al. Developmental and regional expression pattern of a novel NMDA receptor-like subunit (NMDAR-L) in the rodent brain. J Neurosci 1995; 15: 6509-20.PubMed
54.
55.
Sato Y, Kobayashi E, Hakamata Y, et al. Chronopharmacological studies of ketamine in normal and NMDA epsilon1 receptor knockout mice. Br J Anaesth 2004; 92: 859-64.CrossRefPubMed
56.
Sato Y, Kobayashi E, Murayama T, Mishina M, Seo N. Effect of N-methyl-D-aspartate receptor epsilon1 subunit gene disruption of the action of general anesthetic drugs in mice. Anesthesiology 2005; 102: 557-61.CrossRefPubMed
57.
Borges K, Dingledine R. AMPA receptors: molecular and functional diversity. Prog Brain Res 1998; 116: 153-70.CrossRefPubMed
58.
Joo DT, Xiong Z, MacDonald JF, et al. Blockade of glutamate receptors and barbiturate anesthesia: increased sensitivity to pentobarbital-induced anesthesia despite reduced inhibition of AMPA receptors in GluR2 null mutant mice. Anesthesiology 1999; 91: 1329-41.CrossRefPubMed
59.
Joo DT, Gong D, Sonner JM, et al. Blockade of AMPA receptors and volatile anesthetics: reduced anesthetic requirements in GluR2 null mutant mice for loss of the righting reflex and antinociception but not minimum alveolar concentration. Anesthesiology 2001; 94: 478-88.CrossRefPubMed
60.
Heurteaux C, Guy N, Laigle C, et al. TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J 2004; 23: 2684-95.CrossRefPubMed
61.
Linden AM, Aller MI, Leppa E, et al. The in vivo contributions of TASK-1-containing channels to the actions of inhalation anesthetics, the alpha(2) adrenergic sedative dexmedetomidine, and cannabinoid agonists. J Pharmacol Exp Ther 2006; 317: 615-26.CrossRefPubMed
62.
Linden AM, Sandu C, Aller MI, et al. TASK-3 knockout mice exhibit exaggerated nocturnal activity, impairments in cognitive functions, and reduced sensitivity to inhalation anesthetics. J Pharmacol Exp Ther 2007; 323: 924-34.CrossRefPubMed
63.
Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP. General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. Proc Natl Acad Sci USA 2008; 105: 8784-9.CrossRefPubMed
64.
Hentschke H, Schwarz C, Antkowiak B. Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and increase of GABAA receptor-mediated inhibition. Eur J Neurosci 2005; 21: 93-102.CrossRefPubMed
65.
Pirker S, Schwarzer C, Wieselthaler A, Sieghart W, Sperk G. GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 2000; 101: 815-50.CrossRefPubMed
66.
Antognini JF, Schwartz K. Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology 1993; 79: 1244-9.CrossRefPubMed
67.
Rampil IJ, Mason P, Singh H. Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology 1993; 78: 707-12.CrossRefPubMed
68.
Kim J, Yao A, Atherley R, Carsten E, Jinks SL, Antognini JF. Neurons in the ventral spinal cord are more depressed by isoflurane, halothane, and propofol than are neurons in the dorsal spinal cord. Anesth Analg 2007; 105: 1020-6.CrossRefPubMed
69.
Jinks SL, Bravo M, Hayes SG. Volatile anesthetic effects on midbrain-elicited locomotion suggest that the locomotor network in the ventral spinal cord is the primary site for immobility. Anesthesiology 2008; 108: 1016-24.CrossRefPubMed
70.
Alvarez FJ, Taylor-Blake B, Fyffe RE, De Blas AL, Light AR. Distribution of immunoreactivity for the beta 2 and beta 3 subunits of the GABAA receptor in the mammalian spinal cord. J Comp Neurol 1996; 365: 392-412.CrossRefPubMed
71.
Gahwiler BH. Organotypic monolayer cultures of nervous tissue. J Neurosci Methods 1981; 4: 329-42.CrossRefPubMed
72.
Gahwiler BH, Capogna M, Debanne D, McKinney RA, Thompson SM. Organotypic slice cultures: a technique has come of age. Trends Neurosci 1997; 20: 471-7.CrossRefPubMed
73.
Christie SB, De Blas AL. GABAergic and glutamatergic axons innervate the axon initial segment and organize GABA(A) receptor clusters of cultured hippocampal pyramidal cells. J Comp Neurol 2003; 456: 361-74.CrossRefPubMed
74.
Brunig I, Scotti E, Sidler C, Fritschy JM. Intact sorting, targeting, and clustering of gamma-aminobutyric acid A receptor subtypes in hippocampal neurons in vitro. J Comp Neurol 2002; 443: 43-55.CrossRefPubMed
75.
Di Cristo G, Wu C, Chattopadhyaya B, et al. Subcellular domain-restricted GABAergic innervation in primary visual cortex in the absence of sensory and thalamic inputs. Nat Neurosci 2004; 7: 1184-6.CrossRefPubMed
76.
Gredell JA, Turnquist PA, Maciver MB, Pearce RA. Determination of diffusion and partition coefficients of propofol in rat brain tissue: implications for studies of drug action in vitro. Br J Anaesth 2004; 93: 810-7.CrossRefPubMed
77.
Benkwitz C, Liao M, Laster MJ, Sonner JM, Eger EI 2nd, Pearce RA. Determination of the EC50 amnesic concentration of etomidate and its diffusion profile in brain tissue: implications for in vitro studies. Anesthesiology 2007; 106: 114-23.CrossRefPubMed
78.
Antkowiak B. In vitro networks: cortical mechanisms of anaesthetic action. Br J Anaesth 2002; 89: 102-11.CrossRefPubMed
79.
