title: Opposing actions of sevoflurane on GABAergic and glycinergic synaptic inhibition in the spinal ventral horn.
abstract: BACKGROUND
  The ventral horn is a major substrate in mediating the immobilizing properties of the volatile anesthetic sevoflurane in the spinal cord. In this neuronal network, action potential firing is controlled by GABA(A) and glycine receptors. Both types of ion channels are sensitive to volatile anesthetics, but their role in mediating anesthetic-induced inhibition of spinal locomotor networks is not fully understood.
  
  
  RESULTS
  To compare the effects of sevoflurane on GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) whole-cell voltage-clamp recordings from ventral horn interneurons were carried out in organotypic spinal cultures. At concentrations close to MAC (minimum alveolar concentration), decay times of both types of IPSCs were significantly prolonged. However, at 1.5 MAC equivalents, GABAergic IPSCs were decreased in amplitude and reduced in frequency. These effects counteracted the prolongation of the decay time, thereby decreasing the time-averaged GABAergic inhibition. In contrast, amplitudes and frequency of glycinergic IPSCs were not significantly altered by sevoflurane. Furthermore, selective GABA(A) and glycine receptor antagonists were tested for their potency to reverse sevoflurane-induced inhibition of spontaneous action potential firing in the ventral horn. These experiments confirmed a weak impact of GABA(A) receptors and a prominent role of glycine receptors at a high sevoflurane concentration.
  
  
  CONCLUSIONS
  At high concentrations, sevoflurane mediates neuronal inhibition in the spinal ventral horn primarily via glycine receptors, and less via GABA(A) receptors. Our results support the hypothesis that the impact of GABA(A) receptors in mediating the immobilizing properties of volatile anesthetics is less essential in comparison to glycine receptors.
authors.affiliation: Experimental Anesthesiology Section, Department of Anesthesiology & Intensive Care, Tübingen University Hospital, Eberhard-Karls-University, Tübingen, Germany.
authors.forename: Veit-Simon
authors.initials: VS
authors.lastname: Eckle
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hauser
authors.forename: Berthold
authors.initials: B
authors.lastname: Drexler
authors.forename: Bernd
authors.initials: B
authors.lastname: Antkowiak
authors.forename: Christian
authors.initials: C
authors.lastname: Grasshoff
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D011247:Pregnancy; D011963:Receptors, GABA-A / Q000378:metabolism*; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077149:Sevoflurane; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D058787:GABA-A Receptor Antagonists; D008738:Methyl Ethers; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D000077149:Sevoflurane
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