Abstract
Since their introduction 150 yr ago, volatile anesthetics have revolutionized the practice of medicine. However, it is not clearly understood how the volatile anesthetics produce any of their most profound effects: loss of consciousness, amnesia, and lack of perception of pain. This uncertainty is greatly accentuated by the large number of potential targets that are affected by volatile anesthetics (1,2,3).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Franks, N. P. and Lieb, W. R. (1994) Molecular and cellular mechanisms of general anaesthesia. Nature 367, 607–614.
Kayser, E.-B., Morgan, P. G., and Sedensky, M. M. (1999) GAS-1: A mitochondrial protein controls sensitivity to volatile anesthetics in C. elegans. Anesthesiology 90, 545–554.
van Swinderen, B., Saifee, O., Shebester, L., Roberson, R., Nonet, M. L., and Crowder, C. M. (1999) A neomorphic syntaxin mutation blocks volatile-anesthetic action in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 96 (5), 2479–2484.
Tanifuji, Y., Eger, E. I., II, and Terrell, R. C. (1977) Some characteristics of an exceptionally potent inhaled anesthetic: Thiomethoxyflurane. Anesth. Analg. 56, 387–391.
Koblin, D. D. (2000a) In Anesthesia, Mechanisms of Action, (Miller, R. D., ed.) Churchill Livingstone, New York, pp. 48–73.
Morgan, P. G., Sedensky, M. M., and Meneely, P. M. (1990) Multiple sites of action of volatile anesthetics in Caenorhabditis elegans. PNAS 87, 2965–2968.
Baker, R., Melchior, C., and Deitrich, R. (1980) The effect of halothane on mice selectively bred for differential sensitivity to alcohol. Pharmacol. Biochem. Behay. 12, 691–695.
Koblin, D. D. and Deady, J. E. (1981) Anaesthetic requirement in mice selectively bred for differences in ethanol Sensitivity. Brit. J. Anaesth. 53, 5–10.
Simpson, V. J., Baker, R. C., and Timothy, B. S. (1993) Isoflurane but not halothane demonstrates diffential sleep time in long sleep and short sleep mice. Anesthesiology 79 (3A), A387.
Krishnan, K. S. and Nash, H. A. (1990) A genetic study of the anesthetic response: Mutants of Drosophila melanogaster altered in sensitivity to halothane. Proc. Natl. Acad. Sci. USA 87, 8632–8636.
Gamo, S., Ogaki, M., and Nakashima-Tanaka, E. (1981) Strain differences in minimum anesthetic concentrations in Drosophila melanogaster. Anesthesiology 54, 289–291.
Maclver, M. B. and Kendig, J. J. (1991) Anesthetic effects on resting membrane potential are voltage-dependent and agent-specific. Anesthesiology 74, 83–88.
Sonner, J. M., Gong, D., and Eger, E. I., 2nd. (2000) Naturally occurring variability in anesthetic potency among inbred mouse strains. Anesth. Analg. 91, 720–726.
Zhang, Y., Wu, S., Eger, E. I., 2“d, and Sonner, J. M. (2001) Neither GABAA nor strychnine-sensitive glycine receptors are the sole mediators of MAC for isoflurane. Anesth. Analg. 92, 123–127.
Yamakura, T. and Harris, R. A. (2000) Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol. Anesthesiology 2000 93, 1095–1101.
Urban, B. W. and Friederich, P. (1998) Anesthetic mechanisms in-vitro and in general anesthesia. Toxicol. Lett. 100–101, 9–16.
van Swinderen, B., Metz, L. B., Shebester, L. D., Mendel, J. E., Sternberg, P. W., and Crowder, C. M. (2001) Goalpha regulates volatile anesthetic action in Caenorhabditis elegans. Genetics 158, 643–655.
Oliver, S. G. (1997) From gene to screen with yeast. Curr. Opin. Genet. Dev. 7, 405–409.
