Der Anaesthesist

, Volume 58, Issue 11, pp 1144–1149

Was wissen wir über Narkosemechanismen?

Bewusstlosigkeit, Bewegungslosigkeit und Amnesie
Klinische Pharmakologie


Während der letzten Jahrzehnte verzeichnete die anästhesiologische Grundlagenforschung einen enormen Wissenszuwachs. Trotz neuer Erkenntnisse auf molekularer Ebene sind die Mechanismen, die Narkose vermitteln, weiterhin nicht vollständig geklärt. Der folgende Beitrag liefert einen knappen Überblick über einige anästhetikasensitive Ionenkanäle und ihre Modulation durch die klinisch gebräuchlichen Anästhetika Isofluran, Propofol und Ketamin. Die Teilaspekte der Allgemeinanästhesie Bewusstlosigkeit, Bewegungslosigkeit und Amnesie werden aufgegriffen und möglichen anatomischen Zielen zugeordnet.


Narkosemechanismen Ionenkanäle Isofluran Propofol Ketamin 

What do we know about anesthetic mechanisms?

Hypnosis, unresponsiveness to surgical incision and amnesia


Despite the increase of molecular knowledge in anesthesia research over the past decades there is still ongoing discussion about the mechanisms of anesthesia. This article focuses on presenting anesthetic sensitive ligand and voltage gated ion channels. The impact on anesthetic modulated ion channels is summarized for clinically commonly used anesthetics isoflurane, propofol and ketamine. Furthermore, the anesthetic features hypnosis, unresponsiveness to surgical incision and amnesia and their putative relevant anatomical sites in the central nervous system are briefly introduced.


