Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats.
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Grasshoff C, Antkowiak B
Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats.
Br J Anaesth. 2006 Nov;97(5):687-94. doi: 10.1093/bja/ael239. Epub 2006 Sep 13.
- PubMed ID
- 16973644 [ View in PubMed]
- Abstract
BACKGROUND: Volatile anaesthetics are widely used agents in clinical anaesthesia, although their mechanism of action is poorly understood. In particular, the dominant molecular mechanisms by which volatile anaesthetics depress spinal neurones and thereby mediate spinal effects such as immobility have recently become a matter of dispute. As GABAA and glycine receptors are potential candidates we investigated the impact of both receptor systems in mediating the depressant effects of isoflurane and enflurane on spinal neurones in rats. METHODS: The effects of isoflurane and enflurane on spontaneous action potential firing were investigated by extracellular voltage recordings from ventral horn interneurones in cultured spinal cord tissue slices obtained from embryonic rats (E 14-15). RESULTS: Isoflurane and enflurane reduced spontaneous action potential firing. Concentrations causing half-maximal effects (isoflurane: 0.17 mM; enflurane: 0.50 mM) were less than EC50-immobility (isoflurane: 0.32 mM; enflurane: 0.62 mM). Effects of isoflurane were mediated by 39% by glycine receptors and 36% by GABAA receptors. The effects of enflurane were mediated 26% by GABAA receptors and 29% by glycine receptors. CONCLUSION: These results demonstrate that the effects of isoflurane and enflurane on GABAA and glycine receptors contribute almost equally to their depressant actions on spinal ventral horn neurones in rats. The fraction of inhibition mediated by both receptor systems differs between specific volatile anaesthetics. Our data argue against the theory that a dominant molecular mechanism accounts for spinal effects of volatile anaesthetics.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Desflurane Glycine receptor subunit alpha-1 Protein Humans YesAgonistDetails Enflurane GABA(A) Receptor (Protein Group) Protein group Humans YesPotentiatorDetails Enflurane Glycine receptor subunit alpha-1 Protein Humans YesPotentiatorDetails Isoflurane Glycine receptor subunit alpha-1 Protein Humans YesAgonistDetails