Caplan JB, Madsen JR, Schulze-Bonhage A, Aschenbrenner-Scheibe R, Newman EL, Kahana MJ. Human theta oscillations related to sensorimotor integration and spatial learning. J Neurosci 2003; 23: 4726-36.PubMed
80.
Blatow M, Rozov A, Katona I, et al. A novel network of multipolar bursting interneurons generates theta frequency oscillations in neocortex. Neuron 2003; 38: 805-17.CrossRefPubMed
81.
Drexler B, Roether CL, Jurd R, Rudolph U, Antkowiak B. Opposing actions of etomidate on cortical theta oscillations are mediated by different gamma-aminobutyric acid type A receptor subtypes. Anesthesiology 2005; 102: 346-52.CrossRefPubMed
82.
Morgan M, Lumley J, Whitwam JG. Etomidate, a new water-soluble non-barbiturate intravenous induction agent. Lancet 1975; 1: 955-6.CrossRefPubMed
83.
Avramov MN, Husain MM, White PF. The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy. Anesth Analg 1995; 81: 596-602.CrossRefPubMed
84.
Gazdag G, Kocsis N, Tolna J, Ivanyi Z. Etomidate versus propofol for electroconvulsive therapy in patients with schizophrenia. J ECT 2004; 20: 225-9.CrossRefPubMed
85.
Banoub M, Tetzlaff JE, Schubert A. Pharmacologic and physiologic influences affecting sensory evoked potentials: implications for perioperative monitoring. Anesthesiology 2003; 99: 716-37.CrossRefPubMed
86.
Sloan TB. Anesthetic effects on electrophysiologic recordings. J Clin Neurophysiol 1998; 15: 217-26.CrossRefPubMed
87.
Drexler B, Jurd R, Rudolph U, Antkowiak B. Distinct actions of etomidate and propofol at beta3-containing gamma-aminobutyric acid type A receptors. Neuropharmacology 2009; 57: 446-55.CrossRefPubMed
88.
Jia F, Yue M, Chandra D, Homanics GE, Goldstein PA, Harrison NL. Isoflurane is a potent modulator of extrasynaptic GABA(A) receptors in the thalamus. J Pharmacol Exp Ther 2008; 324: 1127-35.CrossRefPubMed
89.
Ying SW, Werner DF, Homanics GE, Harrison NL, Goldstein PA. Isoflurane modulates excitability in the mouse thalamus via GABA-dependent and GABA-independent mechanisms. Neuropharmacology 2009; 56: 438-47.CrossRefPubMed
90.
Nelson LE, Guo TZ, Lu J, Saper CB, Franks NP, Maze M. The sedative component of anesthesia is mediated by GABA(A) receptors in an endogenous sleep pathway. Nat Neurosci 2002; 5: 979-84.CrossRefPubMed
91.
Zecharia AY, Nelson LE, Gent TC, et al. The involvement of hypothalamic sleep pathways in general anesthesia: testing the hypothesis using the GABAA receptor beta3N265M knock-in mouse. J Neurosci 2009; 29: 2177-87.CrossRefPubMed
92.
Grasshoff C, Jurd R, Rudolph U, Antkowiak B. Modulation of presynaptic beta3-containing GABAA receptors limits the immobilizing actions of GABAergic anesthetics. Mol Pharmacol 2007; 72: 780-7.CrossRefPubMed
93.
Grasshoff C, Antkowiak B. Organotypic cultures of spinal cord ventral horn are valuable tools for investigating immobility-related mechanisms in vitro. Anesth Analg 110: 638.
94.
Banks MI, Pearce RA. Dual actions of volatile anesthetics on GABA(A) IPSCs: dissociation of blocking and prolonging effects. Anesthesiology 1999; 90: 120-34.CrossRefPubMed
95.
Drexler B, Jurd R, Rudolph U, Antkowiak B. Dual actions of enflurane on postsynaptic currents abolished by the gamma-aminobutyric acid type A receptor beta3(N265M) point mutation. Anesthesiology 2006; 105: 297-304.CrossRefPubMed
96.
Li GD, Chiara DC, Cohen JB, Olsen RW. Numerous classes of general anesthetics inhibit etomidate binding to gamma-aminobutyric acid type A (GABAA) receptors. J Biol Chem 2010; 285: 8615-20.CrossRefPubMed
97.
Drexler B, Grasshoff C, Rudolph U, Unertl K, Antkowiak B. The GABA(A) receptor family: possibilities for the development of better anesthetics (German). Anaesthesist 2006; 55: 287-95.CrossRefPubMed
98.
Korpi ER, Grunder G, Luddens H. Drug interactions at GABA(A) receptors. Prog Neurobiol 2002; 67: 113-59.CrossRefPubMed
99.
Heldt SA, Ressler KJ. Forebrain and midbrain distribution of major benzodiazepine-sensitive GABAA receptor subunits in the adult C57 mouse as assessed with in situ hybridization. Neuroscience 2007; 150: 370-85.CrossRefPubMed
100.
Olsen RW, Sieghart W. GABA A receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 2009; 56: 141-8.CrossRefPubMed
Metadaten
Titel
Identification and characterization of anesthetic targets by mouse molecular genetics approaches
verfasst von
Berthold Drexler, MD
Bernd Antkowiak, PhD
Elif Engin, PhD
Uwe Rudolph, MD
Publikationsdatum
01.02.2011
Verlag
Springer-Verlag
Erschienen in
Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Ausgabe 2/2011
Print ISSN: 0832-610X
Elektronische ISSN: 1496-8975
DOI
https://doi.org/10.1007/s12630-010-9414-1

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