Mechanisms of anesthesia Ion channels Isoflurane Propofol Ketamine 


  1. 1.
    Alkire MT, Haier RJ, Fallon JH (2000) Toward a unified theory of narcosis: brain imaging evidence for a thalamocortical switch as the neurophysiologic basis of anesthetic-induced unconsciousness. Conscious Cogn 9:370–386CrossRefPubMedGoogle Scholar
  2. 2.
    Alkire MT, McReynolds JR, Hahn EL, Trivedi AN (2007) Thalamic microinjection of nicotine reverses sevoflurane-induced loss of righting reflex in the rat. Anesthesiology 107:264–272CrossRefPubMedGoogle Scholar
  3. 3.
    Anis NA, Berry SC, Burton NR, Lodge D (1983) The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 79:565–575PubMedGoogle Scholar
  4. 4.
    Anker-Møller E, Spangsberg N, Arendt-Nielsen L et al (1991) Subhypnotic doses of thiopentone and propofol cause analgesia to experimentally induced acute pain. Br J Anaesth 66:185–188CrossRefPubMedGoogle Scholar
  5. 5.
    Antognini JF, Schwartz K (1993) Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology 79:1244–1249PubMedGoogle Scholar
  6. 6.
    Barann M, Dilger JP, Boenisch H et al (2000) Inhibition of 5-HT3 receptors by propofol: equilibrium and kinetic measurements. Neuropharmacology 39:1064–1074CrossRefPubMedGoogle Scholar
  7. 7.
    Bayliss DA, Barrett PQ (2008) Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact. Trends Pharmacol Sci 29:566–575CrossRefPubMedGoogle Scholar
  8. 8.
    Carlà V, Moroni F (1992) General anaesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex. Neurosci Lett 146:21–24CrossRefPubMedGoogle Scholar
  9. 9.
    Chen X, Shu S, Bayliss DA (2009) HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine. J Neurosci 29:600–609CrossRefPubMedGoogle Scholar
  10. 10.
    Chen X, Shu S, Kennedy DP et al (2009) Subunit-specific effects of isoflurane on neuronal Ih in HCN1 knockout mice. J Neurophysiol 101:129–140CrossRefPubMedGoogle Scholar
  11. 11.
    Chen X, Sirois JE, Lei Q et al (2005) HCN subunit-specific and cAMP-modulated effects of anesthetics on neuronal pacemaker currents. J Neurosci 25:5803–5814CrossRefPubMedGoogle Scholar
  12. 12.
    Chortkoff BS, Eger EI 2nd, Crankshaw DP et al (1995) Concentrations of desflurane and propofol that suppress response to command in humans. Anesth Analg 81:737–743CrossRefPubMedGoogle Scholar
  13. 13.
    Chortkoff BS, Gonsowski CT, Bennett HL et al (1995) Subanesthetic concentrations of desflurane and propofol suppress recall of emotionally charged information. Anesth Analg 81:728–736CrossRefPubMedGoogle Scholar
  14. 14.
    Eger EI 2nd, Saidman LJ, Brandstater B (1965) Minimum alveolar anesthetic concentration: a standard of anesthetic potency. Anesthesiology 26:756–763PubMedCrossRefGoogle Scholar
  15. 15.
    Flood P, Ramirez-Latorre J, Role L (1997) Alpha 4 beta 2 neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha 7-type nicotinic acetylcholine receptors are unaffected. Anesthesiology 86:859–865CrossRefPubMedGoogle Scholar
  16. 16.
    Franks NP (2008) General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci 9:370–386CrossRefPubMedGoogle Scholar
  17. 17.
    Grasshoff C, Drexler B, Rudolph U, Antkowiak B (2006) Anaesthetic drugs: linking molecular actions to clinical effects. Curr Pharm Des 12:3665–3679CrossRefPubMedGoogle Scholar
  18. 18.
    Grasshoff C, Rudolph U, Antkowiak B (2005) Molecular and systemic mechanisms of general anaesthesia: the „multi-site and multiple mechanisms“ concept. Curr Opin Anaesthesiol 18:386–391CrossRefPubMedGoogle Scholar
  19. 19.
    Hales TG, Lambert JJ (1991) The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones. Br J Pharmacol 104:619–628PubMedGoogle Scholar
  20. 20.
    Harrison NL, Kugler JL, Jones MV et al (1993) Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane. Mol Pharmacol 44:628–632PubMedGoogle Scholar
  21. 21.
    Jinks SL, Bravo M, Hayes SG (2008) Volatile anesthetic effects on midbrain-elicited locomotion suggest that the locomotor network in the ventral spinal cord is the primary site for immobility. Anesthesiology 108:1016–1024CrossRefPubMedGoogle Scholar
  22. 22.
    Joksovic PM, Bayliss DA, Todorovic SM (2005) Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane. J Physiol 566:125–142CrossRefPubMedGoogle Scholar
  23. 23.
    Joksovic PM, Brimelow BC, Murbartián J et al (2005) Contrasting anesthetic sensitivities of T-type Ca2+ channels of reticular thalamic neurons and recombinant Ca(v)3.3 channels. Br J Pharmacol 144:59–70CrossRefPubMedGoogle Scholar
  24. 24.
    Krasowski MD, Harrison NL (1999) General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci 55:1278–1303CrossRefPubMedGoogle Scholar
  25. 25.
    Lin LH, Chen LL, Zirrolli JA, Harris RA (1992) General anesthetics potentiate gamma-aminobutyric acid actions on gamma-aminobutyric acid A receptors expressed by Xenopus oocytes: lack of involvement of intracellular calcium. J Pharmacol Exp Ther 263:569–578PubMedGoogle Scholar
  26. 26.
    Lyashchenko AK, Redd KJ, Yang J, Tibbs GR (2007) Propofol inhibits HCN1 pacemaker channels by selective association with the closed states of the membrane embedded channel core. J Physiol 583:37–56CrossRefPubMedGoogle Scholar
  27. 27.
    MacDonald JF, Bartlett MC, Mody I et al (1991) Actions of ketamine, phencyclidine and MK-801 on NMDA receptor currents in cultured mouse hippocampal neuron. J Physiol 432:483–508PubMedGoogle Scholar
  28. 28.
    Mashour GA, Forman SA, Campagna JA (2005) Mechanisms of general anesthesia: from molecules to mind. Best Pract Res Clin Anaesthesiol 19:349–364CrossRefPubMedGoogle Scholar
  29. 29.
    Minami K, Wick MJ, Stern-Bach Y et al (1998) Sites of volatile anesthetic action on kainate (glutamate receptor 6) receptors. J Biol Chem 273:8248–8255CrossRefPubMedGoogle Scholar
  30. 30.
    Orser BA, Bertlik M, Wang LY, MacDonald JF (1995) Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones. Br J Pharmacol 116:1761–1768PubMedGoogle Scholar
  31. 31.
    Orser BA, Wang LY, Pennefather PS, MacDonald JF (1994) Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons. J Neurosci 14:7747–7760PubMedGoogle Scholar
  32. 32.
    Pasternak T, Greenlee MW (2005) Working memory in primate sensory systems. Nat Rev Neurosci 6:97–107CrossRefPubMedGoogle Scholar
  33. 33.
    Patel AJ, Honoré E, Lesage F et al (1999) Inhalational anesthetics activate two-pore-domain background K+ channels. Nat Neurosci 2:422–426CrossRefPubMedGoogle Scholar
  34. 34.
    Perez-Reyes E (2002) Molecular physiology of low-voltage-activated T-type calcium channels. Physiol Rev 83:117–161Google Scholar
  35. 35.
    Putzke C, Hanley PJ, Schlichthörl G et al (2007) Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1. Am J Physiol Cell Physiol 293:1319–1326CrossRefGoogle Scholar
  36. 36.
    Rampil IJ (1994) Anesthetic potency is not altered after hypothermic spinal cord transection in rats. Anesthesiology 80:606–610CrossRefPubMedGoogle Scholar
  37. 37.
    Rampil IJ, Mason P, Singh H (1993) Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology 78:707–712CrossRefPubMedGoogle Scholar
  38. 38.
    Ranft A, Kurz J, Deuringer M et al (2004) Isoflurane modulates glutamatergic and GABAergic neurotransmission in the amygdala. Eur J Neurosci 20:1276–1280CrossRefPubMedGoogle Scholar
  39. 39.
    Rebecchi MJ, Pentyala SN (2002) Anaesthetic actions on other targets: protein kinase C and guanine nucleotide-binding proteins. Br J Anaesth 89:62–78CrossRefPubMedGoogle Scholar
  40. 40.
    Rudolph U, Antkowiak B (2004) Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci 5:709–720CrossRefPubMedGoogle Scholar
  41. 41.
    Sanders RD, Patel N, Hossain M et al (2005) Isoflurane exerts antinociceptive and hypnotic properties at all ages in Fischer rats. Br J Anaesth 95:393–399CrossRefPubMedGoogle Scholar
  42. 42.
    Simon W, Hapfelmeier G, Kochs E et al (2001) Isoflurane blocks synaptic plasticity in the mouse hippocampus. Anesthesiology 94:1058–1065CrossRefPubMedGoogle Scholar
  43. 43.
    Smith C, McEwan AI, Jhaveri R et al (1994) The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. Anesthesiology 81:820–828CrossRefPubMedGoogle Scholar
  44. 44.
    Solt K, Forman SA (2007) Correlating the clinical actions and molecular mechanisms of general anesthetics. Curr Opin Anaesthesiol 20:300–306CrossRefPubMedGoogle Scholar
  45. 45.
    Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscillations in the sleeping and aroused brain. Science 262:679–685CrossRefPubMedGoogle Scholar
  46. 46.
    Todorovic SM, Perez-Reyes E, Lingle CJ (2000) Anticonvulsants but not general anesthetics have differential blocking effects on different T-type current variants. Mol Pharmacol 58:98–108PubMedGoogle Scholar
  47. 47.
    Yamakura T, Chavez-Noriega LE, Harris RA (2000) Subunit-dependent inhibition of human neuronal nicotinic acetylcholine receptors and other ligand-gated ion channels by dissociative anesthetics ketamine and dizocilpine. Anesthesiology 92:1144–1153CrossRefPubMedGoogle Scholar
  48. 48.
    Yamakura T, Sakimura K, Shimoji K, Mishina M (1995) Effects of propofol on various AMPA-, kainate- and NMDA-selective glutamate receptor channels expressed in Xenopus oocytes. Neurosci Lett 188:187–190CrossRefPubMedGoogle Scholar
  49. 49.
    Ying SW, Abbas SY, Harrison NL, Goldstein PA (2006) Propofol block of I(h) contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons. Eur J Neurosci 23:465–480CrossRefPubMedGoogle Scholar
  50. 50.
    Zhang L, Oz M, Stewart RR et al (1997) Volatile general anaesthetic actions on recombinant nACh alpha 7, 5-HT3 and chimeric nACh alpha 7-5-HT3 receptors expressed in Xenopus oocytes. Br J Pharmacol 120:353–355CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2009

Authors and Affiliations

  • V.-S. Eckle
    • 1
    • 2
  • C. Hucklenbruch
    • 1
    • 3
  • S.M. Todorovic
    • 1
  1. 1.Department of AnesthesiologyUniversity of VirginiaCharlottesville, VAUSA
  2. 2.Klinik für Anaesthesiologie, Klinikum rechts der IsarTechnische Universität MünchenMünchenDeutschland
  3. 3.Klinik und Poliklinik für Anästhesiologie und operative IntensivmedizinUniversitätsklinikum MünsterMünsterDeutschland

Personalised recommendations