Wilson, R. K. (1999) How the worm was won. The C. elegans genome sequencing project. Trends Genet. 15, 51–58.
Celniker, S. E. (2000) The Drosophila genome. Curr. Opin. Genet. Del). 10, 612–616.
Lander, E. S., et al. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860–921.
Clark, M. S. (1999) Comparative genomics: the key to understanding the Human Genome Project. Bioessays 21, 121–130.
No author listed. (2001) Harvesting the fruits of the human genome. Nat. Genet. 27, 227, 228.
Keil, R. L., Wolfe, D., Reiner, T., Peterson, C. J., and Riley, J. L. (1996) Molecular genetic analysis of volatile anesthetic action. Mol. Cell. Biol. 16, 3446–3453.
Wolfe, D., Hester, P., and Keil, R. L. (1998) Volatile anesthetic additivity and specificity in Saccharomyces cerevisiae. Anesthesiology 89, 174–181.
Wolfe, D., Reiner, T., Keeley, J. L., Pizzini, M., and Keil, R. L. (1999) Ubiquitin metabolism affects cellular response to volatile anesthetics in yeast. Mol. Cell. Biol. 19, 8254–8262.
Lafont, F., Verkade, P., Galli, T., et al. (1999) Raft association of SNAP receptors acting in apical trafficking in Madin-Darby canine kidney cells. Proc. Natl. Acad. Sci. USA 96, 3734–3768.
Brenner, S. (1974) The genetics of Caenorhabditis elegans. Genetics 77, 71–94.
Herman, R. K. (1988) Genetics of C. elegans. The Nematode Caenorhabditis elegans. (Wood, W. B., ed.) ( Cold Spring Harbor, Cold Spring Harbor Laboratory Press ) pp. 22–33.
Sulston, J. E. and Horvitz, H. R. (1977) Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dey. Biol. 56, 110–156.
Sulston, J. E., Schierenberg, E., White, J. G., and Thomson, J. N. (1983) The embryonic cell lineage of the nematode, Caenorhabditis elegans. Del). Biol. 100, 64–119.
White, J. G., Southgate, E., Thomson, J. N., and Brenner, S. (1986) The structure of the nervous system in Caenorhabditis elegans. Philos. Trans. Roy. Soc. Lond. 314B, 1–340.
No authors listed. (1998) The genomic sequence of C. elegans. Science 282, 2012–2018.
Morgan, P. G., Sedensky, M. M., Meneely, P. M., and Cascorbi, H. F. (1988) The effect of two genes on anesthetic response in the nematode Caenorhabditis elegans. Anesthesiology 69, 246–251.
Crowder, C. M., Shebester, L. D., and Schedi, T. (1996) Behavioral effects of volatile anesthetics in Caenorhabditis elegans. Anesthesiology 85, 901–912.
Morgan, P. G and Cascorbi, H. F. (1985) Effect of Anesthetics and a Convulsant on Normal and Mutant Caenorhabditis elegans. Anesthesiology 62, 738–744.
van Swinderen, B., Saifee, O., Shebester, L., Roberson, R., Nonet, M. L., and Crowder, C. M. (1999) A neomorphic syntaxin mutation blocks volatile-anesthetic action in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 96, 2479–2484.
Kayser, B., Rajaram, S., Thomas, S., Morgan, P. G., and Sedensky, M. M. (1998) Control of anesthetic response in C. elegans. Toxicol. Lett. 100–101, 339–346.
Koblin, D. D., Chortkoff, B. S., Laster, M. J., Eger, E. I., 2nd, Halsey, M. J., and Ionescu, P. (1994) Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth. Analg. 79, 1043–1048.
Morgan, P. G., Radke, G. W., and Sedensky, M. M. (2000) Effects of Nonimmobilizers and Halothane on Caenorhabditis elegans. Anesth. Analg. 91, 1007–1012.
Morgan, P. G, Usiak, M., and Sedensky, M. M. (1996) Genetic differences affecting the potency of stereoisomers of isoflurane. Anesthesiology 85, 385–392.
Sedensky, M. M. and Meneely, P. M. (1987) Genetic analysis of halothane sensitivity in C. elegans. Science 236, 952–954.
Morgan, P. G, Sedensky, M. M., and Meneely, P. M. (1990) Multiple sites of action of volatile anesthetics in C. elegans. Proc. Natl. Acad. Sci. USA 87, 2965–2969.
Park, E. C. and Horvitz, H. R. (1986) Mutations with dominant effects on the behavior and morphology of the nematode Caenorhabditis elegans. Genetics 113, 821–852.
Rajaram, S., Spangler, T. L., Sedensky, M. M., and Morgan, P. G. (1999) A Stomatin and a Degenerin Interact to Control Anesthetic Sensitivity in C. elegans. Genetics 153, 1673–1682.
Rajaram, S., Sedensky, M. M., Morgan, P. G. (1998) A stomatin homologue controls sensitivity to volatile anesthetics in C. elegans. Proc. Natl. Acad. Sci. USA 95, 8761–8766.
Stewart, G. W., Argent, A. C., and Dash, B. C. J. (1993) Stomatin: a putative cation transport regulator in red cell membrane. Biochim. Biophys. Acta 1225, 15–25.
Stewart, G. W., et al. (1992) Isolation of eDNA coding for a ubiquitous membrane protein deficient in high NA’, low K’, stomatocytic erythrocytes. Blood 79, 1593–1601.
Mannsfeldt, A. G., Carroll, P., Stucky, C., et al. (1999) Stomatin, a MEC-2-like protein, is expressed by mammalian sensory neurons. Molec. Cell Neurosci. 13, 391–404.
Chalfie, M., Tu, Y., Euskirchen, G., Ward, W. W., and Prasher, D. C. (1994) Green fluorescent protein as a marker for gene expression. Science 263, 802–805.
Sedensky, M. M, Siefker, J. M., Morgan, P. G. (2001) Stomatin homologues interact in Caenorhabditis elegans. Am..1. Physiol. Cell Physiol. 280, C1340—C1348.
Tavernarakis, N., Shreffler, W., Wang, S., and Driscoll, M. (1997) unc-8, a DEG/ENaC family member, encodes a subunit of a candidate mechanically gated channel that modulates C. elegans locomotion. Neuron 18, 107–119.
Phelan, P., Bacon, J. P., Davies, J. A., et al. (1998) Innexins: a family of invertebrate gap-junction proteins. Trends Genet. 14(9), 348, 349.
Lipardi, C., Nitsch, L., and Zurzolo, C. (2000) Detergent-insoluble GPI-anchored proteins are apically sorted in Fischer rat thyroid cells, but interference with cholesterol or sphingolipids differentially affects detergent insolubility and apical sorting. Mol. Biol. Cell 11, 531–542.
Hooper, N. M. (1999) Detergent-insoluble glycosphigolipid/cholesterol-rich membrane domains, lipid rafts and caveolae. Molec. Emb. Biol. 16, 145–156.
Snyers, L., Umlauf, E., and Prohaska, R. (1999) Association of stomatin with lipid-protein complexes in the plasma membrane and the endocytic compartment. Eur. J. Cell Biol. 78, 802–812.
Moffett, S,. Brown, D. A., and Linder, M. E. (2000) Lipid-dependent targeting of G proteins into rafts. J. Biol. Chem. 275, 2191–2198.
Morgan, P. G. and Sedensky, M. M. (1994) Mutations conferring new patterns of sensitivity to volatile anesthetics in C. elegans. Anesthesiology 81, 888–898.
Kayser, E.-B., Morgan, P. G., and Sedenskym, M. M. (1999) GAS-1: A mitochondrial protein controls sensitivity to volatile anesthetics in C. elegans. Anesthesiology 90, 545–554.
Kayser, E. B., Morgan, P. G., Hoppel, C. L., and Sedensky, M. M. (2001) Mitochondrial Expression and Function of GAS-1 in Caenorhabditis elegans. J. Biol. Chem. 122, 1187–1201.
Ishii, N., Fujii, M., Hartman, P. S., et al. (1998) A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394, 694–697.
Hartman, P. S., Ishii, N., Kayser, E. B., Morgan, P. G., and Sedensky, M. M. (2001) Varied phenotypes caused by mutations altering mitochondrial complex I or complex II subunits in Caenorhabditis elegans. Mech. Aging Dev. In Press.
Cohen, P. J. (1973) Effects of anesthetics on mitochondrial function. Anesthesiology 39, 153–164.
Harris, R. A., Munroe, J., Farmer, B., Kim, K. C., and Jenkins, P. (1971) Action of halothane upon mitochondrial respiration. Arch. Biochem. Biophys. 142, 435–444.
Morgan, P. G., Hoppel, C. L., and Sedensky, M. M. (2002) Mitochondrial defects and anesthetic sensitivity. Anesthesiology 96, 1268–1269.
Koushika, S. P. and Nonet, M. L. (2000) Sorting and transport in C. elegans: A model system with a sequenced genome. Curr. Opin. Cell Biol. 12, 517–523.
Rand, J. B. and Nonet, M. L. (1997) Synaptic Transmission. in C. elegans II. ( Riddle, D. L., Blumenthal, T., Meyer, B. J., and Priess, J. R., eds.) Cold Spring Harbor, Cold Spring Harbor Laboratory Press, pp. 611–643.
Crowder, C. M. and Berilgen, J. (2000) Isoflurane Binds the Rat Synaptic Protein SNAP-25 at Clinical Concentrations. Anesthesiology A806.
Qi, J., Peters, K. W., Liu, C., Wang, J. M., Edinger, R. S., Johnson, J. P., Watkins, S. C., and Frizzell, R. A. (1999) Regulation of the amiloride-sensitive epithelial sodium channel by syntaxin 1A. J. Biol. Chem. 274, 30,345–30, 348.
Plant, P. J., Lafont, F., Lecat, S., Verkade, P., Simons, K., and Rotin, D. (2000) Apical membrane targeting of Nedd4 is mediated by an association of its C2 domain with annexin XIIIb. J. Cell Biol. 149, 1473–1484.
Gamo, S., Ogaki, M., and Nakashima-Tanaka, E. (1981) Strain differences in minimum anesthetic concentrations in Drosophila melanogaster. Anesthesiology 54, 289–293.
Gamo, S., Dodo, K., Matakatsu, H., and Tanaka, Y. (1998) Molecular genetical analysis of Drosophila ether sensitive mutants. Toxicol. Lett. 100–101, 329–337.
Krishnan, K. S. and Nash, H. A. (1990) A genetic study of the anesthetic response: mutants of Drosophila melanogaster altered in sensitivity to halothane. Proc. Natl. Acad. Sci. USA 87, 8632–8636.
Campbell, D. B. and Nash, H. A. (1994) Use of Drosophila mutants to distinguish among volatile general anesthetics. Proc. Natl. Acad. Sci. USA 91, 2135–2139.
Madhavan, M. C., Kumar, R. A., and Krishnan, K. S. (2000) Genetics of anesthetic response: autosomal mutations that render Drosophila resistant to halothane. Pharmacol. Biochem. Behay. 67, 749–757.
Guan, Z., Scott, R. L., and Nash, H. A. (2000) A new assay for the genetic study of general anesthesia in Drosophila melanogaster: use in analysis of mutations in the X-chromsomal 12E region. J. Neurogen. 14, 25–42.
Campbell, J. L. and Nash, H. A. (1998) The visually induced jump response of Drosophila melangaster is sensitive to volatile anesthetics. J. Neurogen. 12, 241–251.
Walcourt, A. and Nash, H. A. (2000) Genetic effects on an anesthetic sensitive pathway in the brain of Drosophila. J. Neurobiol. 42, 69–78.
Nishikawa, K. and Kidokoro, Y. (1999) Halothane presynaptically depresses synaptic transmission in wild-type Drosophila larvae but not in halothane-resistant (har) mutants. Anesthesiology 90, 1691–1697.
Walcourt, A., Scott, R. L., and Nash, H. A. (2001) Blockage of one class of potassium channel alters the effectiveness of halothane in a brain circuit of Drosophila. Anesth. Analg. 92, 535–541.
Sonner, J. M., Gong, D., Li, J., Eger, E. I., 2nd, and Laster, M. J. (1999) Mouse strain modestly influences minimum alveolar anesthetic concentration and convulsivity of inhaled compounds. Anesth. Analg. 89, 1030–1034.
Sonner, J. M., Gong, D., Eger, and E. I., 2°d. (2000) Naturally occurring variability in anesthetic potency among inbred mouse strains. Anesth. Analg. 91, 720–726.
Demarest, K., McCaughran, J., Jr., Mahjubi, E., Cipp, L., and Hitzemann, R. (1999) Identification of an acute ethanol response quantitative trait locus on mouse chromosome 2. J. Neurosci. 19, 549–561.
Browman, K. E. and Crabbe, J. C. (2000) Quantitative trait loci affecting ethanol sensitivity in BXD recombinant inbred mice. Alcoh. Clin. Exp. Res. 24, 17–23.
Hood, H. M. and Buck, K. J. (2000) Allelic variation in the GABA A receptor gamma2 subunit is associated with genetic susceptibility to ethanol-induced motor incoordination and hypothermia, conditioned taste aversion, and withdrawal in BXD/Ty recombinant inbred mice. Alcoh. Clin. Exp. Res. 24, 1327–1334.
Hanania, T., Negri, C. A, Dunwiddie, T. V., and Zahniser, N. R. (2000) N-methyl-o-aspartate receptor responses are differentially modulated by noncompetitive receptor antagonists and ethanol in inbred long-sleep and short-sleep mice: behavior and electrophysiology. Alcoh. Clin. Exp. Res. 24, 1750–1758.
Erwin, V. G., Heston, W. D., McClearn, G. E., and Deitrich, R. A. (1976) Effect of hypnotics on mice genetically selected for sensitivity to ethanol. Pharmacol. Biochem. Behay. 4, 679–683.
Firestone, L. L., Korpim, E. R., Niemi, L., Rosenberg, P. H., Homanics, G. E., and Quinlan, J. J. (2000) Halothane and desflurane requirements in alcohol-tolerant and -nontolerant rats. Brit. J. Anaesth. 85, 757–762.
Quinlan, J. J., Homanics, G. E., and Firestone, L. L. (1998) Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor. Anesthesiology 88, 775–780.
Ugarte, S. D., Homanics, G. E., Firestone, L. L., and Hammond, D. L. (2000) Sensory thresholds and the antinociceptive effects of GABA receptor agonists in mice lacking the beta3 subunit of the GABA, receptor. Neuroscience 95, 795–806.
Homanics, G. E., Ferguson, C., Quinlan, J. J., et al. (1997) Gene knockout of the alpha6 subunit of the gammaaminobutyric acid type A receptor: lack of effect on responses to ethanol, pentobarbital, and general anesthetics. Mol. Pharmacol. 51, 588–596.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Morgan, P.G., Sedensky, M. (2003). Simple Genetic Models for Anesthetic Action. In: Antognini, J.F., Carstens, E., Raines, D.E. (eds) Neural Mechanisms of Anesthesia. Contemporary Clinical Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-322-4_14
Download citation
DOI: https://doi.org/10.1007/978-1-59259-322-4_14
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-294-0
Online ISBN: 978-1-59259-322-4
eBook Packages: Springer Book